Contrary to this expectation, the removal of the fleece, or a large area. Babraham, Cambridge

Transcription

1 764 J. Phy8iol. (1963), 168, pp With 7 text-ftgures Printed in Great Britain INHIBITION OF THERMAL POLYPNOEA IN THE CLOSELY SHORN SHEEP BY J. BLIGH From the A.R.C. Institute of Animal Physiology, Babraham, Cambridge (Received 8 October 1962) The onset of panting in sheep can occur almost immediately upon a rise in ambient temperature and in the absence of any rise in the temperature of the blood supplying the brain (Bligh, 1959). A subsequent slow drift in deep body temperature in either direction is apparently without effect upon the respiratory response to ambient heat, and it has been concluded that the onset and control of thermal polypnoea can depend entirely upon a peripheral thermal stimulus acting upon receptors at some relatively naked external surface. This conclusion has been confirmed by Waites (1961, 1962), who provoked panting in the ram by exposing the scrotal skin alone to a warm environment. However, there was only a small rise in respiratory frequency when an equivalent area of shaved skin on the flank was similarly heated. Waites (1962) has therefore suggested that the peripheral warm-receptors are concentrated at specific areas, and are not distributed uniformly over the external surface of the sheep. If this is so, it might be supposed that close-shearing of the sheep would have little effect upon the onset of panting or the level of panting achieved when ambient temperature is raised; the exposure of even a sparse concentration of warm receptors after shearing might result in a more rapid onset of panting or a greater rise in respiratory frequency. Contrary to this expectation, the removal of the fleece, or a large area of it, results in a depression of respiratory frequency at 200 C and a long delay in the onset of panting when the ambient temperature is raised to 420 C (Bligh, 1961). In this paper the phenomenon is described and discussed in greater detail. METHODS The experiments were made on thirteen Welsh Mountain sheep of which ten were wethers (castrated rams) and three were ewes. They weighed between 25 and 40 kg and were between 7 and 36 months old. No differences in behaviour were noted between animals of different sex, weight and age. When the animals were sheared, partially or totally, this was done with Oster small animal clippers (Model A2) and a fine (size 40) head. The head needed to be frequently dipped in a 2: 1 mixture of paraffin and light oil to prevent it from becoming clogged with

