6I2.4I3:6I6.5-00I. I. operation for exteriorization of a portion of the small intestine caused a. supra-renal bodies.

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1 6I2.4I3:6I6.5-I. I THE EFFECT OF SOME ACCIDENTAL LESIONS ON THE SIZE OF THE SPLEEN. By JOSEPH BARCROFT. (From the Physiological Laboratory, Cambridge.) OBSERVATIONS made by Barcroft and Florey [1929] showed that the operation for exteriorization of a portion of the small intestine caused a shrinkage of the spleen which persisted for days and perhaps weeks after the actual operation. Moreover, the shrinkage was accentuated by perforation of the gut leading to peritonitis. Further observations were made in which the abdomen was opened [Barcroft, 1931], a loop of intestine was exposed for a few minutes under aseptic precautions and replaced in the abdominal cavity, which was then closed. The result was a contraction of the spleen lasting for some days. These operations may be contrasted with such a lesion as a hernia, which is followed by no contraction of the spleen. Fig. 1 shows the alteration which took place in the volume of the organ, (1) when the operation of excision of the superior cervical ganglion was performed, (2) when a hernia developed just ventral to the spleen, so that the abdomen was closed only by the integument, and (3) when the operation was performed successfully to cure the hernia. In the cases (1 and 3) of operation there was a marked contraction of the spleen which lasted some days. In the case of the hernia, however, caused presumably by a stitch giving way in the region of the spleen, there was no contraction. We do not know the precise stimulus which was responsible for the contraction. In the present case it was presumably a chemical one, for the spleen had been denervated. But granting the chemical nature of the stimulus, there remains unsettled the question of whether the stimulant was a product of tissue breakdown, of bacterial action, or was adrenaline which might have been liberated as the result of some action of nervous origin on the supra-renal bodies. Four experiments were performed [Barcroft, 1931] in which the superior cervical ganglion was excised. In two cases the spleen had been

2 LESIONS AND SPLEEN. denervated during exteriorization, and in two others it had not. In all cases the spleen contracted as the result of the operation on the neck. The contraction was more marked in the innervated spleen, but not significantly so. It was hoped that by observation of the pupil on the side from which the ganglion had been removed, some information would be obtained as to the presence in undue amount or absence of adrenaline Cs S z i Li - w LL c) C14 co A Q. 2 :. Y_ O- r Q v- r- ILuwU' I 1-. T95 A _- C14 co v- Co Co r- I I Swelling Jke... dlue. ~~~..5 to Hernia g 9 8 v _ 7 i 6 'Q 5 5.o 2 4 A Fig. 1. Volume of spleen following (1) excision of superior cervical ganglion, (2) develop. ment of a hernia, (3) operation for hernia. Spleen reduced to seven-twelfths of its linear dimensions. in the blood. This hope was not fulfilled, the dog being an unfavourable animal for observations on the sensitization of the pupil to adrenaline. Another dog (Nina), the spleen of which was denervated during exteriorization, also yielded an interesting result. The superior cervical ganglion was removed and the spleen contracted and was regaining its normal size when, nineteen days after the operation, it again suddenly shrank; the bandage had caused a considerable abrasion under the neck

3 438 J. BARCROFT. It took nine days for the wound to heal, during which time the spleen remained shrunken and relatively colourless. Apart from the fact that the spleen had been denervated, the interesting points about the lesion were that it was purely superficial and not severe (Fig. 2). During the winter of a phenomenon appeared in a number of animals which suffered from necrosis of considerable areas of skin. The necrosis developed only in those animals on which operations had recently CS- 3 - o O.~~~~s Days -- before, -# after, operation Fig. 2. Changes in volume of spleen following (1) excision of superior cervical ganglion, (2) abrasion of skin under neck. been performed. Usually about a week, but in one case three weeks, elapsed before it became evident that a large patch of skin was dead and had to be removed. When that was done and the bare area dressed systematically the animals made a healthy recovery. The injury was quite superficial and the animals did not appear to be in pain, their spirits and appetites being excellent. Without going into the various possibilities which might account for this phenomenon, the fact that it was confined to a certain category of animals ruled out a general epidemic. Experiments were instituted to test whether the operation had so lowered the resistance of the animals

