ANTI-G SUIT INFLATION EFFECTS DURING LOW-INTENSITY -/ + GZ MANEUVERS. Michael Nicholas Colapinto

Transcription

1 ANTI-G SUIT INFLATION EFFECTS DURING LOW-INTENSITY -/ + GZ MANEUVERS Michael Nicholas Colapinto A thesis submitted in conformi ty wi th the requirements for the degree of Master of Science Gradua te Department of Community Heal th University of Copyright by Michael Nicholas Colapinto 2000

2 National Library 1*1 ofcamda uisitions and abgraph'isentices BiMiiue nationale du Canada Acquisitions et setvices bibliognphiqws The author has granted a nonexchsive Licence dowing the National Library of Canada to reproduce, loan, distnbute or sel1 copies of this thesis in microform, papa or electronic formats. The author retains ownership of the copyright in this thesis. Neither the thesis nor substantial extracts fiom it may be ptinted or otherwise reproduced without the author's permission. L'auteur a accorde me Licence non exclusive permettant a la BibliotMque nationale du Cmada de reproduire, prêter, distribuer ou vendre des copies de cette thèse sous la forme de microfiche/nlm, de reproduction sur papier ou sur format électronique. L'auteur consene la proprieté du droit d'auteur qui protège cette thèse. Ni la thèse ni des extraits substantiels de celle-ci ne doivent être imprimes ou autrement reproduits sans son autorisation.

3 Abstract ANTI-G SUIT INFLATION EFFECTS DURLNG LO W-INTENSITY -/+ GZ MANEUVERS For the dcgree of Master of Science, 2000 Michxi Nicholas Colapinto Graduate Depart ment of Community Hdth University of Toronto Purpose: It was hypothesized that early initiation of G-suit inflation with increased pressure and rate would offer greater protection agaïnst the hypotensive response ("push- pull effect". PPE) resulting from -/+Gz transitions ("push-pull effect maneuver", PPEM) venus the existing inflation schedule. Methods: Using a tilt table, subjects were rapidly tilted from HUTL (15' from vertical; +l Gz) to HDT (135'; Gz for 15 secs) to HUT2(1S0. for45 secs). Physiological measurements for 1 unprotected and 4 protection schedules were analyzed. Resulîs: Al1 G-suit schedules maintained b l d pressure suggesting inflation is an adequate protecti ve measure during low-intensi ty PPEMs. Few statisticall y signi ficant differences were observed between the protection schedules. Conclusions: (1) G-suit inflation arneliorated the hypotensive response to the PPEM, (2) Results were not conclusive as to whether inflations of certain timing or pressure will further melionte this hypotensive response. An inmased G-envelope and operationally proper inflation pressures are recomrnended for futun investigations.

4 Acknowledgements There are so many people that 1 would Iike to thank for both direct and indirect involvement in the successful completion of this thesis. Fint and foremost, 1 must thank my supervisor, Dr. Len Goodman. 1 cm not express how important his guidance was to me. If you are one of his future students reading this thesis. consider younelf lucky to have such a kind, helpful, intelligent, and congenial mentor. 1 would also like to thank my fellow students Paul Handley, Carmen Hertzenkg, Tim Mandzak, and Farheen Rashid, dong with Capt. Helen Wright and 2Lt. Victor Mota, for king there for a chat, a joke, or even the odd compiiiint; not that 1 was bitter or anything. (1 apologize to those who do not understand the previous staternent. Along with the terms "Scowley" and "Sideshow" it is an inside joke). I must also thank the subjects who partook in this experiment. Without you, this would not have been possible. Thankî goes to Jim Maloan and Ted h o n for their invaluable technical expertise as well as Vahid Askan, Bill Fraser, and the entire ALSS and SAILSS groups for their assistance. 1 would especially like to thank Tom Gee for his help with the UNM programs (some day I'm going to ask him how the heck he understands this stuff!) md Macella Maxwell for providing me with wonderful colour slides for my defence. My thanks is also extended to Pierre Turgeon for his assistance with the barocuff (my original project) and for ensuring that 1 was never zapped once by the radiofrequency sealer. A special thank you to Gary Macpherson for allowing me to use the garage gyrn and, therefore, enabling me to keep my sanity. 1 must also thank Bill Martel1 for keeping me hydrated and fed and DMig Vaughn for sponing me in the weight mm, 1 iii

5 would aiso like to thank the people that originally got me involved at DCIEM as a test subject. Dr. Stephen Cheung, Dr. Tom McLellan. Jan Pope. and Doug Bell. Thank you for sparking my interest in huma. physiologicd research. 1 would like to thank my fnends David Cherry. Roger Near, Mark Borthwick. Mark Balaban, Briget Belton. Paul Bailey. and Erin Harris, dong with the entin Centm Valet stalf including Jeff Ross. Mike Milosh. and Jason Woolmer. Over the past two and a half years. you have al1 at one point (or more) asked me what exactly 1 was doing. Thank you for listening to me. nodding your head. and appearing interested even though you were most likely wishing 1 would just shut up. 1 would also like to thank my Grandmother Katherine Finnerty and Mr. John O'Halloran. These two people pnyed for me on alrnost a daily basis. 1 am not a religious man but 1 can not help but think that in some imperceptible way this made an incredible di fference. Finaily, 1 would like to thank the most important people in the world to me. To my sisters Kimberly, Cynthia. and Nicole: 1 do not Say this often enough but 1 love you and am proud that you nre my siblings. To my parents Dr. Nicholas Colapinto and Margaret Colapinto: Your interest. support, and caring throughout my life and education has been incredible. You aiways put me and my interests ahead of youn. You instilled in me a hard work ethic and the belief that 1 could achieve anything as long as 1 put my rnind to it. For al1 this and more, you mean so much to me. 1 love you both.

6 Table of Contents 23 The physiologkd effkct of exposure to +Gz oo.oo~o~oo~ou~ooo~ooo~ooooeowwew~ooeooooeoooeoooooooooeoooooooooo Hydrostatic effect. caused by increased +Gz Importance of +Gr-induced HLBP changes Hydrostiitic effects of -Gz and the effect of -Gr on HLBP Tilt table test for the push-pull effect ~ o~~o~~oooo~o~o~~~ooo~oeo~eoo~~oooooooo~~o~oooo~ooou~oouo~oo~o~ooummw~~eoouooooo Advantages of the tilt table simulation of the PPEM Disadvantages of the tilt table simulation of the PPEM Current countermqamns o~-we*wo.onoe"n.noowotoeeooomooooho.eomooooo..oooeoooooooooooeoooeooowooeooo*eeooooooeosoeeoooooooh* Extendecl Coverage G-suits..., The control of G-suit inflation by the G-valve: timing and rate of inflation Use of *e anti-g suit for protection against the push-pull effect The development of an electronic 'srniut' G-valve for protection ûgninst the push-pull effect... 18

7 33 Tut table test for the push-pull eplmt m..... m ~ ~ ~ o ~ ~ m ~ ~ ~ ~ ~ C I ~ ~ m ~ m 39 ~ ~ ~ ~ e ~. ~ ~ n Review of tilt table acceleration remch Why the tilt-table G-reserirch gap of over 30 yem'? The tilt table as a method for examining the push-pull effect Review of the tilt table simulation of the push-pull effect maneuver AntLG dt 35.1 The G-suit inflation during tilt Modem G-suit design developments ee...n...~~o*~~~~*~eu~*~~~*~~~~.**m*~***~****~o*****~.to.t~n*mw**~~m~n~~*~"~*~~.~***~o*.**e**.~~~ G-suit inflation: timing and rate of inflation Use of the Anti-G suit for protection against the push-pull cffect maneuver Subjects.t.e.H.~.~.u.~.H.n.~.,~.~e.m.o.m.~.~.o.~ 54.nHt.o.t.e~ Recruitment Subject Training Subject restrictions Subjwt characteristics Physiological monitoring and instrumentation.,.,.e.~.~.~.e.,.i.t.~.e Blood pressure...~...~...~ Systolic and diastolic blood pressure Mean arterial blood pressure..., Head-lcvel blood pressure ( WLBP) Hewt rate Impedance cwdiogrriphy Venous Occlusion Plethysmogmphy Subjective mepsu~menls,...~...-.*.* Visual ligfit loss...., Other subjective measuremtnts... 6) 4.4 Equipment..u.w...n...~ ~ ~ o H e ~ e ~ e " ~ ~ ~ ~ ~ n ~ ~ e M ~ ~ H ~ ~ ~ ~ ~ ~ ~ 65 ~ ~ ~ " o ~ ~ ~ ~ ~ Tilt table Anti-G suit and pressure delivery system Ihlb AWym..e...n..~~.~~.~n~.u~mmrn-~~~*mt.~~~~~*w~w..~~~~.*~~e~~~~~~~~~~*~~~m~~w~~w.rten~n..e o."o"rn dp and dt for Systolic Blood Pressure (SBP) SBP. MAP. HLBP. HR. Zo. SI. CI. TPRi. FBF. ruid FVR Re-anrilysis..., ,, Sysîok... B. ld.. Pressure Deamse in SBP (dp).., , Tie of SBP recovery (dt)...,,...~.~...,~~..~~~~...~.~...,...

8 5.2.3 Repeated mesures ANOVA for percent change in SBP Insight into the cardiovascular respoiise to the PP EhZ.~.m..,...,-.mm~m~~~m~~~~ Cardiovascular efftcts of HDT for the unprotected schcduie , The cardiovsiscular effects of subsequent HUT during unprotecteâ runs n"~ohoomuhoh..oooo.h~~.m The etlit otg-suit inflation upon the physiologie mponses to tbe PPEM,,.,,,.mm, The acute effects of G-suit inflation The tffect of Ci-suit inflation ovcr time... CC.CC.C~CC... C.~C.C.C.C The efiect of vwying the timing and pressure of G-suit inflation C ~ ~ ~ ~ I ~ ~ m - n w u o o - ~ m - o m ~ - m m. r + t. r - ~ m m o m m ~ o m o m o m o m m o o o - o o m ~ o ~ m m m - ~ m o m o o m m m ~ ~ m ~ - m m t - m ~ m o ~ n m u ~ m ~ tmplications for operations. future rcsearch, and the dcvelopment of an optimd protection systern..., Conclusions brrsed upon nul1 hypotheses...-,.,.,., md schedule versus the PPE.,..., e.. vii

9 List of Tables TABLE 2-1 EXPLANATION OF G-SUIT INFLATION SCHEDULES TABLE 4-1 SUMMARY OF PHYSIOLOGICAL MEASUREMENTS. TECHNIQüES. AND INSTRüMENTATION TABLE 4-2 TILT TABLE PROFILE AND EXPERIMENTAL SCHEDULES...,., TABLE 5-1 SUBJECT CHARACTERISTICS

10 List of Figures FI4 GURF, 2-1 ANGULAR VELOCITY DURING FLIGHT... 5 FI4 CURE 2-2 TERMINOLOGY FOR ACCELERA'TION FORCES ON THE BODY FI( GURE 2-3 REFLEX MECHANISMS FOR COPING WITH P O S m AND NEGATIVE GZ FlI CURE 24 (A) G-TIME TOLERANCE CURVE (B) EFFECT OF G-ONSET ON G TOLERANCE FII GURE 2-5 TILT TABLE PROFILE WTH EXPERIMENTAL SCHEDULES FI( GURE 3-1 SCHEMATIC OF SYSTOUC BLOOD PRESSURE IN 'ME SUPiNE AND ERECT POSIIION AT +1 GZ GU= $2 THE PUSH-PUU EFFECT GURE 4-1 DATA COLLECTION CURE 5-1 DECREASE IN SBP (DP)......* SURE 5-2 TCME OF SBP RECOVERY (Dm SURE 5-3 PERCENT CHANGE IN SBP SU RI PERCENT W G E IN MAP SURE 5-5 PERCENT CHANGE N HLBP CURE S 4 PERCENT CHANGE IN HR SURE 5-7 PERCENT CHANGE IN SURE 5-8 PERCENT CHANGE IN SI SURE 5-9 PERCENT CHANGE IN CI SURE 5-10 PERCENT CHANGE IN TPRI SURE 5-11 PERCENT CHANGE in FBF SURE 5-12 PERCENT CHANGE IN FVR

11 List of Appendices APPENDIX A S AMPLE RECORDiNGS APPENDIX B ANOV A RESULTS APPENDIX C MEANS TABLES APPENDIX O CONSENT FORM APPENDIX E FBF SAMPLE MEASUR APPENDCX F G-SUIT APPARATUS/EXPERMENTAL SETUP APPENDIX G INTER-SUBJECT COMPAlUSION OF ABSOLUTE CHANGES IN SBP. HLBP. AND HR

12 1.0 Introduction Recent studies have shown that if a pilot experiences a period of -Gz directly preceding a +Gz maneuver, G-tolerance may be impaired [LI. This phenornenon ha been tenned the 'push-pull' effect 12). In studies conducted by the Canadian and United States Air Forces concluded that the push-pull effect (PPE) has ken a contributing factor in numerous mi litiuy ainraft accidents [3-51. These studies implicated push-pull mediated impairnent of G-tolennce as a major nsk to pilot performance that could ultimately lead to aircrew injury andor death. Thus, it is important to leam more about -Gz to +Gz maneuvea (known as the push-pull effect maneuver or PPEM) and develop methods to protect pilots rgainst the PPE that these maneuvers induce. Although the basic physiological responses that occur during the PPEM have been described, a detailed mechanistic understanding is still incomplete since opparatus used to study the physiological effects of push-pull make complex measurements difficult. Most centrifuges. a common investigative tml in acceleration nserirch, cannot perform the -Gz accelerations necessary to mirnic the PPEM. ln-flight measurements are also limited by practical constraints, since only certain monitoring equipment is feasible in the cockpit environment,

13 The tilt table is the most recent experimental tool used to study the PPE. The tilt table has been used in orthostatic hypotension msearch for numemus years and has been successfully implemented in numemus cwdiovascular and acceleration studies ]. The tilt table is a rotating bed that cm be tilted at various angles around its centre point. A subject. secured to the table in a supine or seated position. cm be tilted at specific angles. B y subjecting a person to a head-up tiit (HUT) to head-down tilt (HDT) to HUT sequence. the tilt table cm reproduce a low-intensity PPEM and its corresponding physiological nsponse with the added advantage of pater control over the testing environment. Monitoring equipment that cannot be used for in-flight studies due to size and feasibility constnints can be readily applied in the tilt table lab [SI. In addition to mimicking the physiological changes caused by the PPEM. the tilt table also provides an opportunity for testing countemeasure equipment, such as the anti- G suit. Although G-suit inflation in high +Gz situations has been studied thoroughly. very little is known about the effect of the G-suit upon the PPE. G-suit inflation is a known method for maintaining blood pressure at head-level and increasing G-tolerance. however, the initiation of inflation, the onset rate and the pressure at which the G-suit should be inflated dunng the PPEM to counteract the PPE is still unknown. This investigation will attempt to elucidate these concems by using the low-intensity tilt table PPEM while exposing human volunteers to various G-suit inflation scheduks. G-suit inflation will be initiated at different times dunng the tilt maneuver to detennine if the onset of inflation and/or the maximum inflation pressure has an effect on protection against the PPE.

14 This research will provide insight into the cdovascular regulatory pmcesses involved in the PPE and will contribute to the development of an effective PPEM protection schedule. This schedule could then be further evaluated in a high-g PPEM environment before becoming operational. Hopefully, this schedule will be used in the future to better pmtect pilots against the PPE, ultimately saving aircrew hm potential injury andor loss of life.

15 2.0 Background 2.1 Physics involved in military tactical aviation Newton's Second Law of Motion States that the magnitude of an object's accelention is directly pmportional to the magnitude of the net force and inversely proportional to the object's mas: Equation 2-1 Where F is force in Newtons (N), m is the mass of the object in kilograms (kg), and a is the accelention in metres per second per second (ms-2) [13]. Since mas is a constant, only changes in acceleration cm alter the magnitude of the force exerted on an object. Equation 2-1 can be modified for centripetal accelerations, accelerations that are conunonly expenenced during military tactical aviation. Centripetal acceleration is equd to the square of the angular velocity multiplied by the radius of the object to the centre of rotation. Thus:

16 Equation 2-1 b Where u2 is the square of the angular velocity and r is the radius of the object to the centre of rotation. The angular velocity during flight is illustrated in Figure 2-1: Figure 2-1 Angular velwity during flight w O O O O -pdh velocdy H.. circunferwrid vebcdy (v) (w) 1 1 adapted from [14] In acceleration research, the magnitude of an applied accelention is often expressed in tenns of the Earth's standard acceleration due to gravity, 9.8 mr2. if this value is used as a denominatot, the acceleration applied to an object can be expressed relative to the stanâmi acceleration of gravity in units of O:

17 Equation 2-2 applied acceleration in ms-' G= std. accelention of gravity (9.8 ms-') Since it is a vector quantity. acceleration not only has magnitude but direction as well. Using Newton's Third Law of Motion that every action has an equal and opposite reaction, standard acceleration nomenclature defines +Gz as a gravito-inertial reaction in the direction of the feet in opposition to a headward acceleration. Using the same methodology, -Gz is defined as a gravito-inenial reaction in the direction of the head as a result of a footward acceleration. Figure 2-2 illustrates standard acceleration nomenclature across 3 axes: Figure 23 Te~ology for accelemtion forces on the body adapted h m 1151

18 22 The physiological effeet of expure to +Gz Most heaithy individuals cm cope with the effects of +L Gz without difficulty. However. symptoms of cardiovascular insufficiency arise in situations such as milit* tactical aviation when pilots perfom banked tums, dives. and pull-outs which result in varied centripetal accelerations and gravito-inertial forces. Forces other than +l Gz cause relative changes in the hydrostatic foms within al1 vessels in the circulatory system. These changes can have many deletenous effects ranging from Mnor visual distuhances to the possibility of loss of consciousness [L4]. If1 Hydrostatic effkts caused by +Gz Gravito-inenid forces act not only on the body but the blood in the vasculature as well, +Gz causes blood to shift in the footwd direction. Due to the elastic nature of the venous circulation, this results in passive dilation of the lower vasculature and an inmeose in blood volume, blood flow, and blood pressure in the lower limbs. Since there is an increase in blood volume below heart level, there is less blood in the vasculature above hem level. This results in the decreased diameter of upper vasculature and, therefore, decreased bld flow and blood pressure above the heart. Ultimately. this leaàs to a decrease in head-level blood pressure (HLBP).

19 2.23 Importance of +Gz-induced HLBP changes Changes in HLBP caused by ffiz are of great interest and importance. Decreased HLBP effects the perfusion of the eyes and the brain, two vital organs during flight. Any loss of vision or decrease in cognitive ability could drastically effect pilot cornpetence and put aircrew at risk for injury andor death. Therefore. in an effort to dirninish this risk, numerous studies have been perfomed to leam more about the effects of +Gz and its effect on HLBP. At +l Gz, HLBP is approximately 98 mmhg. This is more than enough pressure for adequate visual and cognitive function. However, as gravito-inertial force increases beyond +L Gz, blood flow to the head is compromised. This results in a decrease in HLBP at a rate of approximately 22 mmhg per G. Therefore, at +4 Gz, HLBP decreases to approximately 32 mmhg effecting retinai blood flow. This resulis in a loss of peripheral vision (greyoui). At +5 Gz, HLBP is approximately 10 mm Hg which leads to i complete lack of ocular perfusion. The result is a complete loss of vision (blackout). At +5.5 Gz, HLBP is approximately O rnmhg. Since there is no blood pressure at head-level. the brain is no longer perfused. This ultimately leads to in gnvity induced loss of consciousness (G-LOC) Hydmtaüc effeets of -Gz and the effet of -Gz on HLBP -Gz pmduces a blood shifi in the headward direction. This inmase in blood flow above heart-level causes HLBP to inmase at rate of approximately 22 mmhg per G.

20 Therefore, at -3 Gz. HLBP is approximately 186 mmhg, at -4 Gz, 208 mmhg, and so on. This translocation of fluid to the head is very unpleasant experience since it results in extensive facial edema. breathing difficulties, and possible disorientation. It may be postulated that a -3 to -4 Gz increase would result in cerebral vesse1 rupture and brain hemorrhaging. However, this does not occur. During -Gz. the increase in vascular pressure in the brin is bdsuiced by similar incnlses in cerebrospinal fluid pressure. Therefore. the nsk of rupture is minimal. Nonetheiess. -Gz remains an uncornfortable experience. 2.3 Reflex mechanisms for coping with positive and negative Gz The deleterious effects caused by +Gz and -Gz exposun described in the previous two sections are the result of the inability of the cardiovascular system to cope with increased hydrostatic forces and, therefore, maintain HLBP [16]. When arterial pressure fluctuates, the cardiovascular reflexes are invoked in an attempt to sustain HLBP. The carotid baroreceptors. dong with the cardio-pulmonuy baroreceptors of the aortic arch and other less undentwd sensors throughout the cardiovûscular system, are al1 part of this neurological reflex mechanism. The carotid bmreceptoa indirectly monitor HLBP by sensing changes in cacotid artery diameter due to alterations in blood flow to the head. If a pilot is exposed to +Oz, HLBP begins to decrease. The carotid baroreceptors sense this change and act to increase arterial blood pressure in an attempt to maintain

21 HLBP (known as the baroreflex). This reflex triggers an increase in hem rate (ER) and vasoconstriction. This is done in an effort to protect against the visual disturbances and G-LOC associated with increased +Gz. If exposed to -Gz and HLBP beings to increûse. the baroreflex causes a decrease in HR and vasodilation in an attempt to decrease HLBP back towards normal levels. Under -Gz, the bamreflex mainly acts to limit the amount of uncomfortiible fidcicial edema, breathing difficulties, and symptoms of disorientation associated with the translocation of blood to the head and chest. Figure 2-3 sumrnarizes the rrfiex mechanisms for coping with both positive and negative Gz: Figure 2.3 ARTERIAL PRESSURE Artarial Barorocoptor Meduila Cardiavarculai Nuclai 1 He8n Rata Cardkc Output (aiow sacs) C Vascuiar Rosistanca Reflex mechanisms for caping with positive and negative Gz aâapted h m [17]

22 2.4 The effeet of +&-onset rate and duration at higb +Gz G-onset rate and G-duntion also have an effect upon G-tolerance. As illustrated in Figure Ma, the cardiovascular reflexes are best able to defend against short durations of ffiz. If the length of G-exposure is minimal. the body is protected by a 5 second oxygen reserve in the brain. Therefore, there is littie risk of G-LOC even if cerebral perfusion and XLBP are significantly diminished. If G-exposure is sustained. the carotid barorenex will attempt to countenct the decrease in HLBP but. after a pend of time, will eventually Fil. The body is simply not able to defend itself against such a severe. sustained, low HLBP situation. As illustrated in Figure Wb. the body is also effective in defending itself against graduai-onset Gz exposure. A graduai-onset rate gives the cardiovascular reflexes time to react to the exposure to G. Thus. up to n point (usually +4 to 5.5 Gz) the body has an opportunity to counteract the effects of the increased Gz conditions. The barorefiex reacts tw slowly to defend itself against rapid-onset G. Rapid-onset causes HLBP and cerebral perfusion to be diminished quickly, taxing the brin's oxygen reserve. The subject is then at nsk for G-LOC [18].