2 RESPIRATION OF SHORN SHEEP 765 wax from the fleece. With this precaution, the fleece was cut evenly so that only 1-2 mm of the wool fibres remained above the skin surface. When the animal was kept shorn, the clippers were re-applied twice weekly. To re-insulate a shaved area from the environmental temperature effects, it was covered with a coat tailored to fit the shorn area. This consisted of three layers of gamgee (cotton-wool between two layers of cotton gauze) which made a coat cm thick. The coat was held on by tapes to allow rapid removal when required. In most of the animals a copper-constantan thermocouple was chronically implanted within the lumen of the brachiocephalic trunk. The thermocouple wires were brought out through the skin in the neck region to terminate on a Perspex button (Bligh, 1959). This permitted the implanted thermocouple to be connected to a temperature-measuring system during test periods, and for the temperature of the blood passing through this vessel to be measured with an accuracy of 0-10 C. The surgical intervention did not modify the respiratory effects of shearing. Trunk and ear-skin temperatures were also recorded with the same degree of accuracy by means of fine (40 S.W.G.) thermocouples attached to the skin by a blob of latex beneath a small thin rubber patch. Respiratory frequency was measured by means of a stethograph belt and an ink-writing tambour on a kymograph. During the test exposure periods in a small climatic chamber brachiocephalic trunk blood and skin-temperatures, together with wet-bulb, dry-bulb and wall temperatures, were recorded at intervals of 5 min. A 2 min recording of respiration was made also at 5 min intervals, and a representative portion of the record was subsequently counted. The sheep were kept in pens the ambient temperature of which was kept between 17 and 230 C during the periods when the experiments described in this paper were made. During brief warm spells of weather, when the temperature in the sheep house approached 250 C the respiratory effects of shearing became unpredictable and less well defined. The results from experiments made under these conditions were discarded. For test exposures to an abrupt rise in ambient temperature the sheep was brought to the laboratory in a trolley, so as to minimize disturbances to metabolism. It then stood tethered within tubular steel stanchions in the climatic chamber without access to food or water during the test period, which did not exceed 3 hr. After the thermocouples and stethograph belt had been attached to the animal, the chamber door was closed and the animal left undisturbed during the experiment. All measurements were recorded outside the chamber. The wall and air temperatures of the chamber were kept at during the first 30 min. Ambient humidity was not controlled but remained between 30 and 50% r.h. Wall and air temperatures were then raised to 420 C, the change being completed within 20 min. Again, humidity was not controlled, but changed to between 16 and 22% r.h. This ambient temperature was maintained for so long as was necessary to establish a steady rate of thermal polypnoea. For the i.v. infusion of adrenaline and noradrenaline, a polyethylene cannula was introduced down the lumen of the jugular vein and left in situ for the duration of the experiments. It was flushed daily with heparinized saline and kept stoppered. For the infusion, the cannula was connected through a Dale-Schuster perfusion pump to a supply of sterile pyrogen-free isotonic saline containing adrenaline or noradrenaline 10 jug/ml. This was infused at the rate of 5 ml./min (50,ug/min). In some experiments the ambient temperature was allowed to fall after having been maintained at 420 C. It fell by 90 C during the first 15 min and a further 3.-5 C in the second 15 min. In some other experiments a cooling pad measuring 30 x 15 cm was applied to the shorn area after thermal polypnoea had been established, the ambient temperature being maintained at 420 C. The pad was perfused with a refrigerant so as to lower the skin temperature beneath the pad, as measured by a thermocouple attached to the skin, to 150 C. Each observation reported here was made in at least two series of experiments on different animals. Pyil 6 49 Physiol. 168

3 766 J. BLIGH RESULTS Total removal of the fleece The pattern of change in respiratory frequency before and after close shearing when ambient temperature was raised from C to 420 C is shown in Fig. 1. Whereas the respiratory frequency of the unshorn animal was about /min at 200 C and started to rise almost immediately when ambient temperature was raised to 420 C, after shearing respiratory frequency was depressed to a steady value of 16-20/min at the lower ambient temperature, and when ambient temperature was raised there was a delay of some min before respiratory frequency started to rise. It then rose rapidly to achieve a level equal to or somewhat above that of the unshorn animal. In some animals the delay persisted for up to 70 min. Whereas the skin temperature beneath the fleece of the unshorn sheep was closer to deep body temperature than to ambient temperature when the latter was 200 C, after shearing skin temperature was about 100 C lower, being then closer to ambient than to deep body temperature. When the ambient temperature was raised to 420 C the skin temperature of the shorn animal rose rapidly, so that after 15 min it equalled that of the unshorn animal at the same point in the experiment. It then rose to and levelled out at a higher value before there was any increase in respiratory frequency. When ear-skin temperature was also recorded, it was found that after shearing this, too, was depressed at 200 C ambient temperature, although the ears were not clipped. This indicates a state of generalized peripheral vasoconstriction after the removal of the fleece. In the example given in Fig. 1 the depression of respiratory frequency at 200 C after shearing was unaccompanied by any significant change in deep body temperature. The difference between the two records of deep body temperature at 200 C is no greater than might occur between any two experiments on the unshorn sheep. However, the effect of shearing upon brachiocephalic trunk temperature varied considerably between animals. In general there was a tendency for deep body temperature to be lower after shearing, but the depression of respiratory frequency was not dependent upon a depression of deep body temperature. When the ambient temperature was raised to 420 C there was sometimes a sharp fall of up to 0.50 C in deep body temperature. This could be due to a reflex peripheral vasodilatation resulting in an influx of cooled blood from the peripheral tissues into deeper tissues. Deep body temperature would then often rise steadily during the period when respiratory frequency remained low and level out after panting had started. The final level of deep body temperature was dependent largely upon the extent of its initial fall and was not always above the mean level at 200 C ambient temperature

