Prem?ous researches. The previous work on C02 partial pressure in

THE CARBON DIOXIDE PARTIAL PRESSURE IN BODY CAVITIES AND TISSUE SPACES UNDER VARIOUS CONDITIONS. BY J. ARGYLL CAMPBELL. (From the Department of Applied Physiology, National Institute for Medical Research, Hampstead.) THE experiments described herein were carried out mainly to determine the effects on the C02 partial pressure in some of the tissues and body cavities, produced by changes of temperature, muscular exercise and artificial respiration. Prem?ous researches. The previous work on C02 partial pressure in tissues and body cavities is very extensive. Amongst the earliest researches are those of Davy(1) in 1823, on the C02 content in the gases in a case of pneumothorax and those of Leconte and Demarquay(2) in 1859 on the changes in C02 content in gases injected subcutaneously and into the peritoneal cavity. Attention will be directed here to some of the researches of physiological significance and of importance to the present work. In 1914 Webb, Gilbert, James and Havens(3) injected nitrogen into one side of the thoracic cavity of one monkey and a similar amount of air into one side of the thoracic cavity of another monkey of about the same size and weight, and found the C02 percentages to be 8-52 and 8-06 respectively after 48 hours. Rist and Strohl(4) concluded that there is a balance between the gases of a pneumothorax cavity and the gases in the venous blood; whilst Dautrebande and Spehl() pointed out that it was more correct to state that the composition of the gases was regulated by the blood bathing the compressed lung, this being richer in C02 than that of the normal lung, because of the lessened circulation due to the compression. Grass and Meiners(6) distinguished between an open and closed pneumothorax by drawing out some of the gas from the cavity. If there was an opening elsewhere communicating with the air, fresh air rushed in and thus lowered the C02 percentage. They also described a method to estimate the volume of gases in the thoracic cavity. Henderson and Haggard(7) injected air into the abdominal cavity of dogs under local anaesthesia and showed that the C02 tension in the abdominal air approximated in about one hour, to that in the arterial

274 J. A. CAMPBELL. blood or in the alveolar air. They also found that injection of HCI lowered the C02 tension in the abdominal air just as it did in the arterial blood. Recently two papers have been published dealing with the CO2 tension in the stomach cavity. Edkins(8) found that after injecting nitrogen or a mixture of nitrogen and oxygen into the stomach of a cat, the C02 tension was above the C02 tension in alveolar air but often not very much higher. Dunn and Thompson(9) studied the CO2 tension in the stomach of man and concluded that percentages as high as 9 were possible in normal subjects. Strassburg (10) found that the C02 pressure was 7*7 p.c. in a loop of the small intestine in which air had been placed. He also examined the C02 tension in bile and in urine and found it to vary between 7 and 9 p.c. Ewald(u) found that pathological fluids may contain 11x5 p.c. C02. Methods. Air was injected into the thoracic cavity, the abdominal cavity, the stomach, the intestine, the bladder and under the skin of the face, of the body and of the limbs. In most cases an ordinary hypodermic needle was used for the injection. Glass cannulae were tied into the stomach, intestine, and sometimes into the abdominal and thoracic cavities. The stomach and the intestine were in most cases washed out with recently boiled normal saline. A few observations were made with the usual contents present. Urethane was used when a general an8esthetic was necessary. A catheter was passed into the bladder and clips were adjusted so that the air could not escape by the urethra. In the case of the skin experiments, no anaesthetic was required. The amount of air injected was never so great as to cause a high mechanical pressure. The sense of touch was employed to estimate this pressure. The alveolar C02 partial pressure was estimated sometimes by the Higgins-Plesch method as used by Henderson and Haggard(7) and sometimes a catheter was passed into a bronchus. The latter method required an anaesthetic. In the former method a rubber mask was fixed over the nose and mouth of the animal which rebreathed a quantity of air (25-50 c.c.) for 30, 40 and 50 seconds from a small rubber bag. The rebreathed air was never in this bag for more than about 60 seconds and control tests showed that there was no appreciable leakage of CO2 through the rubber in this time. The C02 analyses were carried out with the Haldane apparatus, about 10 c.c. of gas being analysed. Results in general. Many of the results of previous observers were confirmed. It was found that the C02 tension rose rapidly in a few minutes after the injection of air and usually reached equilibrium in from 30 to 60 minutes. As Henderson and Haggard(7) observed it