23 1 \ G-LOC (a) G-time Tolerance Cuwe Human tolerance to +Gz (b) ElIcrt of G-onset on G Tokrance Muman tolerance to various G-onset rates adapted from [la] to + Gz transitions The effects of acceleration becorne more complicated when a -Gz maneuver is performed before a +Gz maneuver. When a pilot experiences a pend of -Gz directly preceding ffiz, G-tolerance is diminished [19]. This demase in +Gz tolerance caused by negative to positive Gz transitions has ken lrbeled the "push-puli" effect (PPE)[2]. Since a reduced G-tolerance increûses a pilot's risk of visual disturbance andor Ci- LOC at a lower ffiz threshold, the PPE remains a hazard for aircrew dunng flight. This problem has been expecienced by military tactical pilots [3-51 and avilian aembatic aviators [15, 201 for many years. However, for nasons stated in section 1.0. very little is knom about the complex cardiovascular reflexes occuning during the PPEM due to

24 expnmental limitations and even less is known about the effect of current G-protection countermeasures against the PPE. Countemieasures such as the anti-g suit, positive pressure breathing (PPB), and the anti-g stnining maneuver (AGSM) must be tested dunng PPEM simulations to discover their usefulness in counteracting the PPE. ültimately, a protection schedule must dso be developed to better defend pilots against the effects of negative-to-positive G-transitions. 2.6 TM table test for the push-pull effect As stated previously, the tilt table has recently ken used to study push-pull physiology [2 11. B y subjecting a person to a HUT-HDT-HUT sequence, the tilt table can reproduce the +Gz to -Gz to +Gz transition of the PPEM. This allows for the examination of the physiological response to the PPEM, the push-pull effect (PPE) Advantap of the tilt tabh simulation of the PPEM The tilt table is a good lab-based approach for push-pull testing which has several advmtages over other experimental methods. Tilting a subject at various angles for certain durations cm rnirnic maneuven experienced during tactical flight with the added advantage OF greater control over the testing environment. Although the amount -Gz and +Gz experienced by the subject are not of the same magnitude as in-flight or centrifuge situations, the tilt table can produce sirnilar patterns of physiological change. Monitoring

25 equipment that cm not be used in in-flight studies due to size and feasibility constraints can be readily utilized in the tilt table Iab [21]. With the tilt table, investigatocs also have instant access to the measurement apparatus. Equipment problems that would nonnally force an in-flight experiment to be aborted can be quickly addressed and corrected. Environmental concems such as dangerous winds, high temperatures. or bad weather that could compromise in-flight studies rue easily controlled for or of no concern in the tilt table lab Disadvantagcs of the tilt table simuiation of the PPEM The tilt table is limited as a labontory tool since it can not precisely mimic the inflight experience. Subjects cm only by exposed to a maximum of Gz (135' HDT, referenced from vertical) and +1 Gz (15O HUT, referenced from vertical) on the tilt table, far less than the -4 Gz to over +9 Gz experienced by tacticd aircrew when perfoming inflight maneuvers. The tilt table ha the further problem of not king similar to the cockpit of a iacticai aircraft. Different seating position, and the Iack of a control panel. control stick and foot pedals could al1 effect the experience of the subject and alter results.

26 2.7 Current countermeasures There is a point at which the cardiovascular mechanisms for coping with G begin to fail. As explained in section 2.2.2, as the magnitude of +Gz increases, the result is a gradua1 loss of vision followed by G-LOC. To avoid these problems and their associated risks, countermeasures have been developed in an attempt to increase Ci-tolerance. The oldest yet still most common protection method is the anti-g suit. Anti-G suits have been used since World War ii to counteract the effects of high +Gz accelerations [16]. These suits, wom around the legs and abdomen. contain air bladders which are inflated when gravito-inertid forces are above +2 Gz. This inflation causes pressure to be placed directly upon the lower extremities and splanchnic region. This results in increased periphenl vascular nsistance through increased lower body tissue pressure. a decrease in the venous pooling capacity of the lower limbs, increased venous retum, and elevation of the heart. All of these factors act to maintain HLBP under high +Gz and afford the wearer of the G-suit a Gz increase in G-tolerance Since its inception over 50 years ago, the G-suit has undergone few alterations, most of which have had only minor effects on G-protection. Since modem tactical aircraft are capable of achieving greater than +9 Gz, improved G-suits and grater G protection for pilots has become a necessity. Recent military aviation accidents have highlighted this shortcorning in G-protection. To combat this problem, acceleration physiologists began to develop new methods of G-protection including improved G-suits and new G-valves with innovative inflation schedules.

27 2.7.1 Extendcd Covecage G-suits Military establishments including the Royd Air Force (RAF), the United States Air Force the United States Navy (USN), and the Canadian Air Force (CAF) have made attempts to irnprove their G-protection with the development of a new genention of G-suits; respectively the FAGT, ATAGS, EAGLE, and STING. These G- suits follow the concept of extended bladder coverage over the lower extremities for increased G-protection. The extended coverage provided by these suits work on the principle that increased bladder coverage will cause a larger increase in lower body tissue pressure venus older style, cut-away G-suits. It is believed that this will allow for better maintenance of HLBP under high +Gz and. therefore, increased G-tolerance. Studies have ken inconclusive on whether these extended coverage G-sui ts actually increase maximum G-tolerance. However, extended coverage G-suits have been shown to reduce pilot fatigue and increase G-tolennce time venus older style G-sui& [23.24]. Also. ment centrifuge and in-flight tests of STING have provided definitive evidence that extended coverage G-suits offer a significant increase in protection over standard G-sui ts w hen used with PPB as part of a G-protection ensemble ( The control of Csuit hflation by the Evalve: timing and rate of inflation The anti-g suit inflates when a pilot is exposed to increased gravito-inertial forces. This inflation is conmlled by a volve which is sensitive to G-intensity. When a

28 pilot experiences increased +Gz the valve opens and. using air bled from the jet engine. the G-sui t is inflated. Current, standard O-valves are mec hanical and their design is viriuall y unc hanged from those used since the 1940s. When gravito-inertial forces are above +2 Gz, the valve passively opens causing the G-suit to inflate at a rate of approximately 1.5 psi per G to a maximum of 10 psi [Ml. This +Z Gz dehy is necessaiy to prevent the G-suit from inflating under circumstances in which it is not meded such as aircnft buffeting and low G-level moderate tums. In these situations, G-suit inflation cm be uncornfortable and distracting to the pilot There has been considerable debate in the field of aviation over when and how npidly the G-suit should inflate. It seems logicai that, since HLBP begins to decrease irnmediately with the onset of Gz and that the G-suit provides hypertension upon inflation to countenct this decrease, the G-valve should provide pressures which coincide with the G-profile. However, studies on this subject have been inconclusive. Scientific conclusions on optimal G-suit inflation rates have nnged from immediate, very rapid G-suit inflation as a necessity for increased O-tolerance to those studies that show slower-onset inflation or even a slight delay in the onset of inflation has no il1 effect on G-protection [30]. The overriding problem is the Iack of direct evidence to support any conclusion.

29 27.3 Use of the anti-g suit for protection against the push-pull effoet Since few studies have been conducted on G-protection during the PPEM, very little is known about the protection afforded by the anti-g suit against the PPE. In-flight push-pull protection studies have found that although the initial decrease in blood pressure caused by negative-to-positive G-transition was unaided by G-suit inflation, the G-suit did speed the rate of blwd pressure recovery compared to unprotected mns [l, 311. Thus. the G-suit appears to pmvide some protection against the PPE. However. the optimal tirne for G-suit inflation dunng the PPEM for maximum protection benefits has yet to be examined The development of an electronic <smart9 G-valve for protection against the push-pull effet Once a G-suit inflation timing and pressure schedule is discovered to optimally pmtect pilots against the PPE, there will be a need to develop a system thai will be able to deliver this schedule accordingly. Efforts have been made to develop an electronic G- valve which can read recent G-profile-history during flight. This 'smart' valve could, in real-time, interpret the G-profile, recognize if a PPEM has acurred determine what pressure schedule is necessary then deliver it accordingly.

30 2,s Problem The physiological effects of ffiz the countenneasures developed to counteract these effects. and the protection afforded by this equipment has been studied thomughly since World War ïi [22]. However, very linle of this research has been focused on the push-pull effect. As stated previously, knowledge of the PPE is incomplete since complex measurements are difficult to perform using current appmtus and protocols. Because of these limitations, not only is very little known about the physiologic effects of the PPEM, even less is known about how to protect tactical pilots from its effect. Investigation is therefore warranted. 23 Purpose of this study The purpose of this study is to use the low-intensity tilt table mode1 of the PPEM while intervening with various G-suit schedules to determine which schedule is the most effective against the PPE. It is hoped that this will: (1) Provide insight into the cardiovascular response to the PPEM. (2) ïmprove the understanding of the effect of various G-suit inflation timing and pressure schedules on protection against the PPEM.

31 (3) Aïd in the discovery of a protection system with an electronic 'smart' G-valve that could deliver this G-suit timing and pressure schedule for optimal protection against the PPEM. (1) G-suit inflation will have no effect on the blood pressure response to the PPEM. (2) Varying the timing of G-suit inflation will have no effect on the blood pressure nsponse to the PPEM. (3) Varying the pressure of G-suit inflation will have no effect on the blood pressure response to the PPEM Expectations Based on the known Rsponse to the HUT-HDT-HUT tilt table simulation of the PPEM [8] and the hemodynamic effects of G-suit inflation [22,32] certain results are expected. It is known that G-suit inflation during HUT causes increased vascular resistance in the lower extremities and, therefore, demased translocation of central blood volume toward the lower vasculature. Thus, it is expected that G-suit inflation during transition to and upon reacbing subsequent HUT will act to help maintain HLBP and, therefore, ameliorate the PPE. Increased inflation pressure is expected to further aid in the maintenance of HLBP upon reaching subsequent HUT and therefore, offer even greater assistance in arneliorating the PPE.

32 2.12 G-suit infiation schedules Various G-suit inflation schedules will be used to detemiine if these expectations are indeed correct. G-suit schedules were selected which varied by initial time of inflation (inflation dunng transition to subsequent HUT venus inflation upon reac hing subsequent HUT), inflation onset me (normal versus slow), and maximum inflation pressure (normal versus high). The profiles of these schedules are illustrated in Figure 2-5 and explained in Table 2-1 (see next page) Significance of this Expriment As stated previously, recent studies have shown that the PPE has been a contnbuting factor in numerous military aircraft accidents [3-51. These studies have concluded that an impaireci G-tolerance caused by the PPEM is a major nsk to pilot performance and could possibly cause injury andor death. Thus, it is important to lem more about the PPEM and discover methods to protect pilots against its effect. This research wi II provide insight into the neurological and cardiovascular processes involved in the PPE. It will also lead to a pater understanding of the protection schedules necessary to counteract the effects -Gz to +Gz transitions. Hopefully, this information will contribute to the creation of a new electmnic G-valve algorithm and, therefore. improved G-suit inflation schedules that will better protect pilots during al1 aspects of high performance flight. Ultimately, this will Save aircrew from potentiaî injury andior loss of life.

33 Figure 2-5 Tilt table profile with experimentai schedules 135O HDT nit Angk 15 O Hm 2 psi \ "npmtcmed (no inflation) Table 2-1 Explmation of G-suit inilation schedules Run Unpmtected RDTr PsüTr Description of G-suit scbeduie No G-suit inflation Pressure aormzil, inflaiion During Triinsition to Hm- Pressure nod, slow inflation During T ~ u oto n HUE I

34 3.0 Review of Literature 3.1 The physiological effeet of expusure to G As stated in section 2.2. most healthy individuais can cope with the effects of +L Gz without difficulty. However, problems arise in situations such as military tactical aviation w here pilots experience gravi to-inertial forces beyond + 1 Gz. Increased +Gz causes a dative increase in the hydrostatic forces within dl vessels in the circulatory system. This often results in inadequüte blood pressure above hem level and decreased perfusion of the brain. This decreased perfusion leads to visual disturbances and the possibility of gravity induced loss of consciousness (G-LOC)[ Hydmstatic effkcts Blomqvist and Stone presented a thomugh, mathematical explanation of the hydrostatic changes caused by +GE [13]. They simplify hydrostatic forces under high +Gz conditions by assurning b l d in the vasculature is analogous to a column of tluid in a ngid container. This assumption allows physicd pnnciples that govem a fluid-filied column to be applied to the cardiovascular system.

35 The hydrostatic pressure at the bottom of a column of fluid in a rigid container is a product of the density of the fluid. the applied gravito-inertiai force. and the height of the column. Equation 3-1 Where P is the pressure, p is equal to the density of the fluid, G is the gravito-inertial force. and h is the height of the column. If the density of the blood in an individual is assumed to be constant and. as assumed by Blomqvist and Stone. the blood in an individual in an upright position is an unalterrd rigid column. Equation 3-2 can be used to estimate changes in blood pressure caused by gravito-inenial forces. Equation 3-2 Where Pm is the calculated systolic blood pressure (SBP) at a certain distance and, P is the reference point SBP (heart-level SBP, in most cases). For instance, to calculate the effect of +1 Gz on b l d pressure at head level, the values for density of blood (1/13.1), gravito-inenial force (+1 Gz = 9.8 md), and the

36 column height (for example, heart-to-eye distance = 30 cm) can be substituted into Equation 3-2: As illustrated in Figure 3-1, Equation 3-2 cm be used to determine systolic blood pressure ai any distance from the hem. in the footward or headward direction. Figure 3-1 Schemtic of systolic bkà prrswur in the supine and emt position at +1 Ga adapted h m 1181

37 The density of blood and the height of the column will remain nearly constant under most acceleration forces. Thus, according to Equation 3-2, changes in the gravitoinertial force itself is thc only variable that altea hydrostatic column pressure. For instance, if the blood pressure at hem level is 120 mmhg, at +3 Gz the blwd pressure at head level will be: P, =P,+pGh =120 mmhg + (11 l3.l)(9.8 x 3)(-30) = =54 mmhg Thus. head-level blood pressure (HLBP) under increased accelention can be calculated using Equation 3-2, decreasing at approximately 22 mmhg per unit of Gz. In a system comprised of ngid tubes of unvarying diameter, blood flow would not be impeded by these differences in pressure. However, the humon cardiovascular system is not a set of tigid tubes as assumed in the equations above. The cardiovascular system consists of multi-branched, elastic vasculature of varying dimeter containing blood of unique composition and propenies. Nonetheless, physical pnnciples cm still be applied to this varying system. One of the principles, Poiseuille's Law, relates the fiow of fiuid in a cylinàrical tube as directly proportional to the pressure difference across the tube, directly proportional to the fourth power of the radius of the tube, inversely proportional the

38 length of the tube. and inversely proportional the viscosity of the fluid These relationships are illustrated in Equation 3-3: Equation 3-3 Where Q is the blood flow. (P,- P,,) is the pressure difference, r is the radius of the tube, q is the viscosity of the fluid (blood), C is the length of the tube, and R/8 is the proportionali ty constant [33]. Since resistance (R) is pressure divided by flow, Equation 3-3 cm be rearranged to give the resistance to flow. Equation 3-4 Resistance is, therefore, proportional to the viscosity of the fluid and the dimensions of the tube. In the cardiovascular system, the length of the circulation and the viscosity of blood is nearly constant. Therefore. changes in resistance to flow are main1 y due to

39 changes in the radius of the vessels. Since the radius is to the fourth power and is inversely proportional to R. smdl changes in radius can cause a tremendous change in resistance and flow. These changes in radius can be initiated by many environmentai factors inc luding gravito-inertial forces. Gnvito-inertial forces act not only on the body but the blood in the vessels as weli. ffiz causes biood to be shifted in the footward direction- Due to the elastic nature of the venous circulation, this shift results in passive dilation of the lower vasculature and a pooling of blood in the lower limbs. This increase in blood volume in the lower extremities creates a problem. Since blood is pooled in the legs, there is less blood in the vasculature above heart level. This results in the decteased diameter of vessels above hem level and, therefore, decreased blood flow above the hem- Gravito-inertial forces also make maintenance of blood flow more difficult. Under increased gravito-inertial force, the heart must perfom, more forceful contractions in order to overcome increased hydrostatic effects and maintain bld flow above hemlevel. Therefore, it is more difficult for the heart to maintain blood flow to the head. Ultimately, increased gravito-inertial forces result in decreased bld flow and decreased blood pressure above hem-level. This results in a reduction in head-ievel blood pressure (HLBP) which leads to decreased perfusion of the eyes and brain. This lack of perfusion is a significant problem caused by inmased magnitudes of +Gz.

40 3J.2 Importance of HLBP changes Changes in HLBP caused by +Gz are of great interest and importance. Decreased HLBP effects the eyes and the brain, two vital organs dunng flight. Any loss of vision or decrease in cognitive ability could drastically effect pilot cornpetence and put aircrew at risk for injury andor death. Therefore. in an effort to diminish this risk. numerous studies have been performed to learn more about the effects of +Gz and its effect on HLBP. One of the pioneen of G-research was Earl Wood. Before Wood conducted his studies on the effect of accelention on humans in the L94ûs, it had long been believed that the visual disturbances and unconsciousness associated with increased +Gz was due to a decrease in venous retum (VR). However, Wood found that these disturbances were a result of a decrease in HLBP, not a decreased VR [34]. Wood subjected healthy adult volunteers to npid-onset +Gz of various magnitudes using the human centrifuge at the Mayo research facility He discovered that as gravito-inertial forces increased above +4 Gz. blood flow to the head was compromised. This lack of perfusion resulted in a loss of peripheral vision (greyout), followed by complete loss of vision (blackout), and ul ti matel y resulted in gravi ty induced loss of consciousness (G-LOC). Wood concluded that the loss of vision and loss of consciousness caused by high +Gz was a result of the inability of the body's reflex mechanisms to cope with these increased hydrostatic forces and maintain HLBP 1161.

41 3.1.3 Reflex mechanism for HLBP maintenance The carotid baroreceptors, along with the cardio-pulmonary baroreceptors of the aoitic arch and other less understood sensoa throughout the cardiovaxular system, are part of n neurological mechanism which controls HLBP transient fluctuations. Located in the camtid sinus, the carotid baroreceptors are specialized stretch receptots which rapidly estimate changes in blood pressure in the head by sensing changes in the diameter of the camtid orteries. The carotid baroreceptors attempt to maintain appropriate HLBP by sending an afferent signal to the cardiovûscular control centre of the medulla whenever the diameter of the carotids change. If the afferent message from the carotid baroreceptors indicates that there is an inmase in the dimeter of the carotid arteries. the medulla interprets this as an increase in HLBP. The medulla sen& an efferent message to the end organs by stimulating the vagus nerve and decreasing sympathetic nervous system activity. This results in a reflex decrease in HR. a decreased stroke volume (SV) and. through periphed vasodilation. a decreased total peripheral resistance ("PR). This reflex acts to maintain HLBP and keep the brain perfused under varying hydrostatic forces. If the carotid buoreceptors sense decreased stretch in the carotid meries an opposite reflex reaction occurs. The medulla recognizes decreased carotid stretch as a decrease in HLBP and sends an efferent message inhibiting the vagus nerve, thus increasing HR. The message also stimulates sympathetic nervous system activity cesulting in an increased SV and increased TPR. This translates into an elevation of heart level BP in an attempt to maintain HLBP.

42 The cardiovascular reflexes are invoked when carotid arterial stretch is increased or decreased occur during -Gz and +Gz. This is illustrated in Figure The push-pull effect Another dimension of complexity is added to the cardiovascular effects of aviation when a pilot performs a -Gz maneuver before a +Gz maneuver. Although tactical pilots do not routinely experience sustained -Gz, they sometimes push' -Gz after a +Gz tum in order to gain enough aerodynamic energy to 'pull' into another +Gz tum. This is olten referred to as 'unloading' the aircnft since it is used to increase acceleration in the subsequent ffiz tum. Pilots also experience -Gz acceleration dunng air combat when navigating their plane into a nose down position white attempting to get a better view of a target. In these situations. pilots sometimes 'push' -Gz before they 'pull' +Gz [Il. This maneuver is illustrated in Figure 3-2. Figure 3-2 adapted fmm [35]

43 It has been found that when a pilot experiences G z directly before +Gz. G- tolerance is diminished [19]. This nduction in G-tolemnce can be attributed to cardiovascular reflexes. When exposed to -Gz. the body's reflexes react by decreasing HR, cardiac contractility, and TPR in order to defend agsiinst high HLBP. Yet, under 42. HR. cvdiac contnctility, and TPR must be incieased in order to maintain iidequate perfusion of the brain and avoid G-LOC. Therefore, by expenencing -Gz directly before a +Gz maneuver, the body is ill-prepared to cope with +Gz [36]. The resulting decreased G-tolerance phenornenon has ken termed the "push-pull effect" (21. Since a reduced +Gz tolerance increases the nsk of pilot visuai disturbance andior G-LOC nt a lower ffiz threshold the push-pull effect remains a hazard for ircrew during flight. This hazard is believed to have resulted in several aircraft accidents. Brush examined the prevalence of the push-pull effect in recent Canadian Forces (CF) accidents and incidents [3]. He reviewed 284 CF jet and miner accidents that occurred from of these accidents were selected for ""detailed review". Of these accidents, the push-pull effect was a probable or possible factor in iit lest 5 accidents and 2 incidents. Due to the "hazards and insidious nature" of the push-pull effect. Bmsh stressed the need for continued push-pull research and inc~ased aircrew education of i ts potential hazards. A similar study was conducted by Michaud and Lyons for United States Air Force (USAF) [SI. They reviewed USAF reports of the 24 accidents from detennined to be caused by G-LOC. They focused on the maneuvers prior to the accidents such as extension. diving, acceleration, and unloading that could cause the

44 push-pull effect. They concluded that in 7 of the 24 accidents (298) the push-pull effect was either probable or highly probable. Michaud and Lyons therefore concluded that push-pull is an operatïonally significant source of risk for accidents in USAF high- performance aircnft. They suggest inmased pilot education and aitered protection training as a means of increasing awareness of the push-pull effect in the USAF and the flying community. Michaud and Lyons also examined the frequency of the push-pull effect in the USAF by reviewing 48 head-up display videotapes containing over 240 USAF air combat training missions [4]. For each mission they noted the presence of push-pull effect maneuvers (PPEMs). PPEMs were determined by Gz profiles of a pend of less than 4.8 Gz lasting for moe than 1 second followed by a pend of pater than +3 Gz king for more than 4 seconds. Using this criteria, the authors found that almost one-third of the engagements they reviewed contained PPEMs. They therefore concluded that push-pull effect is present in USAF fighter missions and considered it a significant source of risk for aircraft accidents. Even though the problem of the push-pull effect has been experienced and documented by military tactical pilots [3-51 and civilian aerobatic aviators [15,20] for many years, very little physiology of this effect is hown apart from basic BP and HR measurements, As stated previously. physiological measuns during the push-pull maneuver are difficult to collect since most centrifuges, a common investigative tool in acceleration research. are incapable of ~producing -GE to +Gz acceierations. In-flight experiments are dso difficult to perform because the constraints of the cockpit environment limit the type

45 and amount of data that can be collected. In-flight experiments are also lirnited by the pilots ability to follow flight paths with the precision and repetition neeâed for proper scientific research. Despite these limitations. there is still a smail base of literature on push-pull. The rwts of push-pull research have been traced to an in-fiight study performed by Von Beckh in the late 1950's Von Beckh hiid pilots in jet propelled intercepior aircraft follow various flight paths in an attempt to study human reactions to acceleration. One of the flight paths. "post-weightlessness acceleration" consisted of a penod of b'weightlessness" (less than O Gz) followed by a d.5-6 Gz spiral. When examining the results of this experiment, Von Beckh noted that in these pst-weightlessness trials, pilots' G-tolerance was greatly diminished when compaxed to other flight paths performed in the study. Although Von Beckh did not give a through explanation for these findings, his nseûrch can be regarded as a prelude to the push-pull experiments of the future, Studies of civilian aerobatic pi lots also foreshadowed modem push-pull research. Mohler examined the effects of G on pilots by studying the gravito-inertial forces experienced during aerobatics [15]. He studied various aerobatic maneuvers including "loops", "rolls", and "pull-outs". Mohler noted that during one maneuver termed the "vertical 8, where the aerobatic pilot would experience -Gz before ffiz, there was a delay in the cardiovascular refiex response to +Gz. Even though Mohler stated that no physiological h m would come from this igz transition, he mentioned that the -Gz to +Gz maneuver did increase the Iikelihood of blackout.