4 RESPIRATION OF SHORN SHEEP 767 when respiration started to rise. There was no evidence to suggest that the largely predictable effect of shearing upon respiratory frequency was causally related to its quite variable effect upon deep body temperature. Covering up and re-exposing a shaved area of skin The essential details of the changes in respiratory frequency shown in Fig. 1 occur if an adequate area of fleece is removed from the back of u u L_ o o vi 39 V 'E ==01 co C 200 v.0 C cr a 100 m IA 4) Time (min) Fig. 1. Comparison of the brachiocephalic trunk temperature, trunk skin temperature and respiratory frequency of a Welsh Mountain ewe before ((O) and after (-) close shearing of the fleece when ambient temperature is changed from 20 to 420 C. The vertical line marks the point where ambient temperature started to rise. 49-2

5 768 J. BLIGH the animal. When an area of cm2 (50-60 x 50 cm) is closely shorn, respiratory frequency is fully depressed at 20 C, and there is a delay in the onset of panting when the temperature is raised, although the delay is of shorter duration than when the whole fleece is removed. The experimental advantage of a hemi-cylindrical shaved area across the back Cc "0 = -C4)._ utoce ea] E, 200 Ḏ U 0) cr Er 0 o.y 1 00I Vt 4) Time (min) Fig. 2. The brachiocephalic trunk temperature and respiratory frequency of a Welsh Mountain wether at 20 and 420 C ambient temperature with the fleece intact (@); after an area across the back 50 x 50 cm had been closely shorn overnight (0); when the shorn area had been covered with an insulating coat overnight and kept on during the test period (C), and when the shorn area was again exposed overnight and during the test period (?O). The vertical line marks the point where ambient temperature started to rise. of the animal was that this could be completely covered with an insulating coat, and re-exposed in successive experiments as required. In the series of experiments shown in Fig. 2 the shaved area was 2,700 cm2. The contrast between the respiratory pattern before and after

6 RESPIRATION OF SHORN SHEEP 769 the removal of the fleece when ambient temperature was changed from 20 to 420 C is similar to that in Fig. 1. When the shaved area was covered with the insulating coat overnight, and during the ekperiment next morning, the pattern of change in respiratory frequency had reverted to that of the unshorn animal. The cover was then removed and the respiratory response to the change in ambient temperature on the following morning was again that of the shorn animal. The brachiocephalic trunk temperature during these four experiments tended to be lower when the shaved area was exposed, but there was no sharp distinction in deep body temperature patterns comparable to the change in respiratory frequency when the shorn area was exposed and when it was not. Maintenance of the shorn state When a sheep was kept closely shorn for up to 122 days the pattern of change in respiratory frequency was indistinguishable from that of the newly shorn animal. Respiratory frequency remained depressed at an ambient temperature of 200 C, and when this was raised to 420 C the delay in the onset of panting of min persisted. There was no evidence of any modification to the respiratory behaviour which could be attributed to effects of acclimatization. Regrowth of the fleece When the fleece was allowed to grow again after a sheep had been closely shorn there was a progressive rise in the respiratory frequency at 20 C and a progressive reduction in the delay in the onset of panting when the ambient temperature was raised to 420 C (Fig. 3), though the time courses of the two changes were different, being somewhat similar to those shown in Fig. 4. When the thickness of the fleece had increased to 2 cm both the respiratory frequency at 200 C and the pattern of the change in respiratory frequency when the ambient temperature was raised to 420 C were restored to those of the unshorn animal. Removal of fleece in stages When the shorn area was progressively increased until the fleece has been totally removed, and the sheep was subjected to the test conditions shortly after each increase, the sequences of the changes in the respiratory behaviour were essentially the reverse of those when the fleece was allowed to regrow. The curves as the shorn area was increased were like those for the regrowth of the fleece (Fig. 3) but in the reverse order. At first there was a progressive reduction in the respiratory frequency at 200 C as the shorn area was increased, with no delay in the onset of panting when the ambient temperature was raised to 42 C. Only when about 30 % of the