4 LESIONS AND SPLEEN. 439 that they fell a prey to infection which other dogs defied. The first of these experiments showed the true nature of the trouble. In order to obtain controls two animals were given an anesthetic each for an hour and subjected to all the routine procedure of an operation, but no operation was actually performed upon them. These two, so far from experiencing no trouble, were much more seriously affected than the rest. The areas of necrosed skin were larger, the damage went deeper and appeared earlier. The operating table was of the type in which a copper top is warmed by an electric bulb beneath. Although the animal lay on perforated zinc normally separated by an air space from the copper and with a sterilized cloth between its body and the zinc, the events showed that the surface of the skin had been exposed to too high a temperature. Clearly this accident could not have occurred with the type of table kept warm by means of a hot-water tank, as the effect depends upon the production of heat at a rate faster than it is conducted away. The most severe case, that of Nina, may be taken first. Protocol. Jan. 2, Nina (spleen exteriorized and denervated Nov. 2, 1929) was placed on the dissecting table under C.E. mixture, as when animals are normally operated on for exteriorization of the spleen. The perforated tray and cloths were between her hair and the table. No operation was performed. She lay so for an hour. The spleen shrank in the usual way under anaesthetic. Jan. 22. Nina was somewhat stiff in her gait and dull in general appearance. The hair on the right side was darkish looking as though a burn might develop, but as yet there was nothing further to be seen. Jan. 23. Temp F. Skin nowhere broken, but two areas obviously necrosed. They were congested and the hair was loose. One area was in the flank, the other between the ribs and the thigh. Jan. 24. Temp F. Affected areas as in Fig. 3. Jan. 25. The care of the areas was handed over to Major Linton, R.A.M.C., who did the subsequent dressings, removing the necrosed skin and tending the affected areas with Eusol. Jan. 26, 27 and 28. The bare areas extended and it became evident on the 28th that the damage had penetrated to the muscle. Temperature rose from 12 to 13-6 F. Jan. 29. Temp F. No appearance of pain. Vomited whilst being dressed; no appetite. Jan Dog died. It is worth putting on record, though of no great interest in the present connection, that the mental condition of the animal, though lacking its usual brightness, was quite tolerable, and apparently equal to that of many rather phlegmatic dogs. On both January 28 and 29 she took interest in what was going on about her, her rectal temperature on the 28th being 13.6 and on the 29th 88-5' F. On the latter day her

5 44 J. BARCROFT. Fig. 3. Affected areas of skin in Nina. Black =skin dark. Cross-ruled= hair falling out (each square=1 sq. cm.). Outer part =skin probably affected S 4 3 '~2 Days <- before, -- after, control experiment Fig. 4. Changes in volume of spleen of Nina after control experiment.

6 LESIONS AND SPLEEN. condition appeared bright enough to make me doubt the thermometer reading, and indeed not until the temperature had been taken three times and by two different thermometers did I accept it. Thus over a range of 15 F., or more than 8 C., the animal was quite compos mentis. The changes in volume of the spleen are shown in Fig. 4. A similar experiment was performed on Bell on Jan. 21st, i.e. before the result of that on Nina had revealed itself. Bell differed from Nina Before anslshetic (C.E) co.6 5 IUnder aneasthetio Fig Days -* after control experiment Changes in volume of spleen of Bell after control experiment. in three respects: (1) the spleen was not denervated, (2) the animal recovered, (3) the spleen only remained in a state of extreme contraction for a few days. The lesions were of the same general nature as those of Nina, i.e. one in the flank and another behind the ribs. The first portions of dead skin were removed on January 26th and the wound kept clean with Eusol. The animal "ran" rather a high temperature. Jan. 27 Jan. 28 Jan. 29 Jan F F. 15 F. 13 F.

7 442 J. BARCROFT. Protocol. Procedure as with Nina and earlier observations similar. Jan. 31, Both areas were reported clean and the surfaces healthy and granulating. Feb. 15. Area (1) flank dressed with amyl salicylate, area (2) with vaseline. This was continued up to Feb. 22, when the amyl salicylate dressing was stopped and both wounds were dressed with vaseline. In judging of the amyl salicylate dressing it should be said that while no benefit was derived from it, two facts must be borne in mind, firstly it was not used from the start and secondly it seemed less soothing-the dog was inclined to rub the area dressed with salicylate and not that dressed with vaseline. Feb. 29. Area (1) healed, (2) healing rapidly. Mar. 3. Both areas healed. The measurements of the spleen, Fig. 5, show that the maximum of shrinkage was on the second day after the injury, that is to say, before the skin had broken, and that at the end of a week the spleen had returned almost to its ordinary size, even though there were two large granulating surfaces. In the light of these two experiments it is now possible to interpret some others in which the necrosed areas were much less extensive, and what is perhaps of interest, the necrosis was not evident for a much longer time after the exposure of the animal to warmth. Protocol. TiHey II, spleen denervated and exteriorized on Dec. 17, The shrinkage of the spleen ran its usual course till the ninth day; the organ shrank rapidly till the fifteenth day, remaining contracted. On the twenty-first day the necrosis made itself evident and the dead skin was rewoved, the necrosed area cleaned thoroughly and dressed. By the twenty-fifth or twenty-sixth day the spleen was probably as large as it would have been had no skin lesion taken place. CONCLUSIONS. 1. Necroses of the skin, caused either by friction or unduly high temperature, are accompanied by a contraction of the spleen. 2. The contraction may come on before the skin is broken and therefore before bacterial action from without has occurred. 3. The contraction may pass off before the necrosed area has "dried up " if it is suitably dressed. 4. The above effects may be observed in denervated as well as innervated spleens. The thanks of the author are due to the Royal Society for a grant from which the expenses of the above research have been paid. REFERENCES. Barcroft, J. and Florey, H. (1929). J. Phy8iol. 68, 181. Barcroft, J. (1931). Vet. Journ. 87, 466.