46 Bloodwell also studied civilian aerobatic competitive flying [20]. He measured HR, G exposure, and maneuvenng time for 15 pilots involved in aerobatic cornpetitions in Fredncksburg. Virginia and Fond du Lac, Wisconsin in L98 1. Bloodwell observed that the mean minimal HR occurred during -Gz exposures and the mean maximal HR occurred during +Gz exposures. He also noted that the maneuver most difficult for efficient cardiovascular compensation involved cyclic variations of negative and positive G. Although it was not yet labeled as such, this +G transition mimicked what would later be termed the push-pull maneuver. In 1990, Diednchs studied the effects of negative to positive G transitions by examining flight profile statistics compiled from USAF training missions [37]. Using data collected by the US AF Sdety and Inspection Center of California, Diednchs found that the highest incidence of G-LOC occurred when a pilot perfonmd a "sp1it-s" followed by either r "spin prevent or spin recovery and loop". Diednchs noted that this sequence of maneuvers subjected the pilot to negative or zero G just prior to high +Gz. He believed that the disproportionate amount of G-LOC episodes accompanying this maneuver sequence were caused by this G-transition. Diednchs hypothesized that r pend of -Gz immediately pnor to a +Gz maneuver resulted in a demased O-tolerance and therefore G-LOC at a lower G-level. The author stated that this hypothesis had been supported by the testimonials of over 3 0 trainer and fighter pilots who were questioned in a non-threatening environment during physiological training at Williams Air Force Base. Texas. He concluded that there was a need for increased military research and pilot education with respect to the adverse effccts of -Gz to +Gz transitions.

47 Lehr, Prior, and colleagues were the fint to study the effects of -Gz exposure on G-tolerance [19]. Using a multi-axled. gimballing human centrifuge, Lehr and Prior exposed subjects to either - 1.O, -1.4, or -1.8 Gz for 2, 16, or 30 seconds. Subjects were then immediately exposed to ffiz increasing at 1 G per second until they reached their reiaxed G-tolerance (determined as 60% loss of periphenl vision). The results showed a significant reduciion in relaxed G-toierance when -Gz occurred pnor to +Gz. The influence of the magnitude of -Gz was found to be relatively small, however. longer durations of -Gz exposure were found to cause a greater reduction in G-tolerance. Lehr and Prior found th* even -Gz exposures of only 2 seconds were enough to cause a significant reduction in nomal G-tolerance. In an in-flight study by Banks and Gray examined the effect of -Gz exposure on HR [38]. 2 Canadian Forces pilots were studied while passengers in CF4 14 Tutor jet aircrafts. The flight profile included a 15 second, - 1 Gz maneuver which was preceded and followed by 5 minutes of straight, level flight at +1 Gz. HR was monitored and ncorded using and ECG. Both pilois were observed to have irnmediate and profound bradycardia dunng -Gz exposure. The investigators attributed this decrease in HR to increased ponsympathetic activi ty as a result of carotid barorecepior stimulation. Banks and Gray noted that in addition to bradycardia, this increased parasympathetic activity would also cause periphetal vasodilation and decreased cardiac contractility. They believed that the parasympathetic activity during Gz could adversely affect Ci-tolerance since the bady requires increased caniiac output and vasoconstriction during +Gz stress. Banks and Gray concluded that future operational research should focus on the potential hazards and implications of -Gz exposure on G-tolemce.

48 Banks continued this research using the Coriolis Acceleration Platform (CAP)[2]. The CAP is a circular, horimntally rotating platfom with a movable cab on a track along its radius. Banks placed his subjects in a supine, seated position in this moveable cab. By spinning the plaâorm at certain speeds and moving the subject along the track. Banks could alter the magnitude of -Gz and ffiz experienced by the subject by changing the distance of the subject's head or feet fmm the edge of the platform [2]. Banks found that exposing subjects to -Gz More +Gz resulted in decreased BP and decreased G- tolerance in the subsequent +Gz exposure. Since this negative to positive Gz exposure rnimics the anaiogous to a pilot 'push9-ing forward then 'pull'-ing back on an aircnfts yoke. Banks labeled the decreased G-tolerance caused by IGz transition the "push-pull effect". In his studies with the CAP. Banks also examined the effect of magnitude and duration at -Gz on G-tolerûnce during a subsequent +Gz. By altering these variables. Banks determined that both magnitude and duration of the -Gz exposure immediately preceding ffiz acted to decrease G-tolemce. The greater the magnitude and the longer duration at -Gz, the greater the âecrease in G-tolerance [2,39]. G-transitions can cause large changes in cvotid arterial pressure and, therefore, carotid baroreceptor activity. Understanding that this could possibly effect the control of vascular sist tance and ultimately G-tolerance, Dœ et al. examined the effect of changes in cmtid sinus pressure on the magnitude and time course of bmreceptor mediated vascular nsponses [40]. Using anesthetized dogs, Doe constnicted a perfusion circuit which allowed independent perhision pressure and flow control of the aorta and the carotid sinuses (which. as stated in section 3.13, are the two main baroreceptor areas). By

49 keeping subdiaphramatic perfusion pressure constant and altering carotid perfusion pressure. Doe was able to determine the effect of alte~d carotid bmreceptor pressure on vascular resistance. Doe found that the time tdcen to reach 75% of the maximum dilator response was significantly shorter than that for the corresponding constrictor response. Doe concluded that, since carotid baroreceptor mediated vasodilation occurs more npidly than vasoconstriction, maneuvers such as -Gz accelemtions that cause mpid changes in carotid baroreceptor pressures may reduce vascular resistance. Thus. when -Gz precedes +Gz. Doe predicted larger demases in artenal BP and a decreased G-tolennce dunng the subsequent +Gz exposure. In 1999, Wright and Buick published an in-flight study of the push-pull effect in an attempt to validate the centrifuge as a ground-based simulator of the push-pull maneuver [4 11. Using CF4 8 aircraft, Wright and Buick exposed 16 relaxed and unpmtected subjects to 2 G/sec onset rate, 15 second duration G-profiles, in increments of 0.5 G over the subject's G-tolerance. These different Gtxposures were preceded by 5 seconds of +1.4 to -2 Gz. Head and heart-level BP were measured as well as ear opacity. The investigators found that the push-pull scenarios (-Gz to +Gz transitions) caused a significant reduction in G-tolerance. G-tolerance was decreased by up to 1.3 Gz when ffiz was preceded by -0.5 to -2.0 Gz. This reduction was found to be similar to previously reported centrifuge data, therefore validating the multi-axled, gimballing centrifuge as a useful twl in push-pull nsearch.

50 3.3 Tilt table test for the push-pull effect The experimental tool used most recently to study the push-pull effect is the tilt table. As stated in section 1.4, the tilt table is a rotating bed that cm be tilted amund its centre point. A subject can be secured to the table in a supine or seated position and can be tilted at various angles to observe physiologicd changes. A rapid HUT to HDT to HUT sequence cm be used to mimic the push-pull effect maneuver Review of tilt table acceleration research The tilt table has ken used in acceleration research for many years but has also been successfully implemented in many other cardiovascular investigative applications including syncope research [ Since this is an acceleration study, the focus of this review will be upon reports involving tilt table expenments for G research. In 1941, Graybiel and McFarland investigated the use of n tilt table for aviation medicine Using a custom made tilt table, they subjected 91 healthy individuals (the majonty of which were pilots) to HUT 65" hm horizontal in order to place gravitational stress on the subjects' cardiovascular system. Subjects were left in this position for up to 30 minutes unless collapse occurred During the experiment pulse rate and bld pressure measurements were made at 1 to 3 minute intervals. AIthough 69 of the subjects tolerated HUT quite well. 9 of the 9 L subjects collapsed and 13 subjects responded prly to HUT. The investigators noted that collapse usually occuned within the frst few minutes of the

51 test after a rapid increase in pulse rate, a decrease in pulse pressure. and a large decrease in sy stolic BP. The subject was often observed to penpire and develop pallor of the face and hands just pnor to fainting. Graybiel and McFarland concluded chat this tilt table test was a good test of physical fimess and believed that it could be used as a physiological aptitude test for aviators' G-iolerançe. However, this daim was Iater contradicted by Estes who found only weak correlations between tilt table response and G-tolerance [43]. Green and his colleagues studied the effect of tilt on BP and HR [44]. Of the over 200 subjects tested, 15 were detailed in Green's report. Subjects were tilted ai a moderate rate of speed from the 20" HUT position to the 4S0 HDT position wheni they remained for at least 15 seconds. Subjects were then retumed to 20' HUT. Thmughout the experiment, BP was recorded from either the radial or brachial artery and HR was recorded using an ECG. Green found that during HDT, BP increased for a period of 8 to 18 seconds then pmceeded to fa11 towards initial levels. HR was found to slow abruptly upon the inmase of BP in the majority of subjects. Upon retm to HüT, BP was found to decrease for 8 to 18 seconds then begin to recover towards normal. HR was found to increase suddenly upon the decrease of BP. Green postulated that the relation between body position. BP, and KR suggested that the change in HR was one of the reflex mechanisms that was responsible for the regulation of BP. In 1950, Wilkins et al. studied the cardiovascuiar effects of -Ch using a tilt table [7]. Wilkins subjected 42 individuals to 7S0 HDT hm horizontal (considered a 1 Gz shift) and 75" HOT from 75" HUT (considered a 2 Gz shift). The HDT phase was

52 maintained for between 2-30 minutes depending on the necessary measurements and subject tolerance. Artenal BP. venous pressure. and subjective comments were recorded. Most subjects experiencing HDT complained of a wm, flushed and congested face. Subjects also noted cranial swelling, breathing difficulties. and watering eyes. Objectively, HDT was found to cause numerous cordiovascular effects. Wilkins found the head-down position caused a siowing of the HR which was often accompanied by kat imgularities. Stroke volume and CO was found to increase during HDT. Arterial BP decreased slightly upon HDT and then decreased even further after a 3 or 4 pulse beats. Wilkins noted that when a subject was tilted head-down from the HUT position that the acute changes in arterial BP and HFt were "qualitatively sirnilar to but quantitatively greater than" when an individual is subjected to HDT from horizontal. Wilkins believed that this phenomenon could be attributed to the "opposite effects" of experiencing HUT before HDT, Wilkins findings were supported by Ryan and his colleagues [6]. Ryan's protocol involved subjects experiencing a sequence of horizontal to 60" HDT followed by three successive 60" HUT to 60 HDT tilts then a period of rest at horizontal. ECG and subject perceptions were recorded. Dunng HDT, subjects had complainu similar to Wilkins' group. These included increased pressure in the head. headache, fullness of the face, eyebulging, and respiratory difficulties. Ryan observed that HR decreased when subjects were tilted from the horizontal to HDT position. This decrease was more pronounced for the HUT to HDT tilts. Ryan calculated that 93% of this HR change occmd in the first 3 seconds after naching HDT.

53 HR decreased for 15 seconds after HDT was reached then slowly recovered towards resting values. The possibility of arrythmias was also noted. Ryan found the opposite results For HDT io HUT transitions. When a subject went from HDT to HUT. HR increased and 928 of this change occurred within the first 3 seconds of HUT. After 15 seconds, HR began to retum towards resting levels. Ryan believed that the 15 second delay before retum iowards resting values w u due to the carotid sinus reflex mechanism. In 1960, Fletcher and Girling also used a tilt table to investigate the effect of tilt angle on HR [45]. Their experiment involved subjects in tilt positions in multiples 45' to the horizontal, rnaintained for 30 seconds each. HR was recorded using chest electrodes and a cardiotachometer. A systemûtic relationship was found between HR and tilt angle for al1 subjects. HR was highest in the vertical HUT position and lowest in the vertical HDT position. The difference in HR between vertical HUT and vertical HDT was quite large ranging from bpm with an average difference of 40 bpm. Fietcher and Girling also noted that cardiac deceleration was a faster pmcess thm cardiac rceleration. Deceleration took 2-3 seconds whereas acceleration needed up to 20 seconds for completion. It was suggested that this difference was due to the different mechanisms involved in cardio-acceleration and deceleration. In 1%3, refemng to the importance of body position to systemic BP and cerebrai blood flow during gravity-induced flight. Abel examined baroreceptor influence on postural changes in BP and carotid blood flow [46]. Abel monitored the HR. mean systemic pressure, and carotid bld flow of sixteen anesthetized dogs positioned for 10 minutes at horizontal, 30" HDT, and 30" HUT. The dogs were then partially or totally

54 denervated to block the effect of the baroreceptor reflex arc and the measurements were repeated. Abel found that the animals' ability to compensate to HDT and HUT were greatly impaired by denervation. During the HUT denervation nins, HR remained nearly unaltered while both BP and carotid blood flow dropped precipitously with little compensation. During the denervated HDT mns, HR remained unchanged while both BP and blood flow increased slightly. These findings suggest the importance of baroreceptor nflexes as part of the body's compensating mechanisms for gravity transitions. In Tuckman and Shillingford investigated the effect of different degrees of tilt on cardiac output (CO), HR and BP [47]. A tilt table was used to tilt 33 subjects From a horizontai, supine position to either LOO, 20'. 30, '. or 60' HUT position for 20 minutes. Subjects were then retumed to horizontai. HR. systolic blood pressure (SBP). and diabolic blood were recorded throughout the expriment. Mean artenal blood pressure (MAP) and pulse pressure (PP) were calculated from SBP and DBP values. Stroke volume (SV) and CO was measured using a dye indicator injection. TPR was then calculated using MAP and CO measurements. Tuckrnan found HR remained relatively unchanged at 10' md 20" HUT and increased significantly at tilt angles 2 30' W. SBP. MAP, and PP were found to not alter significantly at any of the tilt position. DBP increased at dl angles of tilt, however. these changes were not significant until tilt mgle was 2 30'. SV and CO were found to decrease gradually but significantly for each successive angle of HüT. TPR increased significantiy at ail angles of HUT. Upon ntum to horizontal. a delay of at least minutes occurred before CO was observed at the level recorded before tilt.

55 In 1998, Newman et ai. used the tilt table to in an attempt to gather evidence of baroreflex adaptation to repetitive +Gz in fighter pilots [12]. Newman studied the cardiovascular responses of 8 pilots and 12 non-pilots to the rapid-onset tilts to the +7S0 HUT position. Each HUT was held for 2 minutes before return to supine. SBP, DBP. MAP. PP. and HR were recorded throughout the procedure for al1 subjects. Newman found that the cardiovascular response to HUT was fundmentaily different between the pilot and non-pilot groups. When exposed to HUT. pilots experienced a sigificant increase in systolic. diastolic. and mean artenal pressure. PP was virtually unchanged. In the non-pilot group. while the change in SBP, DBP and MAP was minimal w hile PP was found to decrease significantly. HR was found to increase significantly for both groups. Newman believed that this difference in cardiovascular response was evidence that the baromflex mechanisms of fighter pilots had adapted to ffiz as a result of fiequent G exposures Why the tilt-table G-rtsearch gap of over JO years? A very conspicuous gap in tilt table G-nsearch of over 30 years ( ) may have been noticed above. The lack of acceletation investigations using the tilt table can be expiained. Even though the jet aircraft was invented dunng World War II, most planes of that era were stiil powered by propellets and. therefore, had a lirnited G-envelope.

56 Consequently, human G-research only needed to probe within this envelope. Therefore. the tilt table, even with its low G-threshold, was a prominent tool in G-research. Over time. as jet aircraft became the military standard, the G-envelope became larger and more pilots experienced the negative effects of high-gz. G-LOC was recognized as a main contributor many tactical aviation incidents and acceleration physiologists realized thüt more high-gz reseiirch was necessary. However, due to its limited Genvelope. the tilt table could not simulate these high-gz conditions. Therefon. the investigative focus shifted to methods that could administer large magnitude accelentions, namely the centrifuge and in-flight research The tilt table as a method for examining the push-pull effect With the ment acknowledgment of the push-pull effect as a cause of numemus military aviation accidents [3-51 the tilt table has seen a resurgence in the field of G research. By subjecting a penon to a HUT to HDT to HUT sequence, the tilt table cm ceproduce the hypotensive response to the push-pull maneuver [21]. This technique has both advantages and disadvantages which were outlined in section Review of the tilt tabk simulation of the push-puu effkct maneuver Goodman and LeSage [21] recently used the tilt table to study the push-pull effect. 9 subjects were exposed to a senes HUT-HDT-HUT sequences that varied in HDT

57 angle (supine. 15O. or 45' HD) and HDT duration (7 or 15 seconds). MAP. HR, and impedance cardiography data was collected from each subject. These values were used to cdcdate SV and TPR. The investigaton found that the tilt table could reproduce cardiovascular responses seen with the push-pull effect maneuver. They reported that the HUT-EDT- HUT produced a decreased HR. inçreased SV, and decreased heiut-ievel MAP in the subsequent HUT maneuver for al1 tilt angles and durations. Tilting to the head-down position also caused a shift in blood to the torso as measured by a decrease in impedance (20). The HUT-HDT-HUT sequence resulted in incomplete recovery of HR. TPR and MAP which Goodman and LeSage concluded was caused by a delay in sympathetic drive. These results are sirnilar to the physiological responses to the push-pull maneuver previously observed in the centrifuge, in the aircraft. and on the CAP [l, 2, , Anti-G suit There is a point at which the cardiovascular mechanisms for coping with G begin to fail. As explaincd in section as the magnitude of +Gz inmases, the result is a gradua1 loss of vision followed by G-LOC. To avoid these problems and their associated risks, countenneasures such as the anti-g suit have been developed in an attempt to increase G-tolerance. AntiG suits (also known simply as G-suits) have been used since WorId War li to counteraft the effects of high +Gz accelerations [16]. These suits, wom around the legs

58 and abdomen, contain ait bladders which are inflated w hen gravito-inertial forces are above +2 Gz. This results in increased peripheral vascular resistance through increased lower body tissue pressure, a decrease in the venous pooling capacity of the lower limbs, increased venous retum, and elevation of the hem. Al1 of these factors act to maintain HLBP under high ffiz and afford the wearer of the G-suit a Gz increase in G- tolerance [22] The G-suit inflation during tilt Numerous studies have exarnined the effect of G-suit inflation while in-flight or in the centrifuge. However, very few stwlies have been conducted using both the tilt table and the G-suit. In a prelude to tilt/g-suit experiments, the effect of G-suit inflation in a 1 G environment was investigated by MacKenzie et al. in 1945 [48]. Interested in the effects of the G-suit on hem rate, the investigators recorded the hem rate of 11 seated subjects using a cardiotachometer from seconds before inflation to seconds after the release of pressure. Heart rate was found to slow for al1 11 subjects dunng G-suit inflation. Moreover, the investigators observed a similar pattern for al1 subjects upon inflation of the G-suit. The HR did not change for 34 seconds after inflation then HR decreased by 1025% for approximately 5 seconds. HR then attempted to recover towards pre-inflation values. HR recovered fuuy within 1 to 2 seconds after the nlease of pressure.

59 In 1969, Gray and colleagues studied the effect of G-suit inflation on cardiovascular dynamics [49]. For 5 of their 18 subjects. G-suit inflated with the subjects in the 60 HUT position. Hem rate was recorded using an ECG and mean arterial pressure was mcorded directiy from the btachial artery by use of a catheter. Cardiac output was measured using a dye-dilution technique. Central blood volume (CBV) was calculated from the data. Measurements wen taken upon inflation of the G-suit, 45 seconds into inflation, and 5 minutes into inflation. Gray found that during G-suit inflation at 60' HüT, systolic, diastolic, and mean meriai blood pressure increased and 1 1 % respective1 y. These value returned to control values after 5 minutes. CBV was found to increase 42% upon inflation of the G- suit. This also retumed to normal after 5 minutes. CO inmased 53% dunng G-suit inflation and HR dec~ased 10 beau per minute. These values penisted after 5 minutes. In 1985, Seawonh et al. also studied the effect of G-suit inflation in a 1 G envimnment [32]. Seaworth subjected 10 healthy men to G-suit inflation profiles of 2.4, and 6 psi in using both the supine and upright position. Ventricular volumes were ~corded using two-dimensional echocardiography. Cardiac output, smke volume, and end-diastolic volume (EDV) were calculated hm this measurement. Blwd pressure was recorded by cuff sphygmornanometry to give both SBP and DBP from which MAP was calculated. Penpherai vascular resistance was calculated by dividing MAP by CO. Seaworth found that when the subject was in the supine position, MAP increased significantly for al1 G-suit pressures. Upon defiation of the suit, HR increased and MAP decreased in both the 4 and 6 psi schedules. When in the standing position MAP, EDV,

60 and stroke volume increased with al1 G-suit inflations. When the G-suit was deflated in the standing position these same values decreased Modem G-suit design developments As stated previously in section 2.7, the G-suit has undergone few alterations since its inception 50 years ago. most of which had only minor effects on G-protection. Since modem tactical aimfts are! capable of achieving mater than +9 Gz improved G-suits and pater G-protection for pilots has become a necessity. Recent rnilitary aviation accidents have highlighted this shortcoming in G-protection. To combat this problem, the Canadian Air Force has recently developed STING G-suit. as part of the Canadian Air Force's new STiNG protection ensemble. The STiNG G-suit follows the concept of extended bladder covenge over the lower extremities for increased G-protection. The extended coverage provided by the STING suits works on the principle that increased bladder coverage will cause a larger increase in lower body tissue pressure versus older style, cut-away G-suits. It is believed that this will allow for better maintenance of HLBP under high ffiz and, therefore, increased G- tolerance- Studies have been inconclusive on whether these extended coverage G-sui& actually inmase maximum G-tolerance. However, extended coverage G-suits have been show to reduce pilot fatigue and increase G-tolerance time versus older style Gsuits [23,24]. Also, ment centrifuge and in-flight tests of the CF STING have provided

61 definitive evidence that extended covenge G-suits offer a signifiant increase in protection over standard G-suits when used with PPB as part of a G-protection ensemble [ G-suit inflation: timing and rate of inflation The antig suit inflates when a pilot is exposed to increased gravito-inertial forces. This inflation is controlled by a valve which is G-intensity sensitive. When the pilot experiences high acceleration the valve opens and. using air from the jet engine, the suit inflates. The current, standard G-suit valves are mechanical. When they sense gravitoinertial forces above 2 Gz, they open causing the G-suit to inflate at a rate of approximately 1.5 psi per G to a maximum of 10 psi (141. The +2 Gz dehy is necessary to prevent the G-suit from inflating under circumstances it is not needed such as aircraft buffeting and low G-level moderate tums. In these situations. G-suit inflation can be uncornfortable and distracting to the pilot There has been considerable debate in the field of aviation on when and how rapidly the G-suit should inflate. It seems logical that. since KLBP bcgins to decrease imrnediately with the onset of Gz and that the G-suit provides hypertension upon inflation to counteract this decrease, the G-valve should provide a pressure which coincides with the G-profile. However, studies on this subject have been inconclusive.

62 A comprehensive review of G-suit inflation rate studies has been performed by van Patten [30]. Van Patten shows that scientifie conclusions on optimal G-suit inflation rates have ranged rom immediate, very rapid G-suit inflation as a necessity for increased O-tolerance to those studies that show slower-onset inflation and even a slight delay in the onset of inflation has no il1 effect on G-protection. The ovemding problem was that there wûs linle direct evidence to support any conclusion. A 1997 study perfonned b y Pecûnc. B uick, and Maloan attempted to collect this direct evidence The investigators exposed 8 subjects to rapid onset rate G profiles in the DCIEM centrifuge to a plateau of +5 Gz. Each subject wore an extended coverage G- suit pressurized according to the standard G-valve output schedule. In order to simulate improved or delayed G-valve rrsponsiveness, the authors inflated the G-suit either 0, 1.S. 3, or 4.5 seconds after reaching the +Gz plateau. Beat-to-beat blood pressure was recorded non-invasively using a Finapres BP monitor and light loss experienced by subjects were recorded in order to determine G-tolerance. The investigators found that BP did not increase instantaneously with G-suit inflation. G-protection from G-suit inflation delays of 0 or 1.5 seconds were similar. However, delays of 3 and 4.5 seconds were found to compromise G-protection significmtly. The authors concluded that in order to provide optimal protection. the G- valve should complete the pressurization of the G-suit within 1.5 seconds of the +Gz plateau.