7 770 J. BLIGH fleece-covered skin had been shorn, and when the depression at 200 C was almost complete, did the delay in the onset of thermal panting when the ambient temperature was raised to 420 C become evident. The duration of the delay then increased progressively as the shorn area was increased until the animal was completely shorn. When this experiment was repeated on another sheep a different area of fleece was removed in the first place, and the area was extended in a totally different order, but the results were essentially the same. The sequences of the changes in the respiratory frequency at 200 C and the delay in the onset of panting at 420 C shown in Fig. 4 were independent of the order in which areas of the fleece were shorn E ~,150- C o 100 4) Time (min) Fig. 3. The respiratory frequency at 20 and 420 C ambient temperature of a Welsh Mountain wether measured at intervals during the re-growth of the fleece after close shearing. The sheep was subjected to the test exposure at 1 (v), 13 (A), 26 ((D), 43 (O) and 49 (-) days of regrowth, and was kept at C ambient temperature during the intervening periods.

8 RESPIRATION OF SHORN SHEEP 771 Effect of the duration of exposure to the lower ambient temperature An adequate area of fleece was removed from the back of the sheep and this area was then covered with an insulating coat, so that the shorn area could be re-exposed to an ambient temperature of 200 C for a controlled U 0 a C4-. vf VV * A C 0~L)50 -~ o C l) 0 C B Co = 4o 38( Percentage of fleece shorn Fig. 4. A. The mean respiratory frequency of a Welsh Mountain ewe at 200 C ambient temperature, and the delay in the rise in respiratory frequency when ambient temperature was raised to 42 C plotted against the percentage of the fleece which had been closely shorn. B. The mean brachiocephalic trunk temperature at 200 C ambient temperature (@), and when a rise in respiratory frequency first occurred after ambient temperature had been raised to 420 C (A) plotted against the percentage of the fleece which had been closely shorn. I I100

9 772 J. BLIGH period before the temperature was raised to 420 C. For the longer periods of exposure when it was necessary to keep the animal in the sheep house the ambient temperature varied between 17 and 23 C. The depression of respiratory frequency occurred when the cover was removed from the shorn area of skin for as little as 5 min. The duration of the delay in the onset of panting when the ambient temperature was raised to 42 C, appeared to increase exponentially with the time for which the insulating coat had been removed from the shorn area (Fig. 5). 75 r. I-- m 50 v 0 C 0. 0~ 0 4) 9._ C 0 C (0 4) IV. 0 26hn I I 1*0 2* Log1o time (min) Fig. 5. The delay in the rise in respiratory frequency of a Welsh Mountain ewe on which a 2376 cm2 area on the back had been closely shorn when the ambient temperature was raised from 20 to 420 C, plotted against the log10 of the time in minutes during which an insulating coat had been removed from the shaved area, and the animal exposed to an ambient temperature of C immediately before the rise in ambient temperature. Intravenous infusion of adrenaline and noradrenaline The intravenous infusion of adrenaline and noradrenaline at the rate of 50 Jug/min for a period of 75 min which started before the rise in ambient temperature from 20 to 420 C and which continued until after the onset of panting, did not modify the duration of the delay in panting in the shorn animal.

