stimulation of the central ends of nerves, such as the vagus, which contain afferent respiratory fibres. The hyperglycæmia thus induced can, however, be invariably prevented by ventilating the lungs with pure oxygen gas; whereas, such a procedure does not prevent the increase in reducing power of the blood as a result of stimulation of the splanchnic nerve. It must be pointed out, however, that although it does not prevent the hyperglycemia, yet in animals thus treated the hyperglycemia is commonly not so marked as otherwise.

When the hepatic branches of the coeliac plexus are cut and the splanchnic nerve then stimulated no hyperglycemia is found to result, although in such cases the effect on the respiratory movements occurs as readily as if these nerves had been intact. In considering this experiment as evidence against the afferent nature of