63 3.5.3 Use of the Anti-G suit for protection against the push-pull effat nrneuver Again, there are very few studies which involve the use of the anti-g suit as a protection method against the push-pull effect maneuver. In 1993, Prior, Adcock, and McCanhy performed an in-flight experiment [311. Subjects were exposed to three +4 Gz tums of 15 seconds duration followed by three -2.5 Gz to +4 Gz maneuvers. Two similar sequences were perfomed, with and without O-suit inflation. The artenai wavefonn, systolic, diastolic, and mean artenal blood pressures were recorded using a Portapres non-invasive blood pressure monitor. Prior and colleagues found that artenal BP fell "precipitously" when -2.5 Gz preceded the +4 Gz. thus providing supportive evidence for the previous centrifuge experiment performed by Lehr wd Prior. Pnor also found thit this demase in blood pressure caused by I G transitions was unaided by G-suit inflation. However, the G-suit was found speed the rate of blood pressure recovery compared to unprotected runs. In 1995, Prior reported a push-pull in-flight study [II similar to the one he performed with Adcock and McCarthy in 1993 [311. Rior first exposed his subjects to a flight profile that started at +3 Gz then increased in +OS Gz increments until the subject reported substantial visual disturbances (pyout). Various 43 to +Gz protiles were then flown. The subject was exposed to G-levels of -0.5, -1.O, or -2.5 for 2 or 10 seconds which was followed immediately by +3.5 Gz for 15 seconds. Each subject perfomed approxirnately 6 +Gz profiles and 12 &z transition profiles, Two similar sequences were performed, with and without G-suit infiation. A Portapres kat-to-beat BP monitor was used to measure BP during the expriment.

64 When Prior compared the BP results for the +Gz only versus negative to positive Gz transitions he found that in al1 cases where -Gz preceded ffiz there was a more profound decrease in BP under the subsequent +Gz maneuver. This decrease occurred r~giudless of whether the G-suit was inflated. Since adequate BP is significant to maintaining perfusion of the brain, Prior believed that this fa11 in BP resulted in a deçreased G-toiemce. He thetefore conciuded that ioss of consciousness wouid more readily occur when dunng negative to positive G transitions than in situations where +Gz was experienced aione.

65 4.1 Subjects Recruitment The experiment protocol was granted full approval for use of human subjects from the Defence and Civil Institute of Environmentai Medicine (DCEhQ ethics committee. Subjects consisted of 8 maies and 1 female ranging in age from remited thmugh persona1 contact on site ût the DCCEM. Participation was voluntarily and wu open to both civilian and military DCIEM personnel. Each subject was provided with an information package which outlined the experimentd protocol and the risks. This package also contained consent forms to be signed by the subjects. A copy of this fom is supplied in Appendix D. Each subject undenuent a thorough medical examination by the DCIEM medical sector in order to become qualified for kgz transition exposures. Both medical clearance and subject consent had to be received before participation in the study was granted.

66 4.1.2 Subject Training Al1 subjects were required to attend a 2 hour training session on a sepûraie &y prior to the experiment during which they were introduced to the laboratory. This training also included a comprehensive briefing on the biomedical monitoring equipment, the experimental procedures, and the physiological effects of G-suit inflations and M z transitions. Each training session was conducted by one of the investigators of this study who was knowledgeable in accelention physiology and had experience with G-suit and tilt experiments. This investigator was also fhliw with the medicauphysiologica1 nin temination criteria and had valid CPR certification. Al1 subjects were tnined in a seated position with a STING G-suit. Training with G-suit inflation was aiso performed using the head-down tilt position employed in the experimental protocol Subject restrictions Subjects agreed to: (1) Refrain From alcoholic beverages within 24 hours of the experiment (2) Avoid heavy exercise on the day of the experiment (3) Abstain from smoking, coffee, cola, and chocolate within 3 hours of the expriment (4) Avoid eating a meal within 1 hour of the experiment (5) Avoid a blood donation within 30 days of the experiment (6) Have a restful evening the night before the experiment

67 4.1.4 Su bject characteiistics S ubjec ts' gender, age ( years), height (cm), mass (kg), and heart-to-eye distance (cm) were recorded. Estimates of body surface area (BSA in m') were calculated using the standard Dubois nomograph [70]. Subject characteristics are summaized in Table 5-1 * 4.2 Physiological monitoring and instrumentation The following measurement techniques were used for the present study and have ken used successfully in previous human experimentation at the DCIEM [21 J. These physiological measurements were used to assess transient cardiovascular events and were recorded on a continuous buis. Al1 of the techniques utilised were non-invasive:

68 Table 4-1: Summ~ry of Physiologicai Measunmen&, Techniques and Instrumentation Systolic and diristolic btood pressure (SBP and DBP) Stroke volume (SV), crirdiac output (CO), and base impedance (20) I f o m b l d flow (FBF) Technique Arterial volume clamp piethysmogmphy Electrocrirdiog.mph (ECG) Impeâûnce cardiogrriph (ICI Venous occlusion plethysmopphy I 1 POMPN~, BP rnonitor ~ektronix", single channel electr0cardiogr;im Minnesota, impedance cardiopph, Mode1 304B ~ohnson~, venous occiusion plethysmogmph For the physiological measurements outlined in the foilowing sections, data were collected pre-hdt, dunng HDT, and ai 3 time periods pst-hdt. These periods of collection, referred to as HUT 1, HDT, ma, m b, and HUTZc, are illustmted in Figure 4-1. Figure 4-1 Data collection

69 4.2.1 Blwd pressure Systdic and diastolic blood pressure Instantaneous, bat-to-beat systolic and diastolic blood pressure (SBP and DBP) was obtained non-invasively using a Portapres plethysmographic BP rnonitor (Ohmeda. Mode1 2400, Louisville, CO). The Portapres consists of a servo control unit and a pneumatic finger cuff which operates based upon a technique developed by Penaz [SI]. This technique relates digital ûrtery size and the finger cuff pressure required to maintain this size to orterial blood pressure. The Portapres controls finger cuff inflation (and therefore artery size) using blwd flow input fmm the phototmitter and recorder embedded in the cuff. Using these measurements and algorithms present in the control unit. the Portapres is able to provide non-invasive, instantaneous, bat-to-beat BP measurements. Validation studies have show systolic and diastolic blood pressure measurements reported by the Portapres to be well correlated with intra-artenal pressure recordings (r ) [52.53]. The fmger cuff was fitted to the middie phalanx of the second finger of the left hand. It was then positioned on the chest at the level of the third intercostal space to monitor hem-level BP. The left hand was secured by Velcro strapping to minimize movement during tilt. BP was continually monitored for any imgularïties. If abnomali ties were detected and believed to pose a ris k to the subject, the expriment was tenninated.

70 The Portapres unit has an Auto-Cal option which automatically calibrates the unit every minute. To avoid calibration interruptions mid-run, the Auto-Cal feature was turned off irnmediately prior to each experimental run. Custom, in-house UNIX-based software was used to identify discrete SBP data points and their subsequent DBP values on û digitized Portapres waveform. The software then calculated mean artenal blwd pressure (MAP) using the following equation: Equation 4-1 MM = DBP + 1/3 (SBP - DBP) SBP at heart-level was corrected to head-level by applying the following equation (as seen in section 3.1.1): Equation 4-2

71 Vertical hem-toeye distance (h) was measured with the subject sitting in the upright position on the tilt table. In this position, G is equal to the acceleration due to gnvity (9.8 ms'?. Since the tilt table is always positioned at 15' HUT and 135' HDT, trigonometry cm be used to calculate what h and G are at these angles: at 15" HUT PM = Pb-pGh HLBP = Pb- (1113.1)[(COS 15")(9.8)][(~0s LSo)(h)l = P, - (0.698)(h) at 135" HDT, P =P-+pGh HLsP = Pm+ (V13.1) [(sin4s0)(9.8)j[(sin4s0)(h)] = P, + (0.374)(h) Heart rate An device (Tektronix, Type 408, Beaverton, OR) was used to continuousl y monitor hem rate (HR) and electricai activity. ECG electrodes were placed in a three point fashion; one adhered below each clavicle and one at the V5 position on the left si&. ECG was continually monitored in order to identify any ECG

72 wavefom imgularities. If any abnormalities were recognized and believed to pose a risk to the subject, the expriment would be imrneâiately terminated. Stroke volume (SV), cardiac output (CO) and base impedance (Zo) were estimated using the technique of impedance cardiography (IC). Validation studies have show SV and CO measurements by IC to be well correlated with values reported by other techniques such as Thermo- and Dye-dilution (up to r = 0.88 for SV; up to r = for CO) [SJ,SS.69]. Four circular band electrodes were placed on the subject: 2 a n d the neck and 2 amund the tono as described by Kubicek [54]. The bands were connected to an Impedance Cardiograph unit (Minnesota Impedance Cardiograph, Mode1 304 B, Minneapolis, MN) and values for base impedance (20) and dzldt were collected. Custom, in-house calculation software used raw ECG. Zo, and dddt values to compute estimated values for Stroke Index (SI, stroke vol. in mllbeatkg body wt.), Cardiac Index (CI, cardiac output in mllrninlkg body wt.). An estîmate of total peripheral resistance was computed by dividing MAP by CI. The result was a calculation of the total peripheral resistance index V Ri, in mmhg/murnin/kg body wt.).

73 4m2m4 Venous Occlusion Plethysmography The venous occlusion plethysmography technique has ken performed in numerous studies and is described in a comprehensive review by Whitney [56]. In this study, venous occlusion plethysmography was used to measure foream blood flow (FBF) and to caicuiate forearm vascular resistance (FVR). While seated on the tilt table, the subject's nght am was extended and secured in front of their body at hem level using an adjustabie, custom made support. Forearm venous occlusion was obtained by infiating a blood pressure cuff around the upper nght arm to 50 mmhg (approximately upper arrn venous pressure) using a Hokanson npid cuff inflator (D.C. Hokanson Inc., Model E-20, Issaquah, WA). When venous flow was occluded, foreami girth increased due to artenal foreann blood flow (FBF in mm/ lûû ml tissue). The greater the amount of FBF, the pater the change in girth observed. Forearm girth was recorded using a commercially-available saain gauge made of a thin, double-stranded. hollow si lastic nibber tube filled with rnercury (Hokanson, Bellevue, WA). The suain gauge was placed around the nght forearm at the point of largest circumference, approximately 15 cm fmm the elbow. When the gauge was stretched or contracted the meirury inside the gauge changed resistance. This change in resistance was measured by Hokanson plethysmograph unit (Hokanson, Model EC-4. Bellevue, WA) which translated this change in resistance into a change in voltage. This output was recorded on a chut recorder (Gould, Model RS 3600, Cleveland, OH). The slopes of these changes in voltage were then measured by hand and entered into a formula to calculate FBF in müloomi of tissue/min (see Appendix E for calculation). One FBF

74 measurement was taken at pre-hut, one during HDT, and 3 during pst-hut as per Figure 4-1. When in the HUT position, the gauge was at hem-level. Therefore, the vertical distance between these two points was zero. Therefore, using Equation 4-3, the BP at the gauge (foream mean artenal pressure, fmap) equaled hem-level blood pressure (as measured by Portaprcs). Equation 43, p =fmap=p,+pgh if h =O, fmap=, P + pg(0).. fmap=, P In the 13S0 HDT position. the gauge is no longer at the level of the hem. Therefore, heart-to-gauge distance (h) was measured in the HDT position. tmap was then calculated using Equation 4-3. FVR was then caiculated by dividing fmap by forearm blood flow (fmapifbf = FVR in mmhg/mu 100rnl tissuelmin). FVR calculations were performed on the same schedule as FBF measurements, as per Figure 4-1.

75 43 Subjective measurements Visuai light loss Subjective mesures for visual disturbances wen perfonned using a lightbar custom made for the DCIEM tilt table. The lightbar was placed at eye-level, 40 cm in front of the subject. It consisted of a centrally located red light and two bilaterai green lights (22 cm from centre) on a 75 x 25 cm black background. Traditionally, peripheral light loss (PU) and central light loss (CLL) perceived by the subject have ken considered the standard subjective measurements of the gravityinduced symptoms of greyout and blackout respective1 y [14]. After each run, the subject w u asked if they had any PLL or CIL visuai disturbances. The results were recorded by the investigators Other subjective measurements In order to gain insight on the effect of tilt and G-suit inflation the subject was asked a series of questions following each nin. Qualitative cornments regarding facial congestion, breathing difficulties, pain caused by the G-suit, and any additional observations were recorded by the investigators.

76 4.4 Equipment Tut table The DCiEM electronic tilt table was used to simulate the push-pull maneuver. The subject was seated on the tilt table and secured using a four point hamess, custorn fmt restraints, and custom shoulder pads. Push-pull was then simulated by placing the subject at an angle 15' HUT followed by L 35" HDT for 15 seconds then a retum to 15' HUT. This method has been used successfully in previous studies [21] Anti-G suit and pressun delivery system The STING anti-g suit was used in this experiment since it is generally recognized by the Canadian Department of National Defence as the latest in G-suit technology for G-protection. The G-suit was custom fitted for each subject by a DCIEM expert in STiNG suit tailoring. Once the subject was secured on the tilt table, the G-suit was connected to a custom-made. computerized inflation system. A diagram of the system is provided in Appendix F. G-suit inflation was performed using a compressed air pressure source which was fed through a computer controlled SAMCAV valve. The computer could control initial onset of inflation, onset rate, and maximum inflation pressure in accordance with di fferentl y pre-programrned G-sui t schedules.

77 To conaol initial onset time of SAMCAV valve inflation, the computer was fed the position encoder signai from the tilt table. Tilt angle could then be interpreted by the computer software thus allowing the computer to time G-suit inflations to the tilt angle. The computer could then perform the correct initial inflation time for the selected G-suit SC hedule. The computer couid control maximum inflation pressure by switching between a normal (2 psi) or high (3 psi) pressure line connected to the SAMCAV valve through a 3 way 'Y' tube. This allowed the computer to provide the appropriate pressure for each G- suit schedule. In order to ensure inflation was accurate, G-suit pressure was continually rnonitored and corroborated by the investigators through the use of o digital pressure transducer (Validyne, Model PS 309. Nonhridge, CA). The computer controlled inflation onset rate by adjusting rotational position of the SAMCAV valve. By controlling the position of SAMCAV, the cornputer could control the speed at which the SAMCAV valve opened and. therefore, control how much air was allowed to inflate the G-suit. The computer could then perfonn the inflation rate that was necessary for eac h pn-programmed G-sui t SC hedule. For safety considerations, a mechanical pressure relief valve was used to protect from G-suit overpressure. If pressure were to inadvertently increase above 4 psi, the relief valve would open venting the system to the atmosphere. For added safety, an electronic odoff switch was located on the pressure apparatus for the investigators to stop the experiment. The subject was also proviàed with a hand-held 'kill' switch to be used in case of emergency.

78 4.5 Experimentai Design In order to avoid &y-to-day variations in physiological responses. the experiment was conducted in a single session of approximately 2 hours in duration. Afier king prepared and secured to the tilt table, subjects completed one session consisting of preplanned tilt-table motions and G-suit inflations Oder of expriment: Tilt table profile and Experimeatal schedules (1) Pre-experiment rest periad Wearing a non-pressurized G-sui t. the subject was placed at 15' HUT for 3 minutes. While the subject relaxed, ECG. b l d pressure (BP). and impedance ciirdiography (IC) &ta were observed to verify the quality of physiological signais. One forearm blood flow (FBF) measurement was performed to properl y sent the inflation cuff on the upper m. (2) Pre-experiment unprotecteà nin After 3 minutes of rest, the subject was placed in the 15' HUT start position. To rnirnic the PPEM, the subjects were then tilted to 13S0 HDT for 15 seconds after which they were retumed to 15' HUT (see Figure 2-5 and Table 54). During this time, ECG, BPT IC and FBF were collected as per sections

79 (3) G-suit inflation runs Tilt table motion profile parameters were the sarne as in the unpmtected run. however, subjecis were exposed to various G-suit inflation schedules which were varied by : (i) initial inflation onset time [either during transition to HUT 2 or upon reachiag KUT 21 (ii) onset rate [approx. 1 second (normal) or approx. 2 seconds (slow)] (iii) maximum inflation pressure [2 psi (normal) or 3 psi (high)] For each G-suit inflation nin, ECG. BP, IC and FBF were collected as per sections Between mns. subjects were given 2 minutes of rest to allow for recovery. These various inflation schedules are summarized in Figure 7-5 (section 7.13) and Table 4-2 (next page).

80 Table 42: Tilt table profile and Experimentai schedules G-suit inflation SC hedule. Tilt table transition duration tilt angle dmtion rit HDT dmtion of inflation pressure (psi) Comments I Unprotected PnDTr (=) ("1 (=cl - dwing transition to HUT (=) F O inflation omal inflation me, ormnl prcssure (?psi) PsDTr orrnd pressure PnUR ormal pressure r PhUR 3 F omal inflation rate, igher pressure 3psi) For explanûtion of schedule codes see Table 2-1 (section 2.12). (4) Post-expriment unprotecteû mn-same procedure as (2). 0 (5) Post-expriment mt period -same procedure as (1). Total Numùer of Experimcntaî Scheâuks: Unprotected nins (pre and pst) G-sut nation S.....4

81 4.6 Data Analyses It should be noted that for the purpose of analysis: (1) Pre and post unprotected runs will be referred to collectivel y as "unprotected schedules". (2) RiDTr, PsDTr. PnüR, and PhüR mns will be collectively be referred to as "G-suit inflation schedules" or "protection schedules". (3) Al1 nins (unprotected and protection mns) will be collectively referred to as "Expenmental schedules" dp and dt for Systolk Blood Pressure (SBP) To avoid the effects of anticipation, SBP data from the initial HUT phase (HUTl, see Figure 4-1 for tilt phases) was averaged for a 10 second pend which kgan 20 seconds befo~ the HDT phase and concluded 10 seconds before the HDT phase. During subsequent HUT (HUTZ), the minimum BP and the point of 90% recovery of BP (90% of the calculated initiai HUT BP) were recorded. The ciifference between the initiai HUT BP (HUTI BP) and the minimum subsequent HUT BP (HUT;! BP) was recorded as dp. The time to 90% BP recovery was recorded as dt Both dp and dt for dl subjects were then analyzed in separate one-way analyses of variances ( M A S ) using statistical analysis software (Statview v. 4.5, Abacus Concepts Inc., Berkeley, CA) to detect any main effect

82 of different experimental schedules. Scheffe's pst-hoc test (d.05) was then used to detect if significant differences existed between experimental schedules. Results for dp and dt are presented in graphical fonn in section 5 as side-by-side histograrns. Histograms present Mean 2 1 Standard Error of the Mean (SEM) for each experimental schedule SBP, MAP, HLBP, HR, Zo, SI, CI, TPRi, FBF, and W R Vaiues for SBP, MAP, HLBP, HR, Zo, SI, CI, TPRi, FBF, ruid FVR from dl subjects were recorded andfor calculated for er h experimentd run at the HUT 1, HDT, HUT2a, HUTZb, and HUT2-c positions. In order to control for individual variation, these vdues were expressed in 'percent changes' (%A) by dividing the values at HDT, HUT2a. HUT2-b, and HUT2c by the values recorded for HüT 1 and multi pl ying by 100. Percent change values for the HDT position were analyzed using r one-way factorial ANOVA to detect any main effect of experimental schedule. A pd.05 was considered significant. If significant diffennces were detecied, Scheffe's pst-hoc test (cd).05) was used io determine if significant differences existed between experimental schedules. All ANOVAs and pst-hoc tests were perfomed using commercially available statistical software (Statview v. 4.5, Abacus Concepts Inc., Berkeley, CA). To analyze immediate (within 5-10 seconds of the initiation of HUT2) reactions to the tilt table simulated PPEM, percent change values for the HUT2a position were analyzed using a one-way factorid ANOVA to detect any main effect of experimental schedule. A p8.05 was considered significant. If significant differences were âetected,

83 Scheffe's pst-hoc test (&.OS) was used to determine if significant differences existed between expenmental schedules. Again, ANOVA and pst-hoc tests were performed using commercially available statistical software (S tatview v Abacus Concepts Inc., Berkeley, CA). To analyze long term (5-40 seconds after initiation of HUT2) actions to the tilt table simulated PPEM, sepwate 3 (position- HUTZb, HUTZc) by 6 (expenmental schedules) repeated measures ANOVAs were used to detect any main effect of expenmental schedule, main effect of the time after HDT, and any interaction between expenmental schedules and the data. A p4.05 wm considered signi ficant. If si gni fiant differences were detected, Sche ffe's pst-hoc test (d.05) was used to determine if significant differences existed between experimental schedules. Al1 tests were performed using commercially avûilable statistical software (Statview v Abacus Concepts Inc., Berkeley, CA). Results for each variable are displayed in graphical form as line graphs in section 5. Graphs present Mean I SEM for each experimental schedule. After the &ta was initially analyzed using the criteria listed above it was discovered that the pre and post unprotected runs were not significantly different for al1 tests performed. Therefore, the data was re-analyzed using a pooled value for the unprotected runs. The nsults are presented in the mxt section in the sarne method as

84 explained above. HDT and HUna still used one-way MVAs however the repeated measures ANOVA on the HUT2a-c positions was now a 3 by 5 ANOVA (one less experimental schedule due to the pooling of unprotected cesults).

85 Note: (1) Examples of strip recordings for each schedule appears in Appendix A (2) Al1 ANOVA tables and corresponding Scheffe's pst-hoc ~sults can be found in their entirety in Appendix B. (3) An inter-subject cornparison of absolute changes in SBP, HLBP, and HR can be found in Appendix G. 5.1 Subjects Subject characteristics are summûnzed in Table 5-1 : Table 5-1 Subject choracteristics 1 - Male 2 Male 3 Female 4 Male 5 Male 6 Male Height Icm) O Mass Heart-to-eye dist. (mi) O 30.0 Body Surface Area (m2)

86 Al1 9 subjects complied to the restrictions outlined in section Experimentai conditions were well tolerated with no subjects experiencing light-loss. diwiness, motion sickness, or other pre-syncopa1 symptoms. The investigaton did not recognize any grossly abnonnai signals andor responses from the subjects that would pose a risk to subject hedth or require the termination any experimental runs. 5.2 Systoiic Blood Pressure 52.1 Decrease in SBP (dp) The resulting one-way ANOVA for the immediate decrease in SBP (defined previously as dp) associûted with the transition to HUTZ reveded: a significant main effect of experirnentül schedule rf(4.32) = ~=û.o014]. r Scheffe's post-hoc test found a significant di fference between (1) Unprotected and PnDTr (p=0.0071), (2) Un protected and PsDTr (pc0.0085). (3) Unprotected and PnUR (pc0.0487). No other significant differences were detected. An examination of Figure 5-1 illustrates that there was less of a decrease in SBP for runs involving G-suit inflation when cornpared to the Unprotected schedule. Alihough there was large variability in the data there was less of r decrease in SBP for PnDTr and PsDTr runs when compared to PnUR and PhUR runs.