10 RESPIRATION OF SHORN SHEEP 773 Effect of a fall in ambient temperature after panting had been establi8hed The climatic chamber used for these experiments was not equipped for a rapid reduction in ambient temperature. An exponential fall of ambient temperature from 42 to 30 C took 30 min. In the unshorn animal there 40 ] < 250 I~~~~~~~~~~~~~~~~~~. 200~~~~~~~~~~~~~.-~~~~~~~~~~~~~~o E4 V 20~ 0 sou c Time (min) Fig. 6. A comparison of the effect of an abrupt fall in ambient temperature from 420 C after thermal polypnoea had become established in the shorn ((OM) and unshorn (@A) Welsh Mountain wether, upon respiratory frequency and brachiocephalic trunk temperature. The vertical line marks the point where ambient temperature started to fall.

11 774 J. BLIGH was no decrease in respiratory frequency during the first 15 min of this period of cooling, but a reduction of respirations/min occurred during the next 15 min. In the shorn animal there was an immediate precipitous decrease in respiratory frequency as soon as the ambient temperature started to fall. The fall in respiratory frequency during the first 15 min was about 170/min and there was a further small fall to the basal level of less than 20/min during the next 15 min (Fig. 6). This marked difference in the pattern of change in respiratory frequency between the unshorn and shorn sheep could not be attributed to changes in deep body temperature. The continued high respiratory frequency in the unshorn animal as ambient temperature fell resulted in a fall of 0.50 C in brachiocephalic trunk temperature in the first 15 min in both experiments. The rapid fall in respiratory frequency in the shorn animal caused a sharp reduction in evaporative heat loss, and during the same period deep body temperature declined by 0 and 0.20 C in the two experimments shown in Fig. 6. The same abrupt fall in respiratory frequency occurred when a heating and cooling pad was placed on a shaved area on the back of the sheep measuring 15 x 30 cm, and the perfusion fluid through the pad was abruptly lowered from 42 to 15 C after panting was established at an ambient temperature of 420 C. The reduction in respiratory frequency occurred whether or not the ambient temperature was lowered simultaneously. DISCUSSION The pattern of change in the respiratory frequency of sheep after being closely shorn comprises four distinct features: (a) the depression of respiratory frequency to a steady low value at 200 C ambient temperature; (b) its persistent depression after a rise in ambient temperature to a level which would induce an immediate rise in respiratory frequency in the unshorn animal; (c) the ultimate termination of the respiratory depression by the abrupt onset of polypnoea in response to high ambient temperature and (d) an immediate fall in respiratory frequency to the initial steady low value when the ambient temperature is again lowered. A similar low steady rate of respiratory frequency of the shorn sheep at temperatures below 250 C has been recorded by Blaxter, Graham, Wainman & Armstrong (1959) and by Symington (1960), but these studies did not include the immediate effects of a transition from a low to a high ambient temperature, and the delay in the onset of polypnoea after a rise in ambient temperature has apparently not been reported hitherto. The depression of respiratory frequency from a labile rate of /min to a steady value of 16-20/min occurred almost immediately upon the removal of the fleece, or a sufficiently large part of it, and was independent

