(From the Physiotogicat Laboratory, Cambridge.)

Transcription

1 THE OXYGEN EXCHANGE OF THE SUPRARENAL GLAND. BY K. 0. NEUMAN. (From the Physiotogicat Laboratory, Cambridge.) THIS paper deals with the question of the amount of oxygen taken in by a unit weight of the suprarenal gland in a unit of time. The venous blood flowing out of the gland was compared, as regards its oxygen content, with an equal amount of arterial blood, collected at the same time. The Barcroft-Roberts differential blood-gas apparatus(i) was used. The experiments were chiefly made on cats, but a few were made on rabbits. The animals were first anasthetised with chloroform in the case of cats, and with ether in the case of rabbits; urethane was then injected and A.C.E. mixture given as required by a tracheal tube. The abdominal viscera were removed with the exception of the suprarenals, the kidneys and the liver, the arteries being first tied, the blood pressed out of the organs and then the v. portee and ductus choledochus tied. A cannula was tied into an artery to collect samples of arterial blood, usually the aorta abdominalis at the level of the kidneys. To collect samples of the blood from the suiprarenal gland it is best to insert the cannula into the v. cava or v. renalis as close to the v. suprarenalis as possible, the suprarenal vein itself being too small in the cat or rabbit. As a rule it is advisable to collect the blood only of the left suprarenal body, which is clearly visible after the removal of the intestine. The right gland is almost always hidden and attached to the v. cava by connective tissue. If, as sometimes happens, the vv. suprarenales join the v. cava at almost the same level, it is necessary to collect the blood of both glands together. In cats the left suprarenal vein will be found in the majority of cases to join the v. cava directly, while in others it joins the renal vein. In the first case it is best to tie the cannula into the v. cava, in the second into the renal vein. Tihe left suprarenal vein, which passes over the ventral side of the gland, is a continuation of two or three smaller veins which come from the muscles of the back (v. lumbalis). These must be ligatured close to the organ.

2 OXYGEN EXCHANGE OF SUPRARENAL. Almost immediately after tying, the colour of the blood as seen through the wall of the suprarenal vein becomes much redder. According to the anatomical condition of the animal either the v. cava just above the suprarenal vein, or the renal vein medial of the suprarenal vein is tied and the blood of the gland is thus forced into the cannula mentioned above and a horizontally placed pipette joined to the cannula. The pipette is graduated into tenths of a c.c., its internal surface moistened immediately before use with a freshly prepared solution of hirudin. It has proved to be better to divert the blood into the cannula by tying than by clamping the vena cava or the renal vein. The samples of arterial blood are best collected simultaneously with the venous blood. After the blood was analysed, I made sure by injecting and dissecting that the venous blood collected only came from the suprarenal gland. This organ was then cut out and weighed. An attempt to determine the oxygen consumption of the suprarenal gland, tut paying no regard to rate of blood-flow and weight of the organ, was made several years ago by Langlois and Chassevant(2). These authors compared the blood flowing out of the suprarenal gland with that of the femoral vein and drew the conclusion that, since the venous blood contains relatively large quantities of oxygen, the gland uses a small quantity of oxygen only. The present investigation confirms the general trend of their analysis, but shows their deduction to be entirely fallacious. A summary of the first experiments I did on this subject was given in a previous communication (3). The mean values given there were lower than those in later experiments, with regard both to the rate of bloodflow and to the amouint of oxygen used by the organ per gram and minute. This results from greater care in the later experiments in maintaining a good blood-pressure and in keeping the suprarenal as nearly as possible at the body temperature throughouit the whole % operation. The following are my more recent determinations of the " coefficient of oxidation "-to use the phrase of Chauveau and Kauffmann-of the suprarenial bodies: Oxygen used per gram per min.: i. Cats (successive experiments):.05 *03 *036 *04 *04 *03 { *048 Mean -045 c.c. per gm. per min. *045 j 05 ii. Rabbits (successive experiments): {034 *06 05 Mean *044 c.c. per gm. per min. 189

3 190 K. 0. NEUMAN. The coefficient is greater than that of any resting organ which has yet been accurately investigated, thus for the submaxillary gland it is about '02, for the kidney about 6 and for the liver 8 or less. It must be noticed that when duplicate determinations were made the results above - differed only by about 8 0/0. In this connection Fig. 1. Exp. 2. The upper line shows the arterial blood-pressure, the middle line shows the blood-flow through the suprarenal gland, each c.c. being marked by an electric signal. Time in seconds. we may also cite the following four determinations of the coefficient of oxidation in other, though not normal, animals, in one '11, '12, '12, in another '07 and '05. There is no greater error than can be accounted for by the necessary errors of gas analysis. The degree of error depends upon the difference of pressure in the apparatus. This varied in different experiments. I have in each case calculated from the difference of pressure the limits of experimental error and give them in the Tables.