87 Figure 5-1 Lkfrcppe in SBP (dp) Meaa 1 Standard Emr of the Mcan (SEM) Unproreccd- No inflation. mt;ui of prr and pst Unpmtccted mm: MC: Pressure noml. inllation During Transition m HUE: RDTr: Pressure noml. slow inflûtion lhuing Triansition CO Hm: PnUR RMsurc mml. inflation Upon Rmching HUR: PàUR: Rtsswt high, inflation Upon Rc;iching HUTZ Tirne of SBP recovery (dt) The resulting one-way ANOVA for time of SBP recovery (âefined as dt) reveaied: a a significant main effect of experimentai schedule F(432) = 8.322, pi a Scheffe's pst-hoc test revealed significant diffmnces between (1) Unprotected and hür (p=0.0112),(2) Unprotected and PhüR (pc0.006). No other significant differences were detected

88 .--A-.-A..--. A &+.. Figure 5-2 illustrates that SBP undenuent a faster recovery for mns involving G- suit inflation when compared to the Unprotected schedule, however, there was a great deal of variabili ty between al1 experi mental schedules. Compared to the Unprotected xhedule, PnUR and PhUR inflation schedules resulted in a fastet SBP recovery than the PnDTr and PsDTr schedules. Figure 5-2 m4 * h e of SBP recovery (dt) Mean t SEM :: L ;,. ;;'.. " :.. $ G.:,.,: ;i[,y:4. i +.,,;, 1 PhUR ' - : :!!, :::.,.;:.::,,,, &th:?* ,:..,..! * *., k,.,r:!;; a. :::.:.:..:::.::::., :,:;,, ,, :,. i4 iii::fiiiiiii9 t'...ri *,... ~l~~i,~~,~lt~~l,,.;: 1:;;,, i//iliilii, < ::::,y;-:;:;::;:;::;::: ilil : ; ; y-;ir;ixiii;gi!i;i '4. j,..,.. i h.! l., 7 :::- :~~:::~::~::~::~:: Iil z:::,.: ::-: z:::;:,. '1 ;:;, :,:::::::,:::=:y:;, 1 i.l..-li, , * *--.?'i1,.1.:,,; , -* *.* ; ld il l!!ii- Unpro(ccM: No inflation, m n of pre and post Unprotecttd runs; Mt: Pressure normal. inhtion During Transition to HUTZ: Pressure noml. slow inhtion Ihuing Trrinsition to HüT2: Pnük Rcsswe #Miul. infiaiion Upoa bûiag H m PhUR Pressure high. infitioa U~ML hching Hm Slstiilicrl b otah %t HUTZa: Unpmtcctcd vs. PnUR. Iinpmcracd a. PhUR

89 5.23 Repeated measuros ANOVA for petcent change in SBP The one-way NOVA on HDT for the percent change in SBP (%ASBP) vs. HUTl reveded: r significant difference between experimental schedules F(4.32) =3.757, p =0.0129]. Scheffe's pst-hoc test detected a significant difference between (1) Unprotected and PhUR (p=0.0496),(2) PnUR and PhUR (pc0.0476). The one-way ANOVA on HUna for the %ASBP vs. HUTl reveded: r a signi ficant di fference between experimental schedules F(4.32) =8.088, p =û.oûû 11. r Scheffe's pst-hoc test detected significant differences between Unprotected and dl G-suit inflations (ail p-values d.0157). No other significant differences were detected. The resulting 3 (position -HUT Za, HUT 2b, HUT 2c) by 5 (experimentd schedules -Unprotected, PnDTr, PsDTr, PnUR, PhUR) repeated measures ANOVA for the BASBP for HUT 2a, HUT 2b. and HUT 2c vs. HUTL revealed the following: a significant main effect of expenmentai schedule F(4,64) =6.498, p r a significant effect for tilt position (time after HDT) F(2.64) =75.120, p <0.0001] * a significant Zway interaction of experimental schedule and tilt position P(8,M) =2.599, p ==û.0159].

90 Scheffe's pst-hoc test reveaied significant differences in %ASBP between (1) Unprotected and PnDTr (p=0.0340),(2) Unprotected and PsDTr (p=û.o99),(3) Unprotected and PnüR (p=û.0024). No other significant differences were detected. As Figure 5-3 illustrates, SBP demased slightly at HDT, decreased significantly at HUT2a, then recovered back towards normal dunng HUT2b and HUT2c. The decrease in %ASBP was less at HUI' 2a. HUT 2b, and HUT 2c for ans involving G-suit inflation versus Unprotected. No difference within Gsuit inflations was apparent. U o p m No ~ inflation. mean of pte and p t Unpmtcctcâ ruas: RiDTr: Rusure mmi, infiation During Trimition CO HiJi2 RDk PRSSW nord. slow inflation ihuing Transition m Hm; PhUR: hssurc hi& inflation Upoa Rci~~hing HU72 S(idst&!aIdemcathm FOUR: Rruw mnd inihtion Upon Rc;iching HUïZ

91 53 Mean arterial biood pressure The resulting one-way ANOVA on HDT for the percent change in MAP (%AMAP) versus HUT 1 data revealed: 0 a significant differences between experimental schedules p(4,32) = p = However, Scheffe's pst-hoc test did not detect any significant differences between experimental SC hedules The resulting one-way ANOVA on HUTîa for the %W versus HUT 1 data. 8 data cells were corrected due to compt or missing data. The one-way ANOVA revealed: 0 a significant di fference between experimental schedules F(4.32) =L p<o.oo 11. Scheffe's pst hoc test detected signi ficant differences between Unprotected and ai 1 G-suit inflations (al1 p-values < 0.035). No other differences were found. A 3 by 5 npeated measures ANOVA for the %AMAP for HUT 2a. HüT 2b, and HUT 2c vs. HUT 1 revealed the following: a significant main effect of experimentai schedule [F(4,64) =8.566, p ] a significant effect for tilt position (time after HM') F(2,64) = p ] a significant 2-way interaction of experimental schedule and tilt position F(8,64) =4.555* p =0.0002] Sc heffe's pst-hoc test found a significant difference in %&Mi? between Unprotected and ail G-suit inflations (al1 pvalues c0.0190). No other significant differences were found.

92 Inspection of Figure 5-4 illustrates that MAP decreased slightly at HDT, decreased significantly at m a, then recovered back towards normal dunng HUT2b and HUT2c. The decrease in %W was less at HUT 2a, HUT 2b, and HUT 2c for runs involving G-suit inflation versus Unprotected runs. No ditference within G-suit inflations is apparent. Figure 5-4 Rirent change in MA P Mean & SEM Unprdcrccd: No inflation. mm of prr and post Unproucicd runs; PuiYi'~ hure mml, inflation During Transition to Hm PsDTr: R#swc normal. slow inflation During Transition to HLPIU; RiUE Presstue m d infiarion Upon Reading Hm: PûUR: Rcssurc hi@. inflation Upon Rmcùing Hüï2 SîatWd denota* * r HVRi: Unpooeild vs. MYh. Unpmmcd vr Rmr. Uopmtrnrd vs. PsUR. Unpmccncd vs. RUR:

93 5.4 Head-level blooà pressure A one-way ANOVA on HDT for the percent change in HLBP (%LSHLBP) vs. HUT 1 data revealed: a a significant difference between experimental schedules F(4.32) = p =0.0029]. a Scheffe's pst-hoc test detected a significant difference between PnUR and PhUR (p=0.0042). No other differences were detected. A one-way ANOVA on HUna for the %-P vs. HUT 1 data revealed: 8 a significant di fference between experimental schedules F(4,32) =7.548, p =CL00021 Scheffe's post-hoc test detected si gni ficant di fferences between Unnprotected and al1 G-suit inflations (al1 p-vaiues c 0.028). No other significant differences were found. The resulting 3 by 5 repeated measurrs ANOVA for the %=P for HUT 2a, HUT 2b, and HUT 2c vs. HUT 1 revealed the following: a significant main effect of experimental schedule rf(4.64) = p =0.0006] a significant effect for tilt position (time after HDT) [F(2.64) = p ] a significant 2-way interaction of experimental schedule and tilt position [F(8,64) =69.426, p =0.0425] Scheffe's pst-hoc revealed a significant difference in %AHLBP between (1) Unpmtected and PROTr (p=0.0362),(2) Unpmtected and PsDTr (ps0.0184). (3) Unpmtected and hur (p=o.ûû 16). No other differences were detected

94 Figure 5-5 illustrates that HLBP increased significantly upon HDT, demased significantly during HUT2a then recovered towards normal values during HUT2b and HUT2c. %AHLBP decreased less at HUT 2a, HUT 2b, and HUT 2c for cuns involving G- suit inflation versus Unpmtected. There was no visual ciifference within G-suit inflation runs. Figure 5-5 Percent change in HLBP Mean I SEM % change hm 20 HUT1 10 O + Unprokaal U PnDTr -0- Palk P nur PWR tldt HUT2a UUTZb HUTTC Tilt pmit bn Unproiccîd: No inflation. mean of prc and pat Unpmtccted Nns; ~rrrsure mrm;il, inflation hiring Tmition to Hül2: Mt Fressure nom[. slow inflation During Transition io HUE; PnUk R#surc w ~ inflation. Upon kching HU77: PûUR: h u w bigh. inflation Upoa Rnching HVP, drnototlom * u ~ m: RIUR vr. RUR: ** ri HLKIX ~nprotcctcd n RM~. unpmimed vs. RDT~. ~npmcc~

95 5.5 Heart Rate The resulting one-way ANOVA on HDT for the percent change in HR (%AHR) versus HUT 1 data nveded no significant differences between exprimental schedules F(4,32) =û p =0.9322]. The resulting one-way ANOVA on HUT2a for the %AHR versus HUT 1 data revealed: a a significant di fference between experimental schedules p(4.32) =3.984, p =0.098]. a Scheffe's post-hoc test detected a significant difference between Unprotected and PnüFt (pd.036). No other significant differences were found. The 3 by 5 repeated measures MOVA for the ZAHR for HUT 2a. HUT 2b. and HUT 2c vs- HüT 1 revealed: no significant main effect of experimentai schedule F(4,64) = p d a a significant effect for tilt position (time after HDT) F(2,64) = , p =0.0008] a no significant 2-way interaction of expenmental schedule and tilt position F(8.64) = p=û.0545]. An examination of Figure 5-6 illustrates that HR was decreased at HDT, increased at HUT 2a, then dec~ased back towards normal during HUT 2b and HUT 2c. Runs involving G-suit inflations experience less of an increase in %AHR during HUna compared to the Unprotected schedule. No diffe~nces within G-suit runs were apparent.

96 Figure 5-6 Percent change in Heart Rate Mcan î SEM HDT HUT2a HUTib HUT2c 'îilt posiîîon Unprotectcd: No innotion, m m of pre and post unprokctrd mas; MC: Rcssurr normal. inflation Dwing Tnwition io HUT;?; RDTr: h ure normal. slow inflation During Tmnsitioa to HUE: RiUR: Pressure aoml, inflation Upon Rmching HUTZ: PbUR: Ressm bigh. infiacion Upon kching HUE SUlitical &notation: * ar Hm: Unpmtccled vr. FnUR 5.6 Base impedance (20) The multing one-way ANOVA on HDT for the percent change in Zo (%&) versus HUI' 1 data reveaied: a significant difference between experimental schedules F(4,32) ~2.672, p =û.0498]. however, Scheffe's pst-hoc revealed no significant ciifferences.

97 The resulting one-way ANOVA on HDT for the %Mo venus HUT 1 revealed: a significant difference between experimentai schedules [F(4,32) =50.536, p~o.ûûûl] a Scheffe's pst-hoc test detected a signi ficant difference between Unprotected and dl G-suit inflation runs [PnDTr, PsDTr. PnUR. and PhUR (dl p-values cû.0001)], It also reveaied a significant difference between RiDTr and PhUR (p=0.0306). Then were no other significant differences. The resulting 3 by 5 repeated measures ANOVA for the %A20 for HUT 2a. HUT 2b, and HUT Zc vs. HUT 1 revealed the following: a significant main effect of experimental schedule F(4.64) =63.073, p ) a a significant effect for tilt position (the after HDT) [F(2,64) = , p ~ a a signi ficant 2-way interaction of experimental schedule and tilt position F(8.64) =3.59 1, p=û.ûû 171 a Scheffe's pst-hoc test detected a significant difference in %Mo between Unprotected and ail G-suit inflation wns [PnDTr, PsDTr* PnUR, and PhUR (al1 p values cû.oûû1)j. There was no significant difference within any G-suit inflation runs. Figure 5-7 illustrates that Zo was significantly decreased at HDT then increased towards normal values dunng HUT Zr, HUT 2b. and HUT 2c. Runs involving G-suit inflation have significantly lower %A20 values during Huma-c versus Unprotected. No difference within G-suit runs was observed

98 Figure 5-7 Pemnt change in Zo lczlm SEM llit position Uaprotccteâ: No inflation, mean of prc and p t uapmtcctcd mm: ML? Pressure mml. inflation hiring Transition IO HUE. PsDTr: Rcssurc noml. slow inthtion During Transition to HUE; FnUR: Rcssurt mml. inflation Upon Reaching HUT2; PhUR: Rcssurc hi@. inflation Upon bching HUT2 SimWcll dcmtüror * rt Hm: Unprotecicd vs. PnûTr. Unpmtecud vr RMr. Unpmtectrd vs. PnUR Unpmtcctd vr. PhUR PnDTr VS. PhUR: ** aaou HU1Z1-?c Unpmtmcd vs. RiDTI. Unpmtcctcd vs. RMi. Unpmiected vs. PnUR Unpmmted VS. PhUR 5.7 Stroke Index The resulting one-way ANOVA on HDT for the percent change in SI (%AS0 venus HUT 1 data revealed no significant difference between experimental xhedules F(4.32) =û.999. p =û.4223].

99 The resulting one-way ANOVA on HUT2a for the %AS1 versus HUI' detected no significant difference ktween experimentai schedules F(4,32) =l. 186, p =0.3359]. The resulting 3 by 5 npeated measuns ANOVA for the %AS1 for HUT 2s HUT 2b, and HUT 2c vs. HUT 1 reveded: no significant main effect of expenmental schedule F(4.64) = p =0.1793] no significant effect for tilt position (time after HDT) p(2,64) = 0.066, p no significant 2-way interaction of experimental schedule and tilt position F(8.64) =1.727, p =û.1092]. Figure 5-8 illustrates that SI increased dunng HDT then decreased towards normal during HUT2a-c. There were no differences between experimental schedules or within G- suit inflations,

100 Figure 5-8 Percent change ia SI Mean t SEM Unpro(cetcd: No inflation, mmn of pre and posi unpmtcctcd mns: RiDTf: Pressure normal, inflation huing Tmition to Hm: RDTE Pressure normal, slow inflation During Transition to HUTS,: PnUR: Pressure mnnnl, inflation Upon Rmching HUT2: WUR: Ressure hia. infhtion Upon Rmching HUT> 5.8 Cadac Index The resulting one-way ANOVA on HDT for the percent change in CI (%AC0 versus HUT I data detected no significant differences between experimental schedules p(4.32) d.683, p = The resulting one-way ANOVA on HUna for the %AC1 versus HUT 1 revealed: r a significant difference between experimental schedules F(4,32) =3.430, p =û.o192].

101 Scheffe's pst-hoc test detected a difference between RDTr and hür (@.O47 1). No other significant differences were found. A 3 by 5 repeated measures ANOVA for the %AC1 for HUT 2a. HUT 2b, and HUT 2c vs. HUT 1 revealed the following: no significant main effect ofexperimentd schedule F(4,64)= p =û.ii63] a significant effect for tilt position (time after HDT) p(2.64) = , pc0.0008) a significant 2-way interaction of experirnentai schedule and tilt position F(8,64) = p =0.0004]. Figure 5-9 illustrates that CI inmased at HUT 2a, then decreased back towards normal for HUT 2b and HU?' 2c for dl runs, PhUR had increased values at HUT3b and HUnc when compared to other experimental schedules. RUR had lower HUT2a vaiues versus other experimentai conditions. No other differences were apparent.

102 Figure 5-9 Percent change in CI Mern *SEM MDT ~IUl2a HWt2b Tilt position Uiipro(rc(cd: No inflation. mean of prc and pst unpmectcd nins: Mr: hure mml, inhtion huing Transition to Hm: RDTr Rnsurc normal. slow iohtion During Transition to Hm PhUR: Rcssurc high. inflation Upon Rcaching HUTL PaUR: Pressure mrml, infiacion Upon hching HUTt: 53 Total peripheral resistance index The resulting one-way ANOVA on HDT for the percent change in TPRi (%ATPRi) versus HUT revealed no significant difference between experimental schedules p(4,32) = p d

103 The resulting one-way ANOVA on HUT2a for the %ATPRi versus HUT 1 data revealed: a a si gni ficant difference between experi mental SC hedules p(4.32) = p =0.0008] Scheffe's post-hoc test found a significant difference between Unprotected and PnCTR (p=û.0ûû9). No other significant differences wen detected. The resulting 3 by 5 repeated measures ANOVA for the %ATPRi for HUT 2a. HUT 2b. and HUT 2c vs. KüTl revealed: no significant main effect of experimental schedule [F(4,64) =l. 177, p d a significant effect for tilt position (time after HDT) F(2.64) = p co.ûûûl] a significant 2-way interaction of experimental schedule and tilt position F(8.64) =4.904, pd.oool]. An examination of Figure 5-10 illustrates that TPRi decreased at HDT and decreased even funher at HUT2a before recovering dunng HUT2b-c. Values for TPRi decreased less at HUT 20 for the G-suit inflations (especially PnUR and PhUR) versus Unprotected.

104 Figure 5-10 Rrcent diange in TPRl Mean*SEM HDT HW2a HUT2b HUTk nit position UnproWctmk No intlation, mean of pre ;md pst unprotecicd mm; PnMr Pmsw mml. inflation During Tnnsition to Hm: PsDTr: Pmsurc noml. slow inflation During Tr;uisitioa to HüT?: PnUR: Rcwurc mnmil inflation Upoa bching HUTI; &UR: h u r e hi@. inflation Upon bching HUTL 5.10 Forearm blood flow The resulting one-way ANOVA on HDT for the percent change in FBF (BAFBF) versus HUT 1 data detected no significant differences between experimental schedules F(4,32) d.762, p =0.5577]. The rrsuiting one-way M V A on HUT2a for the BAFBF versus HUT 1 revealed:

105 a significant ciifference between experimental schedules F(4,32) = p =O.a007] Scheffe's post-hoc test detected a significant difference between (1) Unprotected and PhüR (p=0.0182).(2) PnDTr and PhUR (p=0.0142),(3) PnUR and PhUR (p=0.0345). No other signi ficant difference were found. A 3 by 5 repeited mesures ANOVA for the %AFE#F for HUT Za. HUT Ib. and HUT 2c vs. HUT 1 revealed the following: a significant main effect of experimental schedule F(4'64) =8.601, p<0.0001] a significant effect for time after mt F(2,64) = , p=û.0ûû4] no significant 2-way interaction of %AE%F and experimental schedule [F(8.64) =2.623, p =0.0150] Scheffe's pst-hoc test detected a significant difference in 96AFBF between ( 1) Unprotected and PhüR (p d.0001). (2) PnDTr and PhUR (p=0.0178).(3) PsDTr and PhüR (p=0.0424). No other si gni fican t di fferences were found. Figure 5-11 illustrates that FBF increased dunng HDT and HUT2a before retuming towiirds normal values during HUT2b-c. FBF was elevated for the O-suit inflation mns during the HUT2a-c positions (especidly HüT2b-c) when compared to Unprotected. PhUR values for %AFBF were increased when compared to ail other experimental schedules at dl HUT;! data points.

106 Percent change in FBF M m î SEM Unprotected: No inflation, man of pre and post unpmtccud mns: ~~DTII Pressure md, inflation Dunng Tnnrrition to HUE: PsDTc Rcssurc nord, slow inhtion During Transition to Hm: PnUR: RLssw normal. inflation Upon bching HUT2 WUR: Rcssurc hi@. inflation Upon kching HUTZ StatMW denotation: * at Hma: Unprotateci vs. PhUR PnDTr vs. niur, hur and PhUR; ** anws HüT2ui-Ic Unprotmcd vs. RUR, RDTr vs. PhUR RDTr ûad PhUR The resulting one-way ANOVA on HDT for the percent change in FVR (96AFVR) versus HUT 1 data revealed no significant difference between experimental schedules [F(4-32) = p =0.0701].

107 The nsulting one-way ANOVA on HUna for the %AFVR versus HUT 1 revealed no significant di fference between experimental SC hedules F(4,32) = 1.OO6, p a A 3 by 5 repeated measures ANOVA for the BAFVR for HUT 2a. HUT 2b. and HUT 2c vs. HüTl revealed the following: a significant main effect of expecimental schedule F(4,64) ~6.469, p ] r a significant effect For tilt position (time after HDT) F(2.64) =30.927, p d.0011 r no signi ficant 2-way interaction of experirnental schedule and tilt position p(8.64) d.352, p d r Scheffe's pst-hoc test revealed a si gni ficant diffennce between ( 1 ) Unprotected and PsDTr (@.O 190) and (2) Unprotected and PhUR (pc ). No other differences were detected. An examination of Figure 5-12 illustrates that FVR decreased at HDT and HUT2a then recovered during HUnbc. FVR demased more at HUV-a-c for the G-suit inflation mns versus Unprotected. PhUR had increased 96- vdues during when compared to al1 other expenmentd schedules.