12 RESPIRATION OF SHORN SHEEP 775 of any change in the temperature of the blood supplying the brain. The depression was often accompanied by visible shivering and by a fall in ear temperature which may be evidence of a general peripheral vasoconstriction. This suggests the stimulation of peripheral receptors sensitive to the fall in skin temperature when the fleece was removed. Waites (1961, 1962) has indicated that there are relatively few warm receptors in skin which is normally covered by fleece, and that the receptors concerned in the onset of panting in the unshorn sheep are located at relatively naked areas, including the scrotum of the ram and the mammary gland of the ewe. The relation between these receptors and the environment would not be affected by shearing. It is likely, therefore, that the removal of the fleece results in the exposure of cold receptors stimulation of which gives rise to the depression of respiratory frequency, the peripheral vasoconstriction and the shivering observed in these experiments, and to the increase in metabolism reported by Graham, Wainman, Blaxter & Armstrong (1959) at temperatures below 250 C. These cold receptors must be uniformly distributed beneath the fleece. Irrespective of the location, respiratory frequency fell as the area shaved was progressively increased until % of the skin was exposed. Respiratory depression was then maximal and no further depression occurred when this shorn area was extended up to 100 %. Respiratory frequency is depressed to the same steady low value of 16-20/min when the unshorn sheep is anaesthetized with pentobarbitone or when the conscious animal is subjected to the effects of a pyrogenic agent (Bligh, unpublished observations). Possibly this represents the basic activity of the respiratory centres when deprived of external drives that are not primarily respiratory. If the effects of the removal of the fleece at 20 C were due solely to the exposure of cold receptors to a low ambient temperature, it might be expected that they would be modified when the skin temperature rose (cf. Fig. 1) and when the stimulation of cold receptors was replaced by that of warm receptors. Shivering ceased immediately upon the rise in ambient temperature, and the abrupt fall in brachiocephalic trunk temperature which often accompanied the rise in skin temperature was probably evidence of an immediate peripheral vasodilatation. But respiratory frequency remained unchanged at 16-20/min for up to 70 min after the rise in ambient temperature to 420 C. When the duration of the preliminary exposure to the lower ambient temperature was kept fairly constant at about hr, the duration of the persistent depression of respiratory frequency at 420 C increased progressively as the shorn area was increased from 25 to 100 % (Fig. 4). It also increased exponentially with the increase in the duration of the

13 776 J. BLIGH exposure at 200 C when the extent of the shaved area was held constant (Fig. 5). When the fleece of the shorn sheep was allowed to grow again, the duration of the depression of the respiratory frequency at 420 C became progressively shorter with time. At the same time respiratory frequency at the lower ambient temperature rose towards the normal level for the unshorn sheep at that temperature, although the time course of these two responses to fleece regrowth were distinctly different. It appears that the duration of the depression of the respiratory frequency after ambient temperature has been raised is a function of the intensity and duration of some effect of the lower ambient temperature upon the shorn skin surface. Possible persistent effects of the exposure of a large area of naked skin to low ambient temperatures might include a shift in deep body temperature, an abnormal thermal gradient from core to periphery, or a continued elevation of metabolism. There is no evidence to suggest any direct connexion between changes in deep body temperature and changes in the response pattern of respiratory frequency, which remained constant in duplicate experiments under prescribed conditions despite considerable variations in deep body temperature. In one experiment where the skin, subcutaneous, subscapular, and brachiocephalic trunk temperatures were all kept under continuous observation while the ambient temperature was raised there was no evidence of any relation between the periphery-to-core thermal gradient and the abrupt termination of the period of respiratory depression (Bligh, unpublished observation). Metabolic rate was not measured in any of these experiments. It may be assumed from the results of Graham et al. (1959) that metabolism was elevated when the shorn animal was exposed to the lower ambient temperature, but was no longer elevated in the sheep at 200 C ambient temperature when the fleece had re-grown to a length of 2-5 cm (Blaxter, Graham & Wainman, 1959). It was at a similar point of re-growth that the normal pattern of change of respiratory frequency was restored in the experiments reported here. It may be that both the increase in metabolism and the depression of respiratory frequency at 20 C are dependent upon the stimulation of peripheral cold-receptors, but there is no obvious causal relation between metabolic rate and the all-or-none nature of the persistent respiratory depression after the ambient temperature is raised. A persistent afferent drive from the peripheral cold receptors can be discounted. The impulse frequency from cold receptors in the tongue of the cat (Hensel & Zotterman, 1951), the skin of the cat and dog (Hensel, 1953; Hensel & Witt, 1959; Iggo, 1959) and the skin of man (Hensel & Boman, 1960) is modified immediately upon a change in the temperature of the receptor organ. In the experiments reported here the immediate cessation of shivering and inhibition of peripheral vasoconstriction when