4 OXYGEN EXCHANGE OF SUPRARENVAL. 191 Large as is the coefficient of oxidation I have been able to raise it materially by the intravenous injection of adrenalin. Each injection of adrenalin caused a rise in the oxygen consumption. In some cases two samples were taken during the rise of pressure caused by the adrenalin. In Exp. 6, in which the secon(l sample was taken inmmediately before and whilst the injection was made, the increased mietabolism was only apparent in the third. No doubt this was partly due to the fact that some of the blood in the second sample was that contained in the dead space, as the collection of this sample was started 3 sec. before the injection of adrenalin. In Fig. 1 I have an illustrative tracing taken from Exp. 2: i. is the tracing during sample a, ii. that during samples b and c and iii. that during sample d. TABLE I. Exp. Animal 1 Rabbit and were taken adrenalin. 2 Cat Weight of Limits of exsuprarenals Rate of blood-flow Oxygen used periniental error, in grams per gram and minute of organ c.c.pergram&min. Left *22 (a) 4'19 c.c. 6'99 '06 c.c. ' (d) 3'54 during the rise of pressure caused by injecting Left '32 (a) (d) '04 5'95 3'02 '04 '05 '05 '03 and were taken during the pressor effect of '1 mg. adrenalin. 3 Cat Left '25 (a) (a) taken before injection of '1 mg. adrenalin, at the beginning of the fall of pressure. 4 Cat Left '268 (a) (d) 4' '21 at the '64 8'18 '03 *02 *1 mg. of '02 *008 '03 '18 beginning of the plateau, '04 '18 '02 '03 '005 '04 '008 *1 mg. adrenalin was injected between (a) and and between and (d). 5 Cat Left '225 (a) (d) (e) (f) ' '046 '045 '068 '181 '167 '070 *015 '02 5 7

5 192 K. 0. NEUMAN. 1 mg. adrenalin was injected 2 mins. 14 secs. after sample was taken, 12 secs. later the collection of sample was started, between taking sample and sample (d) there was an interval of 1 min. 35 secs., 2 mins. 26 sees. after sample (d).1 mg. adrenalin was injected again, sample (e) taken during the plateau and 4 mins. 6 sees. later -1 mg. adrenalin more injected and sample (f) taken during the pressor effect. The arterial blood-pressure was about 115 mm. Hg during taking samples (a) and, about 132 mm. at sample, which was taken during the rise produced by adrenalin, about 100 mm. at sample (d) during the fall, 134 mm. at sample (e), taken during the plateau of the second injection of adrenalin, and about 100 mm. during taking sample (f) after a third injection of adrenalin. 6 Cat Left *264 (a) 6-87 *048 * * * (d) (e) (f) 8: * *009 was started to take 3 secs. mg. injected 1 min. 56 sees. after after Sample adrenalin was before taking the sample injection (a) and of adrenalin. 2 mins. 10 sees..1 sample (d). The arterial blood-pressure was about 130 mm. Hg whilst sample (a) was taken, about 180 mm. during samples and (d), and 72 mm. during sample (f). 7 Cat Left *133 (a) *05 * *02.1 mg. adrenalin was injected after sample. The blood-pressure was about 136 mm. Hg at the beginning of taking sample (a), 110 mm. at taking sample. Samples taken at 12.46, and 1.35 p.m. 8 Cat Both -405 (a) *02 103a mg. adrenalin was injected after sample (a). Samples taken at 5.35 and 5.39 p.m. 9 Cat Left *2 (a) (d) 9-83 *066 * *245 *080 *01 *015 *03 * (e) mg. adrenalin was injected after sample. Blood-pressure about 130 mm. Hg at taking sample (a), 88 mm. at taking sample (e). It will be seen from the Table that the oxygen use was increased by injecting adrenalin. The coefficient was in one case above '2, in two cases above *15 and in six cases above 1 c.c. per gram per min. The slight increase in the rate of blood-flow was accompanied by a marked increase in metabolism. In Exps. 3, 5, 6, 7 the rate of blood-flow corresponded to the general arterial pressure, and was but slightly increased or was even slower after adrenalin was injected although the oxygen use was considerably increased; it is obvious that in these

6 OXYGEN EXCHANGE OF SUPRARENAL. experiments increase in the blood-flow was not the cause of the increased metabolism, and we may infer that in the experiments in which the blood-flow was markedly increased, its effect on metabolism was only a subsidiary one. The organ which approaches the nearest to the suprarenal, as regards the blood supply, is the thyroid gland with over 5 c.c. of blood per gram per min. according to Tschuewsky(4). Exp. 7 was performed specially with the object of testing the point mentioned above. After the normal sample was taken the aniimal was bled to the extent necessary to make the rate of flow during the adrenalin-sample less than during the normal samples, nevertheless the oxidation was increased. It would seem therefore that adrenalin produces a specific increase in the metabolism of the suprarenal gland. In Exp. 7 the rate of blood-flow and the coefficient of oxidation were considerably greater than that which occurred in the other experiments (cf. Table I). A similar result was obtained in Limits of ex- Weight of supra- Rate of blood-flow Oxygen used perimental error, Animal renals in grams per gram and minute of organ c.c. per gram&min. Exp. 10 Cat Left *2, (a) 9-18 c.c. *11 c.c *12 ' *12 03 Blood-pressure about 130 mm. whilst taking the samples. 193 Both of these animals were in an advanced stage of pregnancy, and it is possible that the greater metabolism was due to this state. Kolmer(5 has described histological changes in the suprarenals of the gravid guinea-pig. In general it may be said that an arterial blood-pressure of 130 mg. Hg was accompanied by a blood-flow through the gland of 6 to 7 c.c. per gram of organ per minute. I may note that in nmy early experiments in which the rate of blood-flow through the gland was sub-normal, there was a rough correspondence between the rate of blood-flow and the oxygen use, indicating that in these circumstances this former does increase the latter. The effect might be produced either by a direct action or by an increase in the temperature of the gland, which on account of its superficial position has a tendency to become cooled. The experiments are given in Table II, and are arranged in the order of rate of blood-flow. In Exp. F, the rate of blood-flow is very low, the oxygen consumption diminished, but still quite considerable, which seems to point to a certain degree of activity of the gland.