CARBON DIOXIDE IN TISSUE SPACES. 275 was found that the presence of a large quantity of fat greatly slowed down the rate with which the C02 tension reached equilibrium. In most cases the C02 partial pressure in any of the situations examined in the normal resting animal approximated to that in the alveolar air; nevertheless there were occasions on which fairly marked differences were obtained between C02 tensions in the alveolar air and in different cavities and tissues. Usually the relative changes in C02 tension were similar in the different parts of the body examined, even when absolute values showed little agreement. Experimental acidosis. Henderson and Haggard(7) showed that the C02 partial pressure in abdominal air falls after the intravenous injection of HCI. A similar experiment was done with air injected under the skin of a rabbit (see Table I). The alveolar C02 tension (Higgins- Plesch) and the tension in the air under the skin fell 5 mm. Hg after the intravenous injection of N/4 HCI. Effect of temperature. It was observed that exposure to a warm atmosphere greatly increased the C02 partial pressure in air under the skin and in the abdominal cavity of a rabbit although the rectal temperature was often not greatly altered. Subsequent exposure to a cooler atmosphere reduced the pressure again, sometimes only after several hours but usually in an hour or two. Tables II to V illustrate examples of such experiments. In Table II figures are also given for the C02 tension in the large intestine containing its usual contents of semidigested food; the pressure therein was found to be as high as 113 mm. although, in this case, the air was not shut in by ligatures. Table III records the alveolar C02 tension as estimated by the catheter method whilst Table IV shows the results using the Higgins-Plesch method. In Table V, the C02 tension in air in the abdominal cavity is compared with that in air under the skin. It will be noted that in some respects there were differences between the tensions in these situations although exposure to a warm atmosphere produced a rise of tension in both cases. In addition to the temperature, figures are also given in the Tables II to V for the cooling power as estimated, in millicalories per sq. cm. per sec., by L. Hill's dry katathermometer. An experiment was done in which the hind limbs and pelvis of a rabbit were placed in a warm bath at 370 C. whilst the fore limbs and shoulders were covered with cold poultices at 150 C. The C02 tension under the skin which was warmed was similar to that under the skin which was cooled, so that the marked effect obtained by exposing the animal to a warm atmosphere may have been due to an effect on the

276 J. A. CAMPBELL. body in general, such as an increase of metabolism accompanied by a diminished excretion of C02. General heating may have dilated the capillaries and brought far more blood to the skin so that the circulation time of the blood was prolonged. Food did not produce any appreciable change in the CO2 partial pressure under the skin of a cat. Effect of exercise. Table VI records results showing that exercise for 18 minutes markedly increased the C02 partial pressure under the skin in the case of a rabbit although the body temperature was not altered greatly. Other experiments with rabbits showed similar results. In Table VII results are given which were obtained from a kitten. Exposure to a warm atmosphere and two periods of ten minutes mild exercise increased the 002 tension under the skin from 40 mm. to 48 mm.; subsequent rest in a cooler room reduced the tension to 40 mm. The author hopes to carry out similar experiments on man during exercise and exposure to heat. Effect of artificial respiration. Artificial respiration was performed under urethane by means of Schuster's(12) double-action pump, made for Dale and Evans(13). The C02 partial pressure under the skin before artificial respiration was commenced, in the experiment illustrated in Table VIII, was about 50 mm.; such high figures were sometimes observed with the animal under an ancesthetic. After 21 minutes of artificial respiration the tension fell to 37 mm. but was not altered much by a further 60 minutes of artificial respiration. Except for a few short interruptions, the artificial respiration was continuous. About 22 c.c. of air were pumped into and withdrawn from the lungs 190 times a minute. After cessation of artificial respiration the CO2 tension rose again and reached 54 mm. In this experiment the respiratory quotient was 0-6 during artificial respiration, so that the lung was probably not completely opened up by the pumping in and out of 22 c.c. of air. In an experiment on a cat (see Table IX) the amount of air pumped into the lungs was much greater and the C02 tension under the skin fell as low as 21 mm. In this experiment the respiratory quotient was above 1. Many other experiments, in some of which air was injected into the abdominal cavity, gave similar results1. The blood pressure was recorded in some of these 1 Further experiments, carried out by the author in Dr Dale's laboratory, have shown that the 02 consumption was increased by this method of artificial respiration. This may have been due in part to an attempt by the tissues to replace CO. It was very likely due in part to alkalosis since the author has recently found that intravenous injection of NaHCO, in urethanised cats caused a definite increase in 02 consumption, whilst intravenous injection of HCI produced the opposite effect. The latter phenomena -probably constitute a general physiological principle.