14 RESPIRATION OF SHORN SHEEP 777 the ambient temperature was raised is interpreted as evidence of a prompt change in the impulse traffic from peripheral thermoreceptors. A peripheral disturbance to the warm receptors, delaying their response to a rise in ambient temperature, need hardly be considered. If the peripheral warm receptors are at relatively naked areas as was suggested by Bligh (1959) and demonstrated in sheep by Waites (1961, 1962) and in goats by Linzell & Bligh (1961), they would not themselves be affected by shearing. Prolonged exposure of the unshorn animal to an ambient temperature of 200 C introduces no such delay in the onset of polypnoea when the temperature is raised. It is possible that the persistent respiratory depression results from a central interference with the normal respiratory response to heat. If it is assumed that the afferent drives from both peripheral warm- and coldreceptors act upon the hypothalamic thermoregulatory centres, and that the respiratory response to these hypothalamic excitations depends upon a neural connexion between the hypothalamus and the medullary respiratory centres, it is possible that a persistent residual effect of the stimulation of peripheral cold-receptors acts either at these levels, or upon their connecting pathways, so as to block the normal responses to heat. The immediate cessation of shivering and change in peripheral vasomotor tone when ambient temperature is raised indicates that there is no general depression of central thermoregulatory control, but these two responses to the rise in ambient temperature might result from the withdrawal of the cold stimulus alone, while an increase in respiratory frequency, which is a response to heat, may require the positive influence of peripheral warm-receptors which could be selectively blocked. The observation by Waites (1962), that polypnoea could not be established by selectively heating the scrotum of the shorn ram at a low general ambient temperature is consistent with this interpretation. A model which is consistent with all the observed relations, but which does not necessarily assist their physiological interpretations, is illustrated in Fig. 7. The normal fully fleeced animal has a respiration rate of about /min at 200 C ambient temperature, and this might depend at least partially upon a mild warm receptor stimulus acting through the hypothalamus upon the respiratory centre (Fig. 7 a). The effect of removing the fleece at 200 C ambient temperature is to produce a powerful peripheral cold-receptor drive which produces a depression of respiratory frequency to a level determined by the well-established drives of the respiratory system. At the same time, it is suggested, this cold stimulus causes the build-up of some 'blocking factor' somewhere in or between the thermoregulatory and respiratory centres. The concentration or intensity of this block rises to an asymptotic level at a rate determined by the strength and

15 778 J. BLIGH duration of the cold-receptor drive (Fig. 7 b). When ambient temperature is raised to 420 C the cold receptor drive is immediately cancelled and replaced by that from the peripheral warm-receptors. This results in the Peripheral cold receptors (c) A Peripheral warm receptors (w) C B w? Ī Hypothalamic 'centres' Respiratory 'centres' C D C w C W Fig. 7. A diagrammatic representation of the postulated central block between the afferent impulses from peripheral warm receptors and the respiratory centre following the stimulation of peripheral cold receptors in the shorn or partly shorn sheep (see text). A, before ohearing; B, after shearing at 200 C ambient temperature; C, after shearing at 42 C ambient temperature following a period at the lower temperature; D, after shearing and exposure to 420 C for longer than the period of respiratory block. Abscissa of insert graphs, time; ordinate, intensity or concentration of blocking factor.