7 194 K. 0. NEUMAN. Biedl(6) found that the injection of suprarenal extract in the dog caused a primary increase of the blood-flow through the suprarenal gland and then a decrease. He considered that this showed the presence of vaso-constrictor nerve fibres in the gland. As will be seen from the data given in Tables I and II I have found no satisfactory evidence of vasoconstriction. TABLE II. Weight of Limits of suprarenals Rate of blood-flow Oxygen used experimental error 1Exp. Animal in grams. per gram and minute of organ c.c.pergm.permin. A Cat Left c.c. 05 c.c. *01 B Cat Left *036 *01 C Cat Left D Rabbit Both -355 (a) * E Cat Left In the preceding experiments the arterial blood-pressure varied from about 70 to 100 mm. Hg, in the following it was about 40 to 45 mm. F Cat Both In order to compare the rate of blood-flow and oxygen use in the kidney with that of the suprarenal gland, the following experiments were made. Exp. 11. Cat. Weight of left kidney 21-7 grs. Rate of blood-flow Oxygen used Limits of experimental error per gram and minute of organ c.c. per gram and min. (a) 1-5 c.c. -06 c.c Sample was taken during tbe rise of blood-pressure produced by -1 mg. of adrenalin. The blood-pressure and the amount of blood-flow through the kidney before, during, and after adrenalin are shown in Fig. 2. It will be seen from the Table that in the kidney the decreased bloodflow caused by adrenalin was accompanied by a large decrease in the oxygen use. In the following experiment observations were made simultaneously on the suprarenal gland and the kidney. Exp. 12. Rabbit. Blood taken from left suprarenal and right kidney. Weight of suprarenal -3 gr., and of kidney 6-2 grs. Rate of blood-flow Oxygen used Limits of experimental error per gram and minute of organ c.c. per gram and mis. (a) Suprarenal 1-16 c.c. -05 c.c Kidney Suprarenal (d) Kidney mg. adrenaln was injected after.

8 OXYGEN EXCHANGE OF SUPRARENAL. 195 In this experiment the injection of adrenalin was followed by increased blood-flow and increased oxygen use as in the suprarenal body, whilst there was decreased blood-flow and decreased oxygen use in the kidney. Fig. 2. Exp. 11. The upper line shows the arterial blood-pressure, the middle line shows the blood-flow through the kidney, each c.c. being marked by an electric signal. Time in seconds. SUMMARY. 1. The suprarenal gland has a remarkably rich supply of blood, which varies of course with the general blood-pressure. To a pressure of 130 mm. of mercury corresponds an amount of 6 to 7 c.c. of blood per gram and minute of gland. This is, so far as known, the highest figure of blood-supply for any normal organ; the nearest being the thyroid gland with over 5 c.c. per gram and minute of organ. 2. The blood-flow through the gland during the pressor effect of adrenalin is slightly increased. 3. The suprarenal body has an oxygen-consumption of about 045 c.c. per gram and minute of organ. 4. During the rise of blood-pressure caused by adrenalin the suprarenal body shows an increase of the oxygen consumption, the amount of oxygen used being sometimes raised more than threefold. The oxygen consumption of the kiduey in simultaneous and control experiments is greatly diminished during the high blood-pressure produced by injection of adrenalin. I wish to express my sincerest thanks to Pro Langley for allowing me to work in the Cambridge Physiological Laboratory as well as for his

9 196 K. 0. NEUMAN. kind advice and criticism. I have much pleasure also in thanking Mr Barcroft for the invaluable help he has given me throughout the work, as well as for instruction in method and for the performance of several of the blood-gas analyses. REFERENCES. (1) Barcroft and Roberts. This Journal, xxxix. p (2) Barcroft. Ergebn. d. Physiol. vii. p (3) Neuman, K. 0. This Journal, X2LIII. Proc. Phyrsiol. Soc. p. xxxi (4) Tachuewsky, J. A. Pfliger's Arch. xcvii. p (5) Kolmer, W. Ibid. cxiv. p (6) Biedl, A. Ibid. LxvII. p