-~~ -v GAS TENSIONS IN THE MUCOUS MEMBRANE OF THE STOMACH AND SMALL INTESTINE. By J. ARGYLL CAMPBELL. From the National Institute for Medical Research, Hampstead. (With six figures in the text.) (Received for publication 12th May 1932.) THE literature on this subject, which was reviewed recently (CAMPBELL, 1931), indicated that the results obtained were neither extensive nor conclusive; it was for these reasons that the present observations were undertaken. METHODS. The animals (cats, rabbits, dogs) were anaesthetised with the usual doses of amytal, and in addition received A.C.E. mixture during the operations. The abdomen was opened, and in some experiments the stomach was washed out with warm saline solution (37 to 39 C.). Ligatures were tied round the cardiac and pyloric orifices, avoiding injury to the blood-vessels and nerves. A moderate amount (5 to 1 c.c.) of a mixture of oxygen and nitrogen (mainly) was injected into the stomach cavity and left there for several hours. In other experiments a loop (2 to 3 cm.) of the small intestine was similarly prepared and about 1 to 15 c.c. of the gas mixture was confined within the lumen either by ligatures or by spring clips, care being taken to avoid twisting the loop. Samples of gas (2 to 1 c.c.) were drawn off at intervals into gas sample-tubes through a fine hypodermic needle filled with mercury and thrust through the wall of the viscus. The abdomen of the animal was usually kept under saline at 37 to 39 C. to exclude air from the peritoneal cavity. In the few experiments, when air was not thus specially excluded from the abdominal cavity, no significant difference was observed in the results. The incision in the abdominal wall was kept closed in all cases by ligatures except when samples were being withdrawn. Gas analyses were carried out in the large or small Haldane apparatus; allowance for water vapour has been made in the results. In some of the gas mixtures injected the oxygen tensions were higher than those existing in the mucous membrane, and in others lower; by thus approaching equilibrium both from a higher and a lower level the normal limits for these tensions in the mucous membrane were ascertained. The tensions at equilibrium level are evidently the
16 Argyll Campbell same as those existing in the cell-lining of the mucous membrane, since diffusion of gases takes place through these cells. EFFECTS OF ANAESTHETICS UPON TISSUE GAS TENSIONS. Since the animals must obviously be deeply under the influence of the anaesthetic in such experiments, it is necessary to determine the TABLE. GAS TENSIONS BEFORE AND AFTER AN.ESTHETICS. 2 tensions, mm. Hg. CO2 tensions, mm. Hg. Animal. Anaesthetic. Skin. Abd. cav. Skin. Abd. cav. Before. After. Before.* After. Before. After. Before. After. Ca Cat R b 1 Cat Amytal 1,, Urethane Ether Chloroform,,l 29 19 32 (25)* 24 (22) 25 24 28 (24) 15 25 (2) 24 24 (24) 13 28 18 (2) 17 24 (2) 17 22 17 16 (19) 14 18 26 (22) 22 () 36 35 39 (39) 34 37 (35) 4 39 39 39 (39) 34 38 42 (4) 31 43 3 3 39 (35) 32 34 (33) 39 4 33 38 3 (36) 31 38 43 () 25 42 49 () 44 () 5 51 49 (49) 53 (49) 51 52 (52) 44 56 54 (5) 59 (53) 57 6 52 (5) 61 6 5 (55) 51 57 (54) 42 () () 5 () () 5 1.. 53 49 (49) 5 () 42 61 49 (49) 55 5 43 () * Figures in brackets are averages. effect, if any, of such anaesthetics upon tissue gas tensions. Previous observers had not paid sufficient attention to this point. I have therefore estimated the oxygen and carbon-dioxide tensions under the skin and in the abdominal cavity immediately before and a few hours after administration of the usual anaesthetics (see table). The tensions in normal animals before anaesthesia are reasonably constant for any individual animal, and do not change appreciably from hour to hour under normal conditions (CAMPBELL, 1924, 1926). The results in the
---,,-*...-------.. Gas Tensions in Mucous Membrane of Stomach and Small Intestine 161 table indicate that, although occasionally the tensions may not be greatly changed by the usual doses of amytal and urethane, the average effect of these aneesthetics is a fall of oxygen tension of about 4 mm. Hg and a similar rise of carbon-dioxide tension. With urethane, individual animals may show a fall of oxygen tension of 12 mm. Hg and a rise of 16 mm. Hg in carbon-dioxide tension. Chloroform, as used for a short operation (3 to 6 mins.), also tends to lower oxygen tensions, whilst ether produces no change or a slight rise in this tension. Allowance for such changes must therefore be made in experiments dealing with the present problem. The total average effect of the ansesthetics employed in the present research is taken to be a fall of oxygen tension of about 4 mm. Hg and a rise of carbon-dioxide tension of the same degree. GAS TENSIONS IN THE MuCous MEMBRANE OF THE STOMACH. The tensions in the gas mixtures injected are indicated at zero hour on the charts. The tension changes at about hourly intervals up to 4 t 3 2 o\ -O 1 1 2 3 4 hours. The marks on the abscissa represent hours. 2 tension in mm. Hg on ordinate. * Cats. s. FiG. 1. the 4th or 5th hour are plotted out, thus illustrating the approach towards equilibrium. I have drawn straight lines instead of curves because the results for the different experiments are better distinguished from one another. In the case of carbon dioxide, which diffuses out rapidly from the mucous membrane, the true curve rises very steeply from zero, indeed more suddenly than represented in any of the charts. This point, however, is not considered at present, the main purpose of the charts being to demonstrate when equilibrium between the gas tensions in the lumen and in the mucous membrane becomes established. This occurs, of course, when the lines in the charts become horizontal.