16 RESPIRATION OF SHORN SHEEP 779 immediate inhibition of shivering and peripheral vasoconstriction, but the warm-receptor drive is prevented by the 'blocking factor' from acting upon the respiratory centre. However, the intensity ofthe 'blocking factor' starts to decline towards a zero or threshold level as soon as the coldreceptor stimulus is withdrawn. The duration of this period of decline is dependent upon the level attained during the period of cold exposure, but may also be dependent upon the intensity of the warm stimulus (Bligh, unpublished observation). An absolute block to the effect of the warm stimulus upon the respiratory centre persists during this period of decline, and is then abruptly withdrawn as soon as the intensity of the 'blocking factor' falls to the zero or threshold level. Thus the concentration or intensity of the blocking factor determines only the duration of the respiratory depression after the rise in ambient temperature, and not the degree or intensity of the depression (Fig. 7 c). As soon as the 'blocking factor' has declined to the level at which its effect is withdrawn, the normal respiratory response to the warm stimulus is again permitted, and the respiratory frequency then rises abruptly to achieve the normal level of polypnoea at that particular ambient temperature (Fig. 7 d). If this model is an accurate description of the physiological events, it must follow that an abrupt reversal of the ambient conditions to the lower temperature after polypnoea had become established in the shorn animal, should result in an immediate depression of respiratory frequency to the low steady level again. This has been shown to occur. The nature of the block remains unresolved. No naturally occurring inter-neuronal block of such duration has been described, while little is known of the self re-exciting neural loops which, it has been suggested, might block the passages of impulses. However, the postulated 'blocking factor', which becomes fully effective at quite a low level of intensity, with the subsequent build-up of intensity affecting only the duration of the block, has similarities to the effects of some synapse-blocking drugs. The possibility was considered that catecholamines liberated into the blood stream in response to the stimulation of peripheral cold receptors might be involved, but the duration of the respiratory block was not affected by the continuous intravenous infusion of adrenaline or noradrenaline. The possible involvement of other substances, not necessarily appearing outside the blood-brain barrier, has still to be investigated. It is both curious and surprising that no comparable block to a thermoregulatory response has been reported amongst the countless studies of the responses of many species to both heat and cold. The long delay in the release of peripheral vasoconstriction after hypothalamic cooling in the conscious goat when this was accompanied by the additional stress of a venous puncture (Andersen, Andersson & Gale, 1962) shares the charac-

17 780 J. BLIGH teristics of a persistent 'block' and an abrupt termination, and the release of an 'endopyrogen' has been suggested as the blocking agent. In other respects, however, the two phenomena are quite different. Sweating in man upon exposure to heat is subject to a delay (Robinson, 1949) which increases with the duration of a preliminary exposure to cold (Veghte & Webb, 1961) but the delay has been attributed to a fall in deep body temperature. At present there is nothing to suggest that this block to thermal polypnoea in the shorn sheep has any general physiological application beyond the one species studied. However, it is often assumed that a delay in the thermoregulatory response to a change in ambient conditions is determined by the need for a change in the temperature of the blood supplying the brain as the primary stimulus. The possibility that any change in deep body temperature is passive, and that the delay is due to some central nervous block may be worthy of consideration. SUMMARY 1. The effect of close shearing of the fleece upon the pattern of change in respiratory frequency of the Welsh Mountain sheep during exposure to a high environmental temperature is described and analysed. 2. The immediate depression of respiratory frequency after the removal of the fleece, or a large part of it, at an ambient temperature of 200 C, is attributed to the exposure of cold-receptors uniformly distributed over the fleece-covered skin. 3. The duration of a persistent depression of respiratory frequency after shearing when the ambient temperature is raised to 420 C is shown to increase with both the time of exposure to the lower ambient temperature and the extent of the shorn area. 4. The respiratory depression at 420 C is abruptly terminated with the onset of thermal polypnoea. Respiratory frequency then rises rapidly to the normal level at that ambient temperature in the unshorn sheep. 5. The respiratory depression at 420 C, and its abrupt termination, cannot be related to the levels of skin or deep body temperature or to the gradient between them. 6. The duration of the respiratory depression is not affected by the intravenous infusion of adrenaline or noradrenaline. 7. It is suggested that the respiratory depression after the rise in ambient temperature is due to a persistent central block between peripheral warm receptors and the respiratory centres produced by, and proportional to, the duration and intensity of the preceding stimulation of peripheral cold receptors. I am indebted to Miss Mary Sheahy, S.R.N., for her assistance in the operating theatre, and to Mr A. J. Barton for his unfailing skill and perseverance as technical assistant.

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