CARBON DIOXIDE IN TISSUE SPACES. 277 experiments and the author hopes to publish the results in the near future. C02 partial pressure in the tissues and cavities just before and some hours after death. When an animal was dying the C02 tension often rose above 80 mm. just before death. Tables I, II, V and VIII record the high results obtained some hours after death, 193 mm. being obtained in one case. SUMMARY. 1. Injection of air under the skin afforded a ready means to examine changes in C02 partial pressure within the body. No anesthetic was required and the animal was able to move about normally. 2. Intravenous injection of acid reduced the C02 partial pressure in air under the skin. 3. Exposure to a warm atmosphere (370 C.) greatly increased the C02 partial pressure in air under the skin and in the abdominal cavity, although the body temperature was not greatly altered. 4. Exercise markedly increased the C02 partial pressure in air under the skin, although the exercise produced only a slight rise of body temperature. 5. Artificial respiration greatly reduced the C02 tension in air under the skin and in the abdominal cavity, figures as low as 21 mm. being recorded. The author is much indebted to Dr Dale for the loan of the doubleaction pump and to Dr Leonard Hill for kindly criticism in the above research. REFERENCES. (1) Davy. Phil. Trans. p. 496. 1823. (2) Leconte and Demarquay. Arch. gen. de med. (5), 14, pp. 11X, 424, 545. 1859. (3) Webb, Gilbert, James and Havens. Arch. Int. Med. 14, p. 883. 1914. (4) Rist and Strohl. Annals de Med. 8, p. 233. 1920. (5) Dautrebande and Spehl. Compt. Rend. 86, p. 970. 1922. (6) Grass and Meiners. Beit. zur klin. Tuberk. 51, p. 134. 1922. (7) Henderson and Haggard. J. Biol. Chem. 38, p. 71. 1919. (8) Edkins. J. Physiol. 56, p. 421. 1922. (9) Dunn and Thompson. Arch. Int. Med. 31, p. 1. 1923. (10) Strassburg. Arch. ges. Physiol. 6, p. 94. 1872. (11) Ewald. Arch. f. Anat. Physiol. u. wiss. Med. 663, 1873; 422, 1876. (12) Schuster. J. Physiol. 56. 1922. Proc. Physiol. Soc. x. (13) Dale and Evans. Ibid. p. 125. 1922.

278 J. A. CAMPBELL. Appendix. TABLE I. Rabbit; no anasthetic. C02 mm. Alveolar air Under mins. Conditions (mask) skin 0 450 c.c. air injected under the skin 130 40 215 40 226-40 232 10 c.c. N/4 HCI into vein of ear 275-35 282 10 c.c. N/4 HCI into vein of ear 304-35 - 310 - - 35 372-35 382 37-17 hours after death 137 TABLE II. Rabbit; urethane. 350 c.c. air injected under skin. 200 c.c. air injected into large intestine. C02 mm. Temp. Dry Large Under mins. C. kata. intestine skin 01 16-0 6-1 - 120 111 46 130 37-0 0.0 230 113 64 250 16-0 6*1 343, 84 54 1 Air injected into large intestine and under skin. TABLE III. Rabbit; urethane. 350 c.c. air injected under skin 24 hours previously. Rectal Alveolar Temp. Dry Temp. air Under mins. C. kata. C. (catheter) skin 0 13*5 9*7 370 44 45 19 37.0 0.0 129, 37*5 46 53 201 38&0 53 59 216 13-5 9.7. - 286 37T0 51 57 350, - 49 17 hrs. after 187 death TABLE IV. Rabbit; no anesthetic. 250 c.c. air injected under skin 17 hours previously. C0 mm. Alveolar Temp. Dry air Under mins. 0C. kata. (mask) skin 0 18-0 6-5 40 40 2 37*0 00-122 49 64 144 6-0 11*4-216 36 64 276 36

CARBON DIOXIDE IN TISSUE SPACES. 279 TABLE V. Rabbit; urethane. 250 c.c. air injected under skin. 200 c.c. air injected into abdominal cavity. mins. 01 70 83 222 234 319 17 hrs. after death Temp. 0 C. 18-0 37*0 18-0 9 Dry kata. 6-0 0.0 6-0 i Abdominal Under cavity skin 38 44 50 41-193 1 Air injected under skin and into abdominal cavity. 59 62 TABLE VI. Rabbit; no anaesthetic. 300 c.c. air injected under skin 48 hours previously. rime Conditions Rectal under rnins. T. 0 C. skin 0 At rest 390 42 4 to 22 Muscular exercise 23 At rest 39-2 76 139 38-7 44 mins. 0 60 80 91-101 102 130 250 264-274 275 285 370 TABLE VII. Kitten; no ansesthetic. Dry under kata. skin 6-3 - Temp. Conditions C. 200 c.c. air in- 15-0 jected under skin Ten minutes mild exercise Rest In hot room Ten minutes mild exercise Rest In cool room 14-5,37-0 ) 40 lp 41 9.1 _ 0.0 44 46 9 48 15.0 6-3,%, 40 TABLE VIII. Rabbit; urethane. under mins. Conditions skin 0 250 c.c. air injected - under skin 60 50 93-51 100 Artificial respiration; 190 per min.; 22 c.c. 121 37 172 38 203 39 211 Artificial respiration stopped 261 Normal breathing 43 293 54 17 hours after death 150 mins. 0 60 103 128 148 212 253 255 290 310 TABLE IX. Conditions 400 c.c. air injected under skin Artificial respiration Artificial respiration stopped Shallow breathing Animal died Cat; urethane. Vol. at each stroke c.c. Strokes per min. under skin 26 180-33 46 190-200 -,18 26 104 180- pi,. 21 - - 33