162 Argyll Campbell The results for oxygen tension in the mucous membrane of the stomach of cats and rabbits are shown in fig. 1. The limits for the 8 -^6 -_. -O II. - 2 E-- I I.r- I 1 2 FIG. 2. 3 4 hours. 7 F p, 6-11 z 5 cl 4 O] 11 4 j I p.1.1 4 I -o z 3 *- 2 EH 1 - III S 1. I,'. - III I,I II I- 3 hours. FIG. 3. different animals are 7 to 18 mm. Hg; or, correcting for effects of anaesthetics, about 1 to 2 mm. Hg. Mrs EDKINS' (1922) results for oxygen tension in the cat's stomach are given in fig. 3 (continuous lines)
Gas Tensions in Mucous Membrane of Stomach and Small Intestine 163 and suggest about 1 mm. Hg, but she has not made any allowance for effects of anwesthetics-namely, urethane and either ether or chloroform. Fig. 2 gives my results for carbon-dioxide tensions in the mucous 1 xo 1 ali 11 w bo In 6 In Ca.4 v U, U,.S bo c,q v ) to *2H- *=au n u m uolqueal go Co C uxu* i uomsual go membrane of the stomach, the normal limits being apparently between 4 and 6 mm. Hg. The figure above 6 is probably due to the occasional marked effect of anesthesia. Mrs EDKINS' results for carbondioxide tension are shown as circles in fig. 3. It is not possible from the results she has given to insert more points, although she had evidently determined that equilibrium had become established. Her highest figures are probably due to the added effects of anaesthesia.
164 Argyll Campbell DUNN and THOMPSON (19) give 6 mm. Hg as the maximum tension for carbon dioxide in the normal stomach of man. M'IVER and his co-workers (1926) in a research for other purposes -namely, to determine the rate of exchange of different gases through the mucous membrane of the alimentary canal-have recorded one 15 a 125 11 1 11 bl 75 1-5 25 1 2 3 4 5 6 iours. FIG. 6. observation which gives results for gas tensions in the stomach similar to those stated above. TENSIONS IN THE MUCOUS MEMBRANE OF THE SMALL INTESTINE. I found that the normal limits for oxygen tensions in the mucous membrane of the small intestine of cats and rabbits are between 2 and 4 mm. Hg (fig. 4) after correcting for effects of ana_sthesia. A dog gave somewhat higher figures-namely, mm. Hg. M'IvER and others (1926) give some statistics which are in general agreement with the above. I have charted these in fig. 6 (continuous lines), and it is not possible to give more than one point for each of their experiments; but it is obvious from the observations on different animals that the oxygen tension lies somewhere between 25 and 5 mm. Hg when correction is made in their results for effects of anaesthetics. My own observations on carbon-dioxide tensions are recorded in fig. 5, the normal limits lying between 35 and 6 mm. Hg; as in the case of the stomach, the highest figures are probably from animals in
Gas Tensions in Mucous Membrane of Stomach and Small Intestine 165 which aneesthetics produce profound changes in this tension. M'IvER and co-workers' (1926) results, recorded as circles in fig. 6, indicate a carbon-dioxide tension of about 35 mm. Hg. These observers report some observations which give information regarding gas tensions in the small intestine following injection of pure hydrogen and pure methane; the oxygen tension seems to be about 63 mm. Hg, but in one experiment with hydrogen this tension was as high as that for oxygen in arterial blood-namely, about 1 mm. Hg; this observation requires confirmation. However, I have obtained (CAMPBELL, 1925) an oxygen tension in the subcutaneous tissues as high as 7 mm. Hg during dilatation of vessels, so that the high figures just mentioned are probably due to increased circulation caused by the pure hydrogen and methane, which are not normally present anywhere in the tissues at such high tensions except in the lumen of the large intestine when food is undergoing fermentation. It is for this reason that when such investigations are undertaken the gases and their tensions in the mixtures injected should show some resemblance to those normally present in the tissues; in this way the tissues will not be abnormally exposed. SUMMARY. 1. The normal oxygen tension in the mucous membrane of the stomach of the cat and rabbit is about 1 to 2 mm. Hg, while the carbon-dioxide tension is about 4 to 6 mm. Hg. 2. The normal oxygen tension in the mucous membrane of the small intestine of the cat and rabbit is about 2 to 4 mm. Hg; that for the dog may be slightly higher. The carbon-dioxide tension is 35 to 6 mm. Hg. 3. Anawsthetics, particularly urethane and amytal, may cause a rise of carbon-dioxide tension and a fall of oxygen tension in the tissues, the average change being about 4 mm. Hg in each case. Individual animals may show much more marked effects than these. REFERENCES. CAMPBELL, J. ARGYLL, Journ. Physiol., 1924, lix. 1. CAMPBELL, J. ARGYLL, ibid., 1925, lix. 399. CAMPBELL, J. ARGYLL, ibid., 1926, lxi. 2. CAMPBELL, J. ARGYLL, Physiol. Reviews, 1931, xi. 1. DuNN, A. D., and W. THOMPSON, Arch. Int. Med., 19, xxxi. 1. EDKINS, NORA, Journ. Physiol., 1922, lvi. 4. M'IVER, M. A., REDFIELD, A. C., and E. B. BENEDICT, Amer. Journ. Physiol., 1926, lxxvi. 92. VOL. XXII., NO. 2.-1932 12