108 Figure 5-12 Percent change in FVR Mean i: SEM mt position Unprolrctcd: No inflation. Iimn of prc muid past unprotcctcd mm: PaM% Pressure mrml. inflation During Transition ro HUTZ: PsDTc Pressure normal. slow inflation During Transition to HUTZ; PnUR: Rcssum noml. inflation Upon khing HUTZ; PhUR: Rcssurc high, infiaiion Upon bching Hm Sutisücai dcnoîailon: * aemw HURs-e: Unpmtcncd n. RiYi?. Unpmiencd vs. PbUR

109 6.0 Discussion 6.1 Roiteration of experimental objectives As stated previously. the physiologicai effects of +Gz, the measures developed to countenct these effects, and the protection afforded by this equipment have been studied thoroughly since World War Ii. However, there has ken little investigation into the cardiovascular response to the PPEM or the effectiveness of the countermeasures used to protect against the PPE. The purpose of this study was to use a low-intensity tilt table mode1 of the PPEM while intervening with various G-suit inflation schedules in order to: (1) Provide insight into the cardiovascular response to the PPEM. (1) Improve the understanding of the effect of various G-suit inflation schedules on protection against the PPEM. Therefore, examining if: -(i) G-suit inflation ameliorates the hypotensive response during the PPEM. -(ii) varying the timing of G-suit inflation further ameliorates the hypotensive response during the PPEM. -(iii) varying the pressure of G-suit inflation further ameliorates the h ypotensive response during the PPEM

110 (3) Aid in the production of an electronic 'smart' G-valve that could deliver G-suit inflation with the timing and pressure schedule necessary for optimal protection during the PPEM- Considenng these three main objectives, the following discussion will examine what was elucidated by the present study. 6.2 Major findings (1) G-suit inflation ameliorated the hypotensive response to the PPEM. (2) The results were not conclusive whether varying the timing or pressure of G-suit inflation further ameliorated hypotensive response to the PPEM. 6.3 Insight into the crvdiovascuiar response to the PPEM As stated previously, the carotid barorecepton are part of a neurological mechanism which conirols BP transient fluctuations. This baroreceptor-mediated reflex (or baroreflex) acts to minimize changes in HLBP and maintain cecebral perhision under varying hydrostatic forces. This includes the h ydrostatic changes resulting for gravi toinertial forces such as positive and negative Gz. It has been found that when a pilot experiences -Gz direcily before ffiz G- tolerance is diminished [1,19.3 1,36,39,41]. This reduction a G-tolerance has been

111 attributed to an increase in parasympathetic activity associated with camtid baroreceptor stimulation, resulting in bradycardia, decreased cudiac contractility, and peripheral vasodilation in order to minimize increases in HLBP [L, 21,38,57]. Since the demands of +Gz exposure require tachycardia, increased SV, and vasoconstriction to maintain HLBP, a pilot may be "physiologically biased against +Gz tolerance following -Gz exposure [38]. This decreased G-tolemce phenomenon is known as the PPE [2]. The majonty of this push-pull research has been perfonned using unprotected subjects [1, 8, 19,71,31, ,39.41]. Therefore, insight into the cardiovascular response to the PPEM can be gamered through the examination of the unprotected schedule and a cornparison of these findings to previous research Cardiovascular effeets of HDT for the unprotected schedule For the unprotected schedule, G-transition from HUT to HDT resulted in the inversion of the hydrostatic column and the translocation of blood from the lower vasculature to the torso and head. This increase in central blood volume (CBV) is supported by a decrease in Zo values (Figure 5-7). Heart-level SBP and MAP for the unprotected schedule were relatively unchanged by the increase in CBV. As illustrated in Figure 5-3 and 5-4, SBP and MAP were found to decrease 3 and 6% respective[ y (Note- al1 percent change values for this section cm be observed in Appendix C). These values are similar to those of the HUTl position due to the close proximity of the heart to the hydmstatic indiffemce point [13]. However, SBP values at head-level. king relatively

112 much further from this point, were found to increase dramatically. As illustrated in Figure 5-5, the inversion of the hydrostatic column resulted in a 30% increase HLBP from pretilt for the unprotected condition. These results arp sirnilar to those found by previous studies [l, 2,7,21, ,58]. Goodman and LeSage [21,58] simulated the PPEM using rapid tilting (4S0/sec) from +lso HUT to 135" HDT to +lso HUT. in the HDT position, SBP and MAP were found to decrease 2% and 9% respectively while HLBP increased 31% [58]. Wilkins et al. [7] also found BP to be altered by G-transition. When subjects were tilted from 75' HUT to 75' HDT. BP measured imrnediately pst-transition from either the femoral or brachial artery was found to decrease slightly. Similar decreases in blood pressun have ben reported using other -Gz acceleration techniques. Centrifuge studies by Ryan [6] and Lehr [l, 191 have reported SBP decreases during -Gz. Banks [2.39] has also observed BP demases under -Gz using the conolis accelention platform and Prior [ 1,311, w hile exposing subjects to 30 seconds of -Gz flight, also noted a decrease in SBP and MAP. These decreases in BP are the result of baroreflex-mediated BP control mechanisms. Increased CBV dunng -Gz nsults in an increase in venous retum and an increase in carotid transmural pressure (381. This stimulates the aortic and carotid baroreceptors. resulting in reflex cardiovascular changes in an attempt to rninimize increases in HLBP. These reflex alterations can be obsetved through the examination of the min determinants of BP; HR, SV, CO, and TPR. Since it is a main determinant of BP, HR would be expected to ciecrease under - Gz conditions in order to minimize inmases in HLBP. The HR results of the pcesent

113 study support ihis notion. As illustrated in Figure 5-6, HR decreased approximately 17% during HDT for the unprotected schedule. Similar findings for Gz simulations has been reported in other studies [6,7.2 1,38,44-46,58 ]. Ryan et ai. [6], w hen tilting subjects rom 60" HUT to 60' HOT. found an abrupt slowing of HR from 95 bats per minute (bpm) to 65 bpm. This is the equivalent of a 32% relative decrease in HR. This bnidycudic response is sirnilar in direction yet larger in magnitude than the response seen in our simulation possibly the result of a longer (1 minute) HDT period and an increased (60' HDT) tilt angle. HUT to HDT transitions performed by Green [44] and Fletcher [45] have also yielded HR results comparable to the present study. Both investigators insinuated that the observed bradycardic response was due to a reflex mechanism. Evidence of this baroreflex-mediated BP regulation system was provided by Abel [46]. Abel monitored the HR. BP, and carotid blood flow of anesthetized dogs in the HUT, horizontal, and HDT position. Carotid blood flow and MAP were found to increase during HDT resulting in profound bradycardia. After the dogs were denervated to block the effect of this baroreflex arc, the animals' ability to compensate for Hü'ï and HDT induced BP changes was greatly impaired During the HDT denervation mns, carotid blood flow and BP increased yet HR remained unchanged. Although performed on animals, this suggests the importance of the HR baroreflex response as a human compensatory mec hanism for G-transitions. An in-flight study by Banks et al. [38] also yielded a bradycardic response during -GE exposures. Banks exposed pilots to 15 seconds of -1 Oz, which was preceded and followed by 5 minutes of +L Gz level flight. A marked decline in HR wns reported during

114 -Gz. Banks ûttributed this bradycardia to a -Gz initiated shift in blood volume resulting in carotid transmural pressure changes and baroreceptor stimulation. Banks believed that this stimulation caused a increased parasympathetic acti vity, decreasing HR but also causing peripheral vasodilation and demased cardiac contractility. This was recognized as a potential hazard during increase +Gz flight where tachycardia. elevated CO. and vasoconstriction are necessary to tolerite increased +Gz stress. Centrifuge studies have also noted a decrease in HR during -Gz exposure [L. 61. Lehr and Pnor [l, 191 subjected individuals to 30 seconds of -Gz exposure dunng a centrifuge simulation of the PPEM. The investigators found a "suiking bndycardia" during -Gz and heart-level BP, was also found to progressively decrease throughout the 30 second exposure. Prior attributed these cardiovascular changes to peripheral vasodilation and altered CO under Gz, although these parameten were not rneasured. Evidence of decnased vascular resistance under -Gz conditions speculated by previous investigations [l was pmvided by Goodman and LeSage [21.58]. When simulnting the PPEM using the tilt table, Goodman found significant changes in TPR. FBF, and FVR. In the 45" HDT position, TPR and FVR were found to decrease 28% and 68% respectively while FBF increased an estimated 109% [58]. Goodman suggested that these changes were a caused by vasodilation and sympathetic withdrawal envoked by HDT. The present study supports Goodman's results. As iltustrated in Figures 5-10 to 5-12, during HDT, TPRi decreased 248, FVR decreased 19%, and FBF increased 49% cornpared to pre-tilt values. Although these results are not of the same magnitude as Goodman's study. they still suggest the presence of barorek-mediated BP control through decreased vascdar tone.

115 During unprotected HDT, it would seem logical that in order to attempt to minimize increases in HLBP, the barorefiex would act to decrease SV and CO. However, SI and CI were found to increase dunng HDT 53% and 24% respectively. Previous tilt studies by Goodman [21] and Wilkins (71 have also reported these SV and CO incnases in the HDT position. The incrrase in SI and CI values during HDT is the result of the inversion of the hydrostatic column. Dunng -Gz. the medulla, responding to camtid baroreceptor afferents, acts to cause parasympathetic activity in an attempt to decresse myocardial contraction and CO. However, the translocation of blood initiated by HDT causes a significant. passive inmase in venous retum and increased right atnal pressure. This leads to increased venincular load and ejection via the Frank-Starling mechanism [59]. This competing influence results in the observed inmases in SI and CI. In sum. the HDT position caused an increase in CBV resulting in increased cuotid transmua1 pressure. The resultant stimulation of the cûrotid baroreceptors led to profound bradycardia and decreased penpheral vascular resistance in an attempt to maintain HLBP. These results are comparable to previous findings for unprotected -Gz simulations The diovascuhr effats of subsequent BUT during unprotected mm Dunng subsequent HUT m) for the unprotected schedule. SBP, MAP, and HLBP were al1 found to significantly decrease. As illustrated in Figure 5-1. the

116 LOS immediate decrease in SBP (de) was 26% for the unprotected schedule versus pre-tilt values. Figure , and 5-5 depict decreases in SBP, MAP, and HLBP of 16% and 19% respectively during HUna (3 to 10 seconds after the beginning of subsequent HUT). Figure 5-2 shows SBP took approximately 18 seconds to recover to 90% of pre-tilt values. This is supported by SBP and MAP results which are almost fully recovered by HUT2b (15 to 22 seconds after the beginning of subsequent HüT). These results are sirnilar to previous PPEM studies [1,21.3 1,38,39,58,60]. For instance. using a conolis acceleration platform, Banks subjected volunteers to varying magnitudes of -Gz before Gz exposure [38,39]. Systolic, diastolic, and pulse pressure were al1 shown to significantly decrease dunng +Gz exposure. Increasing the duration and magnitude of -Gz was found to yield greater declines for ail BP measurements. SBP was reported to recover within approximately 15 seconds for most schedules. The effect of the PPEM upon BP has also been demonstrated in-flight by Prior [311. Using Hunter T-7 aircraft. Prior recorded subject MAP during +4 Gz acceleration when preceded by either +L Gz or -2.5 Gz flight. Immediately after subsequent +Gz exposure, MAP was found to be 58% less for the -2.5 Gz schedule versus the +l Gz schedule. This ciifference still existed 6 seconds after the initiation of +4 Gz. These results are similar to those of the present study in that they show a decrease in MAP dunng subsequent +Gz exposure. However, the increased G-envelope of the aidt compand to the tilt table results in greater declines in BP. Using a lso HUT to 13S0 HDT to 15' HUT tilt table simulation of the PPEM, Goodman and LeSage found SBP and MAP to demase 14% and 19% respectively after

117 3 to 10 seconds of subsequent HUT [58]. Over the same time period, HLBP decreased 16% compmd to pre-tilt values. Recovery for al1 BP parameten occurred after approximately 18 seconds after the initiation of subsequent HUT. As explained previously, it is believed that the bradycardia and decreased vascular tone associated with -Gz inhibits the body's ability to respond to +Gz exposure leading to inhibi ted BP ncovery and PPE symptoms [l, 2, ,601. However, little research has been performed to investigate the effect of negative to positive G-transitions on HR and vascular response. A study by Fletcher et ai revealed a systematic relationship between HR and G exposure. Using a tilt table to place subjects in HLTT and HDT positions in multiples of 45" from horizontal, HR was found to be highest in the vertical HUT position and lowest in the vertical HDT position. More irnportantly, the cardio-deceleration pmcess was reported to be accomplished within 2 to 3 seconds while cardio-acceleration required up to 20 seconds for completion. Since tachycardia is a slower process than bradycardia, this provides evidence that negative to positive G transition could lead to delays in BP recovery dunng subseqwnt +Gz exposuns of the PPEM. An in-flight study by Banks et al. [38] also reported a duraiion difference between bradycardic and tachycmiic response. Banks fond cardio-deceleration was completed within 2 to 2.5 seconds of the initiation of -Gz exposure. However. completion of cardioacceleration during subsequent +Gz exposure requind 4 to 6 seconds. Banks believed that this delay in tachycardie response was a potentiai problem during G-transition. Again, since cardia-acceleration is a slower process than catdio-deceleration, the body's ability to cope with +Gz would be impaind after -Gz exposure.

118 As illustrated in Figure 5-6, the results of the present study found HR for the unprotected schedule to increase 9% above pre-tilt values at HUT2a (3 to 10 seconds after reaching subsequent HUT). HR returned toward resting levels by HUnb (15-22 seconds afier reaching subsequent HUT). Since HR values were not exarnined until seconds into the HDT position, a cornparison between immediate bradycardic and tiichycardic response cm not be made. However, the rate of cardio-accelention under +Gz exposure observed for the present study appears to coincide with the results of Fletcher [45] and Banks [38]. Therefore. the delayed time course of tachycardie versus bradycardic response remains a possible determinant for the delay in BP recovery dunng the PPEM. Numerous studies have suggested a delay in vasoconstriction as a possible explanation for delayed BP recovery during the PPEM [21,38, However, little research has actually quantified the vasomotor response dunng G-transi tion. Bath et al. [61] have illustrated the rate of vasornotor response is slow when the body attempts to control BP. Bath used a neck suction cuff to examine the cardiovascular response to cmtid baroreceptor stimulation. Neck suction caused increased carotid transmural pressure and, therefore. carotid stimulation. Suction caused demased sympathetic activity resulting in a decrease in HR and vasodilation in order to decrease BP. However, Bath noted that the main rate limiting factor for blood pressure nsponsiveness was the peripheral vascular beds since their reaction to aitered baroreceptor stimulation was "sluggish". Doe et al. [4û] used dogs to investigate the magnitude and time course of baroreceptor-mediated vascular response. Doe constnicted a perfusion circuit which

119 allowed for independent perfusion pressure and flow control of the aorta and the carotid sinus. By keeping subdiaphramatic pressure constant and altering carotid perfusion pressure, Doe was able to determine the effect of altered carotid baroreceptor activity on vascular resistance. Doe found that the time to reach 75% of the maximum dilator response was significantly shorter than the comsponding constrictor response. Therefore, carotid biiroreceptor-mediated vasodilation occurs more rapidly than vasoconstriction. As explained previously, maneuvers such as -Gz acceleration that cause expeditious changes in carotid bamreceptor pressure may reduce vascular resistance response. Thus, when -Gz precedes +Gz, Doe predicted larger decreases in BP due to impaired vasomotor response. This delay in vasomotor response has been reported dunng the PPEM. Using a tilt table. Goodman and LeSage [21,58] found TPR to be greater during subsequent HUT than the 45' HDT position. However, subsequent HUT TPR values were stili348 below those measured pre-tilt [58]. TPR did increase thmughout subsequent +Gz exposure, however, full recovery did not occur until approximately 33 seconds after the initiation of HUT. Since simulations measunng vasoconstriction under +Gz-only conditions show vasoconstriction is initiated within 7 to 10 seconds (341, Goodman's findings provide evidence that previous -Gz exposure results in a delay in vasomotor response. The results of the present study are sirnilm to Goodman. As illusrraied in Figure 5-10, TPRi values are decreased 40% dunng HUT2a. Evidence of increased TPR was no< observed until HUT2b ( seconds after initiation of HUT) and full recovery was still not achieved at HUT2c, nearly 35 seconds after HUT. FVR and FBF results depicted in Figure 5-11 and 5-12 also provide evidence of delayed vasoconsuiction. Dunng HUTI!a, FVR remained 19% below and FBF 41 % above pre-tilt values. These values also did not

120 show signs of recovery until HUT2b. Sirnilar FVR and FBF values have been reported by Goodman and LeSage [58]. All of these studies lend support to speculation that sympathetic response to ffiz exposure is delayed when preceded by -Gz. Sympathetic drive acts to control vascular tone. If -Gz exposure delays sympathetic response during +Gz. vasoconstriction will be delayed and the maintenance of HLBP will be adversely effected. nius, delayed vasoconstriction as a result of delayed sympathetic drive may be detrimental to G- tolennce and. therefore, may be a possible explmation to the cause of the PPE. It should be noted that during subsequent HUT, SI and CI were found to decrease back towards resting values for the unprotected schedule. Again this observed decrease in SI wd CI occurred via the Frank-Starling mechanism. As illustrated by Zo values in Figure 5-7. blood which was translocated to the torso during HDT is shifted back towards the lower vasculature. The passive decrease in venous return which coincides with this shift results in decreased right ahial pressure and left ventricular unloading. Therefore, as depicted in Figure 5-8 and 5-9, SI and CI values are reduced during subsequent HUT. In sum, for the unprotected runs, the results of the cardiovascular responses to the PPEM were not atypical when compared to other push-pull studies. HDT caused bradycardia and decreased vascular tesistance in an attempt to maintain HLBP. Dunng subsequent HUT. there was evidence of a delay in the initiation of cardio-acceleration and vasoconstriction. This was believed to be the result of a delayed sympathetic cirive caused by -Gz exposure pnor to subsequent ffiz. This delay is believed to adversely effect the time course of BP recovery and has been implicated as a sipificant cause of the PPE.

121 6.4 The effect of G-suit inflation upon the physiologie responses to the PPEM The acute effects of C-suit inflation The protection effect of the G-suit against the PPEM can be investigated through the examination of the immediate cardiovascular response to G-suit inflation. In the present study, this can be ascertained through the examination of HUT2a data, collected 3 to 10 seconds after the commencement of subsequent +Gz exposure. At HUna, al1 of the protection schedules were found to have a significant effect on the measured BP parameters. As illustrated in Figures , and 5-5. G-suit inflation resulted in an approximate 11-13% increase in SBP, 1420% increase in MAP. and a 13-16% increase in HLBP venus the unprotected schedule. This minimization of initial BP decreases was expected based upon results of pemous +Gz protection studies. For instance. when investigating the effect of G-suit inflation on BP changes produced by the human centrifuge, Wood et al. [62] found that without G-suit inflation, SBP demased 3 mmhg per unit of G. However, with G-suit inflation, SBP was reported to increase 5 mmhg per unit of G. Sirnilar results were found by Gray et al. [49] while exarnining the effects of G-suit inflation at 60' HUT. When the G-suit was inflated to 80

122 mmhg, SBP and MAP, recorded via catheterization of the brachial artery, were found to increase 18% and 7% respectively venus control. Although these results were reported without previous -Gz exposure. they lend support to our findings in that the G-suit minimized increases in BP during subsequent +Gz conditions. Based on what is known from earlier research [22,23,32,34,49,62], G-suit inflation is proposed to increase SBP cornpared to the unprotected schedule through three modes of action. First, G-suit inflation increases CBV therefore supporting venous retum. This wouid support SV and CO via the Frank-SiarIing mechanism, thus increasing BP for protected versus unprotected schedules. Second, the G-suit acts to raise the diaphmgm. This elevates the hem, therefore, minimizing increases in the hem-to-brain hydrostatic column dunng G-stress. Thirdly, G-suit inflation is believed to increase periphenl vascular resistance. Since TPR is a main detenninant of BP. increases in TPR initiated by G-suit inflation would assist in the increase in SBP values compared to unproiected schedules. However. our findings do not coincide with these proposed mechanisms. As illustrated in Figure 5-7, decreased Zo values for the protection schedules suggest an increase in CBV. Based on previous studies, this increase in CBV should have tnnslated to inmased SV and CO values. Gray et al. [49] found that G-suit inflation in the 60" HüT position resulted in an immediate 53% increase in CI which was attributed to a 42% increase in CBV. A study of G-suit inflation in the +l Gz environment by Seaworih et al found 2 psi inflations in the upright position increased SV and CO 40% and 37% respectively. As illustrated in Figure 5-8 and 5-9. these findings are not similar to our results. No significant differences existed between SI or CI values for the protected versus unprotected schedules.

123 As for the mode of action of peripheral vascular resistance. Figure 5-10 shows that G-suit inflation appears to immediately elevate TPR. However, only one G-suit schedule, nomai pressure with inflation upon reaching subsequent HUT (hur), was found to be significantly different hm the unprotected schedule. Also, if TPR was increased by G-suit inflation. FVR values should increase and FBF values should decrease for the protected versus unprotected schedules. However, as illustrated in the HUT2a position in Figure and 5-12, this does not occur immediately upon G-suit inflation, As illustrated above, SV, CO, and vascular resistance results ;ue not what would be expected based on previous literature. These disc~pancies are most likely neurological in origin possibly arising from confiicting afferent messages from the carotid and cardio- pulrnonary barorecepton. The theory of conflicting afferents has been postulated by Wood [63] who proposed that G-suit inflation under +Gz stress caused the depressor reflex of the aortic m h to go unopposed by the pressor reflex of the carotid sinus. Wood believed that various acute cardiovascular complications, including cardiac arrhythmias, could arise from this conflict. Bath et al. [61], while investigating the effects of neck suction on cardiovascular activity, also discussed the effects of conflicting information from different baroreceptor "stationst'. During neck suction, carotid transmural pressure was altered therefore stimulating the carotid baroreceptors. However, other arteriai barorecepton, including those of the aoriic arch. remained unstimulated. As a result, Bath noted changes in BP which could not be explained by carotid stimulation alone.

124 Shi et al discussed the possibility of the attenuation of the carotid barorenex by input fmm other artenal baroreceptors. Shi used neck suction and pressure to stimulate the carotid baroreceptors while using lower body positive pressure (LBPP) to increase CBV and stimulate the baroreceptors of the aortic arch. Shi found that the increase in CBV diminished carotid baroreflex control of cardiac and vasomotor function. During subsequent HUT for the present investigation. the cmtid barorecepton would be unloaded due to the blood shift caused by ffiz exposure. However, as seen in Figure 5-7, G-suit inflation caused a decrease in Zo values venus the unprotected schedule. Therefore. CBV was increased by G-suit inflation possibly stimulating aortic arch baroreceptors. According to the theory confiicting afferents and the results of Shi [64], this could have resulted in the attenuation of the carotid baroreflex response. This is a possible explanation for the Iack of significant changes observed for SI. CI. and peripheral resistance values during G-suit inflation. Another potential cause of the significant changes in BP and the lack of significant changes in other cardiovascular parameters resulting from G-suit inflation is the possible influence of muscle pressure receptors. Numerous studies have suggested that afferent messages arising from muscle pressure receptor stimulation cm effect cardiovascular baroreflex response ( Using decerebnte cats. Kumada et al. [65] demonsmed the effect of sciatic nerve stimulation (SNS) upon the carotid sinus baroreflex. When intm-carotid sinus pressure was increased. HR. CO and TPR decreased in an attempt to lower BP. However, when intracarotid sinus pressure increases were coupled with SNS, the reflex control of HR. CO, and TPR was attenuated. Since muscles in the lower extremities send afferents via

125 the sciatic nerve, this suggests that affe~nts resulting from the excitation of muscle receptors. perhaps by pressure caused by G-suit inflation, may inhibit the carotid baroreflex response. Further evidence supporting Kumada's results was provided by McWilliam and Yang [66]. Again using decerebrate cats, McWilliam and Yang found that stimulation of group III and IV muscle afferents led io a decreie in the prolongation of the R-R intervai during increases in intm-camtid sinus pressure. Since the nerves stimulated in the McWilliam study innervate skeletal muscle and have been found to alter the cardiovascular effects the carotid baroreceptor stimulation, this suggests a link between muscle tissue and the carotid baroreflexes. Recent work on the cardiovascular effect of muscle pressure receptor stimulation has been perforrned using extemai pressure on muscle tissue. Using a pediatric blood pressure cuff, Stebbins et al. [68] placed extemal pressure upon the triceps surae of the adult cat. This resulted in a slight inmase in MAP but had no effect upon HR. A study by Shi et al. [67] exposed human subjects to graded LBPP. It was discovered that LBPP of 20 torr caused significant increases in MAP, SV, and CO. LBPP pater than 20 torr led to inmases in MAP and FBF, however, HR, FVR, and TPR values were unaltered from rest and no further inmases in SV and CO were observed. Shi suggested that these sup pressed vascular nsistance and bradycardia reflex msponses were possi bl y caused b y the activation of muscle pressure receptots. It is implied that afferents h m these pressure receptors in response to LBPP aitered the baroreceptor response to BP changes, attenuating the expected HR, FVR, TPR, SV, and CO changes.

126 The conclusions of these studies may explain the significant increases in BP yet lack of significant SI, CI. TPR, FBF. and FVR findings of the present investigation. The G-suit placed significant pressure upon the muscles of the lower extremities and the abdomen. Therefore, although the G-suit inflation increased CBV and BP, it also could have stimulated muscle pressure recepton whose afferents may attenuate the typical barorefiex ~sponsc. In sum. G-suit inflation did have an acute effect upon BP as suggested frorn significant elevations in SBP. MAP, and HLBP for al1 protected versus unprotected schedules in the HUT2a position. Since the maintenance of SBP and HLBP within the fint few seconds of ffiz-exposure is criticai in the amelioration of the PPE, these rrsults suggest that G-suit inflation is an adequate method of protection during low-intensity PPEMs The effect of G-suit inflation over time The cardiovascular response rate to G-suit inflation can be determined through the examination of BP parameters over time. As illustrated in Figure 5-3,s-4, and 5-5, SBP, MAP, and HLBP ciifferences between protected and unprotected schedules wen reduced across HUT2a (3-10 seconds after initiation of HüT) to HUT2c (27-35 seconds after initiation of HUT). This reduction was most likely caused by cardiovascular adaptation to +Gz stress. Using a tilt table PPEM simulation similar to the present study, Goodman and Lesage [58] found the cardiovascular reflexes, unaided by G-suit inflation, reacted to

127 recover SBP within approximately seconds hm the initiation of HUT. Figure 5-2 illustrates that SBP recovery for the unprotected schedule of the present study was similar to Goodman's findings. requinng approximately 17 seconds to ntum to near pre-tilt values. Therefore. although G-suit inflation caused an acute increase in SBP values compared to the unprotected schedule, schedule differences were reduced over time due to unassisted cardiovascular adaptation. This reduction in the difference between protected and unpmtected schedules over time is aiso observed for other cardiovascular panmeters. For instance, as Figures 5-5 and 5-10 show. HR and TPRi values for dl schedules appear quite similar as lwt2b and HUT2c are reached. Since tachycardia and vasoconstriction are the main reflex defenses against ffiz exposure, it can ôe postulated that by the time HUTZb (15-12 seconds after the initiation of HUT) is reached, the delay in the barorefiex response caused by the PPEM has been overcome. As with HUT2a data. CI results appear to be quite variable for al1 schedules across HUT2a-c. Again, CI variability could also be the result of conflicting efferent theory postuiated in the previous section. As illustrated in Figure 5-7. Zo values remain decreased by G-suit inflation dunng HUT2a-c, thus CBV is maintained. Therefore, the baroreceptors of the aortic arch are stimulated while the carotid baroreceptors have been unloaded by the ffiz stress. If the carotid and cardiac baroreceptors are sending diffe~nt inputs to the medulla it could result in confliciing efferents king sent to the endsrgans. This could cause variations in cardiovascular parameters such as HR, SV, and TPRi. Since HR, SV. and TPRi are the main detenninants of CO, CI vdues across HUT2a-c could be effected.

128 Again, it is also possible that lack of significance in cardiovascular parameters over time is the result of muscle pressure receptor influence [64-68). Just as with the acute effects of inflation, prolonged G-suit inflation may stimulate muscle pressure receptors which attenuate cardiovascular response to baroreceptor stimulation. This could effect cardiovascular response results leading to diminished differences between protected and unprotected schedules over time. In sum, G-suit inflation did have an effect both immediately upon reaching subsequent HUT (HUTla) and over time (HUT2a-c) resulting in the maintenance of SBP. MAP, and HLBP. The differences between protection and unprotected schedules was observed to diminish over time due, most likely, to the adaptation of the cardiovascular system. Again. since the maintenance of BP within the fint few seconds of +Gz-exposure is critical in the iunelioration of the PPE, these results suggest that G-suit inflation is an adequate protective mesure dunng low-intensity PPEMs The effoct of varying the timing and proswrr of G-suit inflation As illustrated in the discussion above, significant differences existed between G- suit and unprotected schedules. However, very few significant differences were found between the various G-suit schedules. This was most likely the result of high G-suit pressures paired with the limited Gtnvelope of the tilt table. Operationally, G-suit inflation is initiated at +2 Gz with pressure king aven at a rate of 1.5 psi per G to a maximum of 10 psi [23]. In the present snidy, G-suit inflation

129 occurred during +L Gz or less and pressure was given at either 2 or 3 psi. The tilt table, although it provides enough stimulation to provoke the symptoms of the PPE, may not produce the magnitude of.g necessary to determine differences between protection schedules. G-suit schedules of such high pressure may requin higher +Gz conditions in order to assess w hether clifferences in protection effects. Nonetheless, although not significantly different frorn each other, there were cenain instances in which certain G-suit schedules differed in their significance with the unprotected schedule. The most noteworthy differences between protection and unprotected schedules were observed for the immediate decrease in SBP (dp) and the rate of SBP recovery (dt) dunng subseqwnt Hm. Since the recovery of head-level SBP is of utmost importance to tolerance of the PPE, these differences are in need of investigation. As dp results fmm Figure 5-1 illustrate, SBP decreased less for al1 protection schedules compared to the unprotected schedule. However, these reductions were only found to be significant for the normal pressure (2 psi) and slow onset inflations initiated during transition to subsequent HUT (RiDTr and PsDTr, respectively). The normal pressure inflation schedule initiated upon naching subsequent HUT (PnUR) was also statistically significant in reducing dp but this findings must be considerrd tentatively since its p-vdue was where 0.05 is the level of significance. Inflation upon reaching subsequent HUT may be too late in the tilt maneuver to prevent an irnmediate drop in SBP. Inflations initiated during transition act to maintain CBV and, therefore, maintain SBP even before subsequent HUT is reached. Zo values for the fwï2a do not necessarily support this notion since the only significantly difference observed for Zo was between the PnDTr and PhUR (high pressure upon reaching

130 subsequent HUT) schedules. However, it must be noted that HUT2a data was collected 3-10 seconds after the subsequent HUT was reached whereas dp data was collected irnmediately upon reaching subsequent HUT. Thus. Zo values may not have been recorded early enough to detect differences between protection schedules. Regardless, since the maintenance of SBP within the first few seconds of ffiz exposure is critical to G-tolennce, inflation initiated during transition xnay have a protection advantage over schedules initiated upon reaching HUT by preventing the immediate decrease in SBP. Time of SBP recovery (dt) results also yielded interesting differences between protection schedules. As iliustrated in Figure 5-3, the duntion of SBP recovery was foound to decrease for al1 G-suit schedules. However, only inflations initiated upon reaching HüT were significantly different than the unprotected schedule. It is somewhat surprising, that inflations initiated dunng transition did not reduce mean dt values significantly. The possibility exists that using a transition-based inflation schedule may provide G-suit inflation too enrly in the PPEM to be effective in reducing dt. Early G-suit inflation could interfen with the carotid depressor reflex under +Gr stress. While an increased initial CBV would assist in the maintenance of SBP (as supponed by significantly nduced dp for during transition inflations), the cardiopulmonary baroreceptor stimulation it provides could effectively inhibit the carotid depressor refiexes by blunting HR and vascular tone reactions even before subsequent HUT is reached (641. This is supponed by the non-significant reductions in BP recovery observed for the during transition runs. This could be the source of the lack of significant ciifference between dt results for during transition inflations versus the unprotected SC hedule.

131 These dp and dt results are in agreement with findings fiom an in-flight PPEM study by Rior et al. [311. Prior exposed subjects to either -2.5 Gz flight or +1 Gz flight directly pnor to a +4 Gz tum. These sequence were performed both with and without G- suit inflation coinciding with the beginning of az. Rior found that. compared to the +l Gz trials. MAP fell precipitously when -Gz preceded +Gz. This initial decrease in BP was unaided by G-suit inflation. however. inflation was found to speed the rate of BP recovery. Although no inflations were perfonned dunng transition to subsequent +Gz, these results are similar to our results for inflations performed upon reaching HUT. Other significant differences were found for FBF and FVR data across the HUT2a-c positions. As show by Figure and the PhUR schedule was observed to have higher FBF and lower FVR values compared to the other experimental schedules. This suggests that the mechanical effect of increased G-suit pressure was responsible for these FBF and FVR values. It is possible that the observed FBF and FVR changes for the PhUR schedule are the result of increased cenual venous pressure (CVP). FBF measurements were acquired using the technique of venous occlusion plethysmography. Occlusion was achieved through inflating a blood pressure cuff around the upper right arm to 50 mrnhg. Thus, if venous pressure is incnased above 50 mmhg, it could result in increased FBF values. Although it was not measured in the present study, Gray et al. [49] have shown CVP is increased by G-suit inflation in the +I Oz environment. This elevation in CVP could have resulted in increased FBF and decreased FVR values for the protection schedules versus the unprotected schedule. These differences would be even further exaggerated for the higher pressure and. therefore, higher CVP provided by the PhUR sdiedule.

132 In summary, it was difficult to determine if differences existed between the various G-suit timing and pressure schedules. Very few statistically significant differences were observed between &e protection schedules. However, this lack of statistical difference was most likely a function of inappropriately excessive G-suit pressure for a +1 Gz environment. despite pnceding -Gz exposure. That king said, differences between dp and dt results for G-suit schedules versus the unprotected schedule mises the possibly that certain protection schedules may have advantages with respect to defense against the PPE. Further investigation using higher +Gz conditions and operationail y correct inflation rates for those conditions is necessary if this assumption is indeed valid. 6.5 Conclusions Implications for opcmtions, future research, and the development of an optimal protection system and schedule versus the PPE The outcome of the present study is quite cleu. The tilt table simulation of the push-pull effect maneuver nmains a satisfactory method for examining the push-pull effect. However, while the tilt table simulation of the PPEM can illustrate effectiveness of G-suit inflation as a method of protection against the PPE the G-stimulus provided by the tilt table is tw weak to discover if differences between various G-suit schedules exists. Thus, in the firture. insight into the effectiveness of varîous timing and pressure

133 schedules used to counteract the PPE may be best left to multi-axeled centrifuges and inflight research. The increased Genvelopes of these research methods paired wi th the proper G-suit pressure for the higher magnitudes of G that they provide are most likely the best route to determining the most effective protection scheduk and system necessary to counteract the PPE Conchsions bused upon nul1 hypotheses (1) G-suit inflation ameliorated the hypotensive response to the PPEM (2) The results of the present study were not conclusive as to whether G-suit inflations of cenain timing or pressure will further meliorate hypotensive mponse to the PPEM. An increased G-envelope paired with opentionally proper G-suit inflation pressures for this G-stress are suggested for future investigations.

134 7.0 Limitations The experimental design for present study was found to have some limitations. These included: (1) Due to a fixed profile selection. investigators and subjects were not blind to the pressure and timing of G-suit inflation for each run. Thus, the possibility exists for experimenter and subject effect. However. this WGS minimized in part through generous rest periods between experimental runs. Since no differences were revealed between pre and post-unprotected schedules, there appem to be little possibility of order effect. (2) Another weaknesses in the experimental design was the addition of 'ready' G-suit prepressure. The G-suit was pressurized to approximaiely 0.3 psi for al1 G-suit schedules prior to the initiation of inflation. This was done in order CO minimize the lag in G-suit inflation during subsequent HüT. Although this pressure was minimal, it was pnsent for dl G-suit mns. Therefore, it may have hd a possible effect on experimental results. (3) The venous occlusion plethysmognphy technique for fonamr blood flow measurements also had limitations. Forearm venous occlusion was provided by a blood piessure cuff inflated to 50 mmhg around the upper right am. G-suit inflation may have

135 elevated venous pressure above 50 mmhg. As a result FBF values during G-suit inflation may have been over or underestimated. (4) There is also a possibility of impedance csrdiography calculûtion erron due to variations in respiration. Inspirations and expirations effect the dzldt values used to detennine SI and CI. However, it is assumed that the respiratory cycles of individuai subjects do not coincide. Therefore, variations due to respiration will be averaged in the measunments and will be negligible. (5) As stated previously, the tilt able has a limited G-envelope. The DClEM tilt table only reach to 135 degrees HDT and upright HUT resulting in a maximum change of to +L Gz, This. paired with a rotational speed of 45 degrees per second, provides much Iess G-stress than the aircraft or multi-axeled centrifuge. The tilt table still provides enough stimulation to provoke the cardiovascular changes involved in the PPE and can be used to illustrate the protective effect of G-suit inflation. however, it does not provide the stimulation necessary to examine diffennces between various G-suit inflation schedules. (6) Subjects may have ken anxious before the added stress G-suit inflations. As a result, they my have strained during runs involving G-suit inflation especially high pressure (PhUR) nins. Sfraining is a potmtial explanation for the statistical significance observed for SBP and HLBP at HDT for PhUR runs when no such significance should have existed. An EMG device could have been used to detemine if these speculated muscular contractions indeed ocçurred,

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141 46. Abel, FL., J.H.Pierce, and W.G. Guntheroth, Baroreceptor influence on postural changes in blood pressure and carotid bloodjzow. Amencan Journal of Physiology, (5): p Tuckman, J. and J. Shillingford, The Effects of Different Degrees of Tilt on Cardiac Output. Heurt Rate, and Blood Pressure in Normal Man. British Hem Journal, : p MacKenzie, C.G., R.J. Slaugther, and G.C. Knowlton, Slowing of the hean by inflation of the G-suit at 1 G,. 1945, RCAF Institute of Avaition Medicine: Toronto. 49. Gray. S., et al., Anite and Prolonged Eficts of G Suit Inflation on Cardiovascular Dynamics. Aerospace Medicine (1): p Pecaric, M., F. Buick, and J. Maloan. Cardiovascular responses associated with improved or delayed G-valve responsiveness. in 68th Annual Aerospace Medical Association Scientijic Meeting Hyatt Regency, Chicago. L Wesseling, K.H., A century of noninvasive artenal pressure measurenrent: from Marey to Penaz and Finapres. Homeostatsis, X(2-3): p Mol hw k, P.G.. a al., Initiai results of noninvasive measurement ofjbger blood pressure uccording to Pena Automedica, : p Gradwe l 1, DI., Validation of a nethod of continuous non-invasive monitoring of blood pressure during positive pressure breath ing in man. J. Ph y siol., : p. 170P. 54. Kubicek, W.G., et al., Datelopment and evaliiation of an impedmce cardiac output system. Aerospace Medicine, 1966(December): p

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143 64. Shi, X., et al., Carotid barorefiex responsiveness to lower body positive pressureinduced increases in central venous pressure. Am. I. Physiology, : p. H9 18- H Kumada. M.. K. Nogarni, and K. Sagawa, Modtîlation of carotid sinus baroreceptor reflex by sciatic newe stimulation. Am. J. Physiol., p McWilliam, PN. and T. Yang. Inhibition of cardiac vagal component of barorefle-r by group 111 and N afferents. Am. J. Physiol., ): p. H730-H Shi, X., C.G. Cnndall, and P.B. Raven, Hemodynamic responses to graded lower body positive pressure. Am. J. Physiol : p. H69-H S te b bins. CL.. et al., Reflex effect of skeletal miîscle mechanoreceptor stimulation on the cardiovascularsystem. J. Appl. Physiol., (4): p Newman, D.G. and R. Callister, The non-invasive assessment of stroke volume and cardiac output by impedance cardiogruphy: a review. Aviat. S pace and Environ. Med (8): p Fox, EL., and D.K. Matthews, The Physiologictzl Basis of Physical Education and Athl&s. 3rd ed , Philadelphia. Pennsylvania: WB. Saunders.

144 Appendix A Sample Recordings

145

146

147

148

149 PhUR

150 Appendix B ANOVA Results

151 ANOUA Table for DeCrelse in SBP (dp) ~ubpct Expertmenrat s cneauie Experimental scneduio ' Subpct L OF Sum of Squares Mean SQuare F-V atue P-V riue Lamoaa Pow cr 8 a 32 r t t t7q OOI~ I i Çchrttm for becteire in SEP (dp) E!tett: Experim rntrl rchrdule Signiticance Leval: S K Unprotmcted. PnOTr MeIn OMf. Cl& OHf?-V 81~0 13.3' O071 1 S Ungrotrcted. PrOTr, 13.07s t i.o085 1 S Unproucted. PnUR Unprotecteb, PRUR PnOTr. PI OTr PnOTr, RiUR PnOTr. PhUR PsOtr. PnUR PsOTr. PhUR PnUR. PhUR 1 1 t f t O487 f S S Ï (,3999 ( t / I t t0.539(.9940i

152 ANOVA Table for Ttm r of S8P rmcovery (dt) Schette for Tim a of SEP recovery (dt) Utmct: Exprrimentrl schrduk Signitlcaitca Leuel: S?5 Unproieclad. PnOTr Unptotecna. PsOTr Unproacred, PnUR Unpratecred. PnUR PnOTr, Ps OTr PnOTr, PnUR PnOTr, UR PsOTr. P~UR PsOTr. PCiUU?NA. htjr Y Marn OU(. Cr& Out P-Vabr ) O OS50 ' ).OOIZ!S i.a006 j S ~ t i usa a t a723 j ,9993 '

153 ANOVA table for?b change in SBP rt HOT OF Sum of Sauares MeIn S~ulrh F-V alue P-V plue Lambda Pow er I ai t2oo.szo I t so.o.ra I I t I i Scheffe for?c chrngo in SBP it HDT EIfect: Exparlm m til s chadule Significince Level: 5 K Mem Diff. ait. Dif t P-V alue Unpratected. PnOTr Unproucted. PnUR -.O w Unpratacted. PhUR O496! S Unprotecwd, PsOTr t PnOTr. PnUR PnOTr, RUR PnOTr, hotr PnUR. PhUA PnUR, PsOTr PhUR, PsOTr

154 ANOVA Table tor K change in SBP at HUT28 Schettr for S change in SB? rt nln2r Ehct: Exprrim rntrl s chodule Signillclntr Lovei:l% Maan Oiff, Crit. Oiff P-Vaiue Unprotecied. PnUR Unprottctra, PsOTr PnOTr. WUR PnOTr. P~UR PnOTr. ROTr PnUR, PhUR PnUR PS DT~ y3.z O016 S 29 t 1 9,334 1 ~ PA& aa r t~ r ~s%Ï 4 5 t i /.999a 1

155 ANOVA Tablo tar?l change in S8P at HUTZn-c OF Sum ot Suuares Mean Square F-Vakr P-Vahe Lambda POW er r Subrct 8 I I! t 0 Expomenrat scneduu 4 : I om6 l ; -984 Etpelimenta~ scnrauu suowct 1 32' t ,559! I I I ~JL 1 f pasilbn i zi : tot r-243 i n.120 I coo01 : t s t.oao? I ~ i poswn ~ t Sublect I i I I 1 Gpermntal scnoaule ~osltion / I! ! 49.tft Ot59 I ).893 i a prritnontal scnoau~e ~ i posdlon ~ t SU., 1 64 I 122S.m i I I I! Schalta lor % changr in SBP at HUTPI-e Ettmct: Exparlmental schmduh Signlflcancm LavakS?C Mean Wt. CnLDdf PVake Unp rotectod. PnOTr Unproactma. WUR Unprotectma. RUR ( m 4 Unprotmed. ROtr t, S Schotto far?l change in S8P at HUTZa-c EItm ct: Tilt pas ition Signftlcanco frvet: J?b Mean Ollt. Cnt. O#f PValrr HUTZa. HUT2b nma. nunc HUTZb. HUfZc

156 ANOVA Table for Ue change in MAP at HOT Su blect Sprrimentai scneauy. Sirparimentri scheauu ' Suotect OF Sum at Sauares Mran Sauare F-V alua P-V alue tsrnaoa Paw ef J tr r 969 I 1 1 a a s ',0399 i t ', t 3 ' , Scheffe for?i change in MAP at HDT Ufect: Experimantal sctiedule Slgnificance Level: 5 K Un pro tec:eo,?notr Un pro tecred. PnUR Unprotectea. PhUU Unproticma, ROTr PnOTr. PnUR PnOTr. PhUR PnOTr, Ptotr PnUR. PhUU PnUR. Pr OTr?~IUR. Pr OTr Mean Oit f. Crit. Oüf P-v

157 ANOVA Table for Uo change in MAP at HUT2a OF Sum ot Sauatrs Mean S~uare S-V aiue P-V aiue Carnuaa PCW ar suujact Exparunenial sc!teduk Expermenial scneauk ' SuOpct 8 I t e.f ao d _ t I I 1 cqû i 000 l I I;icnene ;or Y" change in MAP at HUTZa Effect: Exparimental sciiedule Signiflcance Level: S % Unprotoctea. PnOTr -l &O t 0.050!.O023 1 S Unorotecnd. PnUR c.000t l S Unprotectrd, PRUR t ).OOO</ S Unprotacma. PsOtr -i , S PnOTt, PnUU ) PnOTt, PhUR to PnOTr. R OTr t s PnUR. PhUR t0.050l PnUR. PtOTr ( PhUR. h0tr? t0.050!,9150!

158 ANOVA Table for U. Chang8 in MAP at HUT2ae Scfiette tor change ln MAP rt HUT2a-e Enecr: GpeRmentd scheduh Significance Level: 5 tl ROT,. RUR ~ h OTr. Ps Ofr ! 9978 I PnuR. RUR [ ; 4976 : PnuR. %OTr RUFI. PsOTr Scheff* for U. Chang* in MAP at HüT2a-c Ulrcr tilt position Signfffcanca Lev8l: S K

159 ANOVA fable for Y. change in HLBP it HOT OF S m ot Squares Mean Square F-Vabe P-Value Lambda Pow er Subiect SBJ Gperimrntal scneduie J t t tperunentai teneclub ' Subyct 32 t880.84s Schatie toi # change In HLBP ri HDT Utect: Experim rntrl s Chedule Slgniflcrnce Lrvel:S K Unprotec ted, PnOTr Unprotectrd, PsOTr Unprotectrd. PnUR Unprotacted. PhUR PnOTr, PsOTt PnOTr, PnUR PnOTr. PhUR PsOTr. PnUR PsOTr, PhUR PnUR, PhUR

160 ANOVA Table lar % thange in HLBP at HUT28 OF Sum a t Suuares Mean Square F-V alur P-V aiue Lambda Pow er suarct Exprrunental Schedub bperimentai ScneduY *'subpct I r JS ? O * Scheffe fat K ekingr in HLBP rt HUT2r Elfect: Errpr rim entrl Scbeduk Slgniflcano Cevel: 5?C Unprotected. PnOTr Unprotected. Pt OTr Unprowcted. PnUR Unprotsctrd. PhUR PnDTr, PsDTt PnOTr. PnUR PnOTr. PRUR PsOTr. PnUR PsDTr, PhUR PnUR. PhUR

161 ANOVA Tabla for X chango in HLBP at HUTZr=c OF Sum al Suuarrs Mean Suuarr F-Value?-Value tamada Paw er Subiec! I ! l I l I, Exgenmental scnedub i i tuet!,0006 ; i -984 Gperrnenill scnrduk ' Sublact, t07 I l f ~ posmn t 1 2; / t ' c.oaai! 169.0a4 f i TO~ posieion '~ueyct t6 ZSS.O~S t t 1 l Gprrimeniri scnaaule * ~ ipasdan t I 6; I 2.160:.0425! 17-2eoj.313' Gpenmental scnrdub 'fpl posnbn 'Su., f ( l I t Schrtfe lot?l chinga in HLBP rt HUT Za-c EIlict: Eirprrim ontrl sehadula Stgniflcante LeveI: 5 K unprotictea. h ~ f r Unprotictrd. ROTr Unproiictod, FnUR Unprofictod. MUR PnûTr. PsOTr FnOTr. RUR Maan Dut. Crd Diif P-Vaaio Scnattm tor S Chang@ in HLBP at HUT2a-c Elteet: T IIt pos ltion Signittcinem Laur 1: 5 K Mtrn OU. Cnt, DHI P-Vaiur nma. num O ota* ) O a.rrt I ta [.9@ ) f.7888 PnOTr, AiUR ( go18 1 ROTt. MUR ROTr, PhUR tUI t 0.44t i PnUR. RiUR S S S HüT20, HUT2c

162 ANOVA Table toi 5 change in HR at HOT OF Sum ot Squares Mean Square F-V ahre P-V aîue Lambaa Pow er SubNct Expetimeniai scnrdule Expetuneniai scheduk ' SuOrct J t 8M ! ? 1

163 ANOVA Table for?l change in HR at HüTZ8 OF SumatSuurtas ManSquarr F-Value P-Value Lambda Pawer Subjrct schedui. Expetuneniri scneduie ' Suoyct t.o90 102t t t O ,865 Scbeffe lot?c cnrngo in HR rt HUT28 Effect: Exp*rlm rntrl scitedu te Slqniticance LI val: 5 S PnOTr, PhUR PnOTr, PI OTr PnUR, PRUR PoUR, PsDTr PhUR. Ps Ofr m4 1

164 ANOVA Tilt. fût?c Ch8nga In HR i t HUTÎr-c Submct Gprmrntal scneaur Gprnrmntal scneauu ' Subrct rat posdion Tiit pasdbn * SuQ8ct Goenmental scnaauu œtdl pasnion bprrtmrntai scneauu pasfion ' Su-. Sckeffr (or % chrngr in UR rt HUt28-c Utrct: Experim rntrl rchrdula SlgnYlcancr tavrt: S K Mean DUl. Cr& Odt P-V ab8 Unprotrctrd. PnOTt unprotrctra. UR s i.5180 ( unprotrctea. RUR t1.31~ 1. 9 ~ 7 Unprotactee, PJOTr t ~n07r. UR r.62ti t1.31~1.nul Sckrttr tar % change in HR at HUT28-c Ellmct: Tilt poa ition Signitieanca Lave 1: S X Man Dilt. Cnt. Dftt P-Vaîur Har. HUT2b O790 Hü72a, HüT2c I s H U ~ Z ~. H ~ C j 1.r4s J.owi

165 ANOVA Table for X change in Zo ai HOT Subirct Exparimental scnedul8 Erperunentai rcneauk ' Subirct OF Sum ot Squares Mean Square F-V alue P-V akre Lambda Pow er t as ,0498 T I Schette for K change in to at HDT Eltect: Erperlrn enta1 s chedule Signiflernce Lavol: 5 % Unprotectrd. PnOTr Unprotrctad. PnUR Ungromctrd. PhUR tlnptairclra. PsDTr FnOTr, PnUR PnOTr, PhUR PnOTr. ROTr RiUR. PhUR PnUA, Ps OTr PhUR. PsDTr, Meln Ott. Cric. Oif t P-V alue -.ne j r.038!.9428 j -.O ,9999 I -A i l t J405 j mia I t.03a i 9753 l

166 ANOVA table for Ti change in Zo at HUTta OF Sum of Squares Mean Suuare F-V alue P-V alue Lamoaa Pow er Subpct 8 2S.tOs 1 5.r 38 Gprrimentai scheduh c t.a00 Gperimrntal tcnrauie "subpct (.463 Scheftr!or % change in Zo rt HUT28 Utect: Erprrimrntal schrdulm SIgnificrnce Lave 1: S K Maan Oitf. CrC Ouf P-Vrtue Unprotscled. PnOTr Unproteciad. PnUR Unprotecled. hotr PnOTr. PnUR -.sr0.04a i i. -- PnOTr. ~ U R r.oca[ -.ogi~is PnOTr. PsOTr -499 ( t.o PnUR. PhUR PnUR, PsOTr PhUR. PsOTr ~ s

167 ANOVA Tabla for K change in Zo at HUTta-e OF Sum ot Souares man Square F-Vatue PVatue tamoaa Pow er Suoiect Exgerunental ScneduU Gprrimental senrouir ' Suoiect Xi1 potdion TJt position * Suolect Ggerunrntal scneduto ' Tiü posubn Etpinmental ScneduC ' Eit poslion ' Su... Schette for % change in Zo at HUT28-c Utrct: Exprrimantrl schedula Slgnitlcrncr Laval: S K Mean Oiit. Cm Wf PVaLie Unorotrcted, PnOTr 4. l x t.~tr! C O O ~ ~ ~ S unprotectra, R~UR i COOOI s unprotrctea. RUR i 1 COOOI s Unorot~ctea. ROT^ t-oit1 c.0001 s mon. P~UR t.a1 I.9733 i ROTr. AiUR s t.01 t 1. S m P~OT~. PSOTI RUR, RUR -.312[ t.ot AiuR. ROfr RUR, ROTr i t.or I Sch8tl0 tor K ehrngo In Za at HUT2a-c Elfe et: Tilt pos itlon Signttlcancr t a val: 5 X man Oiff. Crit, OUI P-Vaba HVTZa, HlRb ma. nunc Hmb. HUtZt

168 ANOVA Table for?c change in SI rt HOT OF SumofSauores Meansauare F-Value P-Value Lamoda Power

169 ANOVA T ablr for?" change in St rt HUTZr OF Sum ot Squares Mean Square F-Vahrs P-V alue LamOaa Pow sr Subject Exprrunrntai scnruuk Exgerimrnnl scheaule ' Subjact 8 O t ,

170 &NOVA Table for % chrngr in SI 8K HUTZa-c OF Surnot Squares Meansauare F-Vabe PVahie Larnoea Powei Subpct Ggenriuntal scnrduk Exornmrntal scneduie ' Subpct nt positbn Kit posdbn ' Suopct Gornmrntai scnrduk ' Tilt 00stti0n Exgrrmntrl scnrduie ' tm posumn 'Su.,

171 ANOVA Table for % change in Ct at HOT OF SumotS~uares MeanSauare F-Value?-Value Lambda Pawer Subpct Gperimental scnaduk Experimentol scheduk ' Subpct i 5 ( J t f.683.go91 32 ôo t t 6 l [

172 Subpct Gperunental scheduk Expwirnenlal sct~m#uhj Subpct OF Sum ut Squares Mean Square F-Value P-Value Lambda Paw et J ; ( I a00 I Schefto for % thange In Ct rt HUT2i Eltect: Experimentrt sshedul8 Signitltance Level: 5 % Unproisctid. PnDTr Unprotected. PnUR Unprotectid, PhUR Unprotected. PsDTr r Main Dl! I. Crit. OUI i P-Value a PnOTr. PnUA O471 1 S PnOTr, PhUR ,9993 PnOTr, Ps OTr t A095!.om s 1 PRUR. P ~UR -20~74 22.~4~ PnUR.?SOT r -1 t, i A136 1 P~UR, PsOTr i 22.54s i.7526 I

173 ANOVA Tabla tot % chingo in CI 8t HUfZa-t CC Sum of Squares *an Square &Value Wabe tamabr ~ orr w Subjlct Gpenmantal scnedula bpemrntai scheaute ' Suorec! 8 O 32 t t TOI posuian n r nt gasdion ' Subpet Gperimrntl scneauir -Tin gositkn b Gprrunenirl scneaula -Tin position 'Su tl S.tt6 / t / 1 1.~04 t ta3.ooo~ 6.0So , ao4 33.~0,992 Schotto tor % change in Cl rt HU728-c ~ftoct: TII~ position Stgniflcrno Laval: S K Me8n Ddf. C a Dwf HUT2a. HUTZb HUT28, H1172C Hrnb. Hmc PV~kll

174 ANOVA tabte for subjact Gperirnental scnedule Gperirnental scneaula "~ub~ect change in TPRl rt HOT OF Sum ot Squares Mean Square F-V aiue P-V aiue Lambda Pow er toxrt~ t 8.265, 32 t t r.747.t 37

175 ANWA Table for?i change in TPRl at HUT28 OF SumatSquares MeanSquare F-Value P-Value Lambaa Power SubPct t 8 t.908 Gperimrnial scheduk Gpetimental scnedub ' SuDbct, Schrtte tor?l cnrnge In TPRi 8t HüTZa Utoct: Experim ontal sclwduk Signillcrnce Leve 1: 5 5 Me8n Oitf. Crit, OUt P-Value Unprolected. PnOTr ( j / Ungrotrctad, PnUR Unptotected. PhUR PnOTr. PnUR PnOTr. PhUR PnOTr, PsOTr PnUR. PhUR PnUR. Pt OTr PhUR. PsOTr

176 ANOVA Tabla for X change in T PRi ri HUTZr-e OF Sum ot Sauares Mean Sauar* F-VaLe P-V ab@ Lamnaa Ww er suoirct Gp@rnnentai seneaulm Gpemntal scneauk ' Subpcr Tüt posdbn Tiït posdbn ' Suoyct Gperimental scneauy ' Tin oosnbn Gpernunui scneauu ' TIR oosftion ' Su., Utrct: Tilt pos itlon

177 ANOVA Table for X change in FBF at HOT OF Sumat Squares Mean Square F-Value P-Value Lambda Pow et Subject 8 54S Expetrimental scneduie ! ?62.Si Zia 1 Gpethrntai scnoduii ' SubNct 32 t

178 ANOVA Taisle or# Ch8ng8 fn FBF at CIUT28 OF Sum ot Squares Mean Square F-Vatue P-Valu8 Lameaa Pow sr Suoieet Gperunenrai Scneduk Gperirnantal Scneauk ' Subrc t a 1 4 r92~0.~71 t82rs _ 23 t rt JS I.O007 ( I I A.90 t? Siqniftcrncr LavmI: 5 % Main Oiff. QW. OiH P-Vahre UnDratoctea. PnOTr O Unprotacma. PhUR Pn DTr. Pt OTr PnOTr. PnUR PnOTr, PhUR RDTr. PnUR RDTr. PhUR PnUR. PhUA [ 131.a68 1.0O10) S t O.9298 / t.O66 1, t t.0661.O142 13t.0661, tOO? S 13 1.O66 1.O345 1 S

179 ANOVA TaBir tor?l crrng0 FBF it HUTta-e OF Sum ot Sauares Man Squara F-Vaiuo P-Vakro Lambda POW er SubiOtt Exprnmentzi scneaul Gprrmental scnrnaui. ' SuPyct TiIt postikn Tiit position ' SuBMct tprnmrntal scnedule 'TR positkn GportmanUl senadule ' Tüt positbn ' Su- Scha t k tor % chingr In Fût rt iiutz8-e Eltact: Erperirnontrl sehidulr Slgnitkinen LovaI:S X Morn Oift. Cr#. Dut P-Vaha PnOTr. ROTt PnOTr, RUR MOT?. PhUR PsOTr. RUR ISOT~, R\UR PWR RUR S. S I.97otl ï7.491 i.olt0 1 S î.491 J n.rw I.O424 s -n.zs81 n.wf.on9 Scnrtte tor K changr In F6F at HUT2r-c fftrcr: Tilt pas Non Slgnlttcrnce Love1:S K a HlJTZb. H ~ C Moan Oilf. Crtt. DI1 &Vaka HUT2a. HU~ZL ' rg.ttot ro.not.o~tj~s nuna, nunc n.na 1 ~o ooor s

180 ANOVA Table for?c change in FVR rt HOT OF Sum of Squares Mean Square F-Vakre P-Value Larnoua Pow er a t ogs.3~ , , O

181 ANOVA Tabla tar X change in N R at HUT28 OF Sum a! SqulfeS Mean Square F-Value P-Value Lambda Pow er Subiect ) 3SS &petunentai Scneduk 4 (l(r15.11j 2.f.UJS.O Gperunenul Scnrduk ' Subrct

182 Schetfi for % change in N U it HUT28-e EItect: Exporim rnirl SchOdula SignifIcrnca La va 1: 5 2 Ml8n OUI. CN. Odf PVak* Ungonietid. ROTr Ungon8ctod. R\UR Un~ort8ttrd. PhUR RM~. RUR -9.43tT i PnOTr. RUR ROTr. PnUR ROTr. RUR PnUR RUR sche tfa ïar % chingo in WR it nuni-e tmct: ~iit position Slgnltlcincr Lrvrl: 5 X

183 Appendix C Means Tables

184 Means Table fur Dacrersa In SBP (dp) Eifect: ExparTm entrl schedule Count Mean Std. Oev. Std- Er;. Unprotected Pn OTr ? PnUR RiUR Means Table for Tirne of S8P recovery (dt) EHect: &mrimental schedule Count Mean Std. bu. St6 6r. Unprotected RiMr RCrrr hm Ftlm

185 Means Table for % change in SûP at HCIT Effect: ttperimental schoduk Count Mean Std. tbv. Std. Er. ünprotected mm hw Riw &ûtr Means Tabk for 96 changa in SBQ 1 HW2a Wect: Experim ental sch8duk Count Maan Std. Dev. Std. Br. Unprotected '76 mm RiUR RUR S RMf Means Tabla for 96 change In S8P at HUT2a-c Bfect: t3perimental schodule 'nit position Caunt Mean Std Dev. Std. Er. ünprotected, m a ünprotected, HüEb Unprotected, Wl2c mm, Hum Rimr, m Pnmr, m c RüR, m a Rrn MllZb mm HURC PhüR WT2a mufl Hum PhUR Wï2c BIJTr. iwza &m. m RWr, rn

186 Means Table for % change in MAP at HDT Effect: Erperimental schedula Count Mean Std. Dev. Std. En. Unpmtecteâ PnOTr, , _ PnUR L PhUR Means Tabla for % change in MAP at HUT2a Effect Experfmantal scheâuk Count Mean SM. Dev. SM. En, Unprotected PnDTr PnUR PhUR PsDTr Means Tabla for 56 change in MAP at HUT2a-c Eftect: Experfmental sttiedule ' Tilt position Count Mean Std. Dev. Std, En. Unpmtecteâ, Unprotected, HUT2b Unprotected, HUT2c PnDTr, HüT2a PnDTr, HUT2b PnDTr, HUT2c PnUR, HUT2a PnUR, HüT2b PnUR, HüT2c PhUR, HüT2a PhUR, HüTZb PhUR, HUT2c PsDTr, HUT2a PsDTr, HUT2b PsOTr, HüT2c

187 Y oins table for?c thln40 in HLBP at HOT Efloct: Expr rfm ont81 schodulr Count Mean Sld. Dev. Std. br. Unprotrcted Pt DTt PnUR PhUR Means Tabk for %change in KBP at W 2a ffect: ttperimental Scheduk Count Metan Std Oev, Std, Gr. tkiprotected ROTr ROTr Means Table for SC change in KBP at M2a-c Eftact: brperimental scheduk 'Tilt position Count Mean Std. bv. Std. Er. ünprotected, HVrZa ünprotected, HU2b Ihiprotected, W Ec mmr, WRa RMr, WEb mm, m c Psmr, m FSMr, WEb RûTr, lm2c WUFi, HüTZa

188 Means Tabk for K change in HR at W Bfect: hperimental scheduk Caunt Man Std. Dev- Std. Br. tkiprotected Ffiofr RUR t7 RUR R[JTr s Means Table for % change in CCI at W2a Bfsct: Ewperfmental schedule Count Mean Std. Oev. Std. &r. llhprotec ted Riüir RUR RiUR ô RMlr Means Table for % change in HR at WT2a-c Effect: Ewperfmental scheduk 'Tilt position Caunt Mean Std. Dav, Std Br. Ulprotected, MITZa lhprotectad. Hül2b ünprotected. HURc mmr, MIT2a hm. m mmr, m c RüR, m a hur r n b mm m c RüR, liwï2a RUR l-ul2b FhUR Wi2c Psmr, Hum RDTr, H m Rmr, HUPc

189 Means Table for % change in Zo at îm Effect: Ehperimantal schedule Count Mean Std. Dev. Std Er. Uiprotected , PnUR niur RMr 9-61a O Means Tabk for % thanga in Zo at W2a Hfect: Exparimentai schedule Count Mean Std. bv. Std Br. Unprotected mmr RIUR.954 RUR 12t 8 I%Dt 1226 Means Table for %change in 20 at WZa-c Effed: trperim enta1 schedule 'Tllt position Count Mean Std. Dev. Std. tir

190 Means Table for % change in SI at W T EHect: ttperimental schedule Count Man Std. Dev. Std. Er. ünprotected Rmr mm RiUR RMr Means Table for % change in SI at W2a Effect: Experimental schedula Count Man Std Dev. Std, Eir. Unprotected RUR ,459 RiUR i3mr Means Table for % change in SI at M2a-c Effect: Etparimental schedule ' Tilt porîtion Count Man Std. Dav. Std, Er. Unprotacteci, m a ( ( Unprotecteci, WRb Unprotected, Wi2c mm, Hul2a mdtr, r n b mmr, m c

191 Means Table for %change in Cl at HOT Effect: ttperimental scheduk Count hhan Std- *v. Std. Er. Unprotected RUTr nlm PhUR RMr Means faôk for %change in CI ut M 2a Btact: tiperimental schedule aunt Mean Std. Dev- Std tir. Unprctected nia RiUR Psmr Means Table for %change in Cl at HVT2a-c Effect: Etparimental schedub nit posttion Count man Std. Dev. Sld. Br. Unprotected, HUT2a ünprotecteâ, Ikiprotected, WRc mmr, Hum hmr, HLlf2b mmr, m c mur m mur m mu?, m c mu9 HUT2a mur m PhUF1, m c RMr, Rrn. m RüTr, WC

192 Means Table for '/o change in TPRi at k M Hfect: trperfmental schedute Count Mean Std. bev. Std. Er. Unprotected RMr ma RUFI RôTr Means Tabk for 96 change In TPRf art M2a Hfect: Expeiimentai schedub Count Mean Sld- Dev. SM. Err. Ikiprotectad mm RUR niur Rüïr Means Tabk for %change In TPW at HVT28-c Effect: trperimental schedule 'Tilt position Count Man Std Oev. Std. Er. Unprotected, m a Unprotected, Wl2b Unprotected, WT2c mm, l-kn2a mm, m RDTr, HUEc RUR m a RUR HlfT2b mm m c RiW. iiui2a RiUR r n b

193 Means Table for %change in mat Wf Hfect: Experimentaf rcheduk Caunt hari Std. Dev. Std Er. ünprotected ,470 RNr WUR RUFl 9 T Means Tabk for % chang8 in FBF at M2a Bfect: tiperimental Schedule Count Mean Std. Dev. Std. Er. Uiprotected PhUR Means Table for %change in F6F at M2a-c Effect: merlmental schedule ' Titt position Count Mean Std. Dev. Std, Br. Unprotected, W a ünprotected, MIT2b ünprotected, WEc FnûTr. Hüb mmr, ntt;ib WMr, M2c mm. rn

194 Means Table for % change in FVR at KIT Bfect: mperimental seheduk Count Man Std. Dev. Std. Er, Means Table for 36 change in WR at M2a Efett: me rimental Schedule Count Mean Std. Dev. Std hr. Ikiprotected kur RUR Means Table for % change in FVR at M2a-c Bfect: &perimsntal schedule ' TlIl por Mon Count Man Std, Dev, Std. &r. hportected, W a Unportected, HüT2b Unportected. MZT2c mm, wi'2a mm, m FnMr, WTZc Psmr, wm Rrnr, HURb Bmr, WC hur Hum hur m mur m c RtüR, Hüï2a Phm. HLiIZb Ftlm m c

195 Appendix D Consent Form

196 D a m Human Ethics Consent Forni Protocol # L Evaluation of a Subject's Physiologicai Responscs to Non-lineu G-suit and Positive Pressure Bmathing Schedules During Low Intensity Push-Pull Transitions Prinaple hvestigator : William Fraser, H/ SAlLSS Team Associa te Investiga toc Dr. Len Goodman APPC; / ALS Associate investigator: Michael Colapinto APPG/ALS 1, (address and telephone number) hereb y vol&eer to participate as a titsubject in a DC6 experiment to study the effects of noniinear Gsuit and breathing pressure schedules under low-intensity Push- Pull transitions. I have read the attached information package on the experimentd protocol and description of risks, and have been infonned to my satisfaction of al1 the risb -ated with the experiment and consider these Nks acceptable. in addition, I undeatand that this study, or any research, may involve risks that are currently unforeseen. I understand these risks. For CF Members only: I understand that 1 am considered to be on duty for disaplinary, administrative and Pension Act purposes during my participation in this experirnent. THIS DUTY STATUS HAS NO EFFECT ON MY RICHT TO WITHDRAW FROM THIS EXPERMENT AT ANY TIME 1 WISH AND 1 UNDERSTAND THAT NO ACITON WILL BE TAKEN AGAWST ME FOR EXCERCISING THIS RIGHT. Ali of the cardiovascular measurement techniques are non-invasive, and have been safely used in previous DCIEM investigations (Protocol L#l63)- A detailed description of the sensors are sumrnarised in (11. The electronic Anti-G valves have been used in previous DCIEM experùnents and found to be safe, providing appropriate mechanical safeguards are taken (5-71. This device is designeci and engheered to be safe under mat possible scenaiios, including power loss, runaway motor, and control system. However, there is a remote possibility that these systems, even with their built-in redundancies, could fail. There is a remote possibbity of injury (if al1 the safety valves (two mechanid and two electronic safety valves), and software safety checkhg program fail at the same tirne) by applying too hi& pressure in the Cniit and the respiratory systern. The risks of PPB are weu known, and dommenteci eisewhere (21. Minor risks include pe techial hemorrhage, loss of central blood volume and fainting, breathing discornfort and facial dixomfort. The pressure fiom the Gsuit rnay cause ümb tingling and changes in breathing patterns, particularly in the head-dom tilt posture- More serious but rare complications can indude fainting, pulmonary barotrauma resulting from inadequate thoracic counterpressurùation, with introduction of air into the arterial circulation, and cardiac arrhythmia. Furthemore, PPB in the head-down tilt posture might cause gastrointesansl complications such as gastric reflux, and in rare cases, aspiration of stomach contents with axphyxiation if preceded by choking and vomiting. Minimization of these Mks is ensured by preliminary pilot studies, proper rnedical screenins thorough subject training and habituation, a redundant faiî-safe pressure delivery system, and the weacing of properly fitted Anti-C-suits and thoraac counterpresme gannents, and conswnption of a standard liquid meal prior to al1 experiments whkh wüi be supplieci by the investigaton. Suction equipment will be available Yi cases of aspiration of stomach contents. I understand that a medical intemsew, examination, and tesb will be required before my participation begiris. I hereby consent to the rnedical assessment outlined in the protocol and agree to provide respomes to questions that are to the best of my knowledge, buthfui and complete. Before 1 begin any experimentai sessions, 1 must inforni the investigator of any changes to my medicd stahis since my initid assessment inciuding bit not IUnited to virai illnesses, new prescription or "over-the-counter" medications, and new Nk of pregnancy. 1 have been advised that the medical information I reveai wiii be treated as confidentid ('Protected 8' LAW CF Security Requirements) and not revealed to anyone other t'an the investigator without my consent expect as data rmidentified as to source. 1 understand and agree that should I require

197 medical treatment as a result of this study, this will be provided or coordinated by the physician assigned to this study. I understand that a medicai officer will not attend the experimental sessions, but will be on-caii and in the immediate vicinity in case of emergenàes, and hereby consent to whatever medical intervention deemed necessary by the attending medical perso~el or their consultants. I am aware that 1 wiii participate one training session of 2 houis length, and in four experimental sessions of 3 houn length (induding subject preparation the) involving approximately 20 individual runs consisting of G-suit pressurization up to 35 psi, PPB to 40 mmhg, and ült-table rotation while king monitored by a number of cardiovascuiar and cerebrovascuiar instruments as outlined in the protocoi. 1 have been assured that any personal information conceming me that is revealed in connection with this study will be kept in strict confidence except as data unidenafied as to source. I agree to: (i) not consume any alcoholic beverages within 24 his of each series of experiments; (ü) have a restfd night evenhg the night before a test; (iii) perform no heavy exercise on the day of a test; and (iv) abstain from smoking, coffee, coia beverages and chocolate in the 3 hr pend before a test, and consume only the supplied Liquid meal in the hour preceding i t I understand tha t a blood donation les than 30 days in advance of commencement of experimentation are contraindications to my partiapation in the study. For female sub jects: I have been infonned that that this experimental protocol could be potentiaily hamihil to a fetus. Thetefore 1 consent to the administration of a pregnancy (senim/blood) test as part of the medical procedure prior to the commencement of this experiment 1 undentand that this result and al1 discussion pertaining to this matter WU be treated as confidential between the physician and subject. If 1 have concern regarding a passible pregnancy 1 will consult a DClEM physician before undertaking or resurning any phase of the experiment. Furthemore, 1 wiii take appmpriate precautions to prevent pregnancy for the duration of the experiment. This consent is voluntary and has been given under circumstances in which 1 can use free power of choice. 1 have been infomed that I may, at any time, revoke my consent and witmraw from the experiment. In the event of a loss of consciousness epwde as a result of PPB exposure, 1 shall refrain from dnving or operative heavy machinery for a period of 4 hrs foliowing the experimental session. Y hansportation is required because of this recommendation. the principal Uivestigator(s) shall make such arrangements, the cost of which, where necesary, will be borne by DCIEM. Also, the investigators, their designate, or the physician(s) responsible for the experiment may tenninate the experiment at any time, regardles of my wishes. Votunteer: Name Sigriii hue; Da te Witnes Name Signahue Date This subject is certified fit to participate in this experiment as outlllied in the protoc01 with the Limitations appended below: Section HeadKommanding OfficedUame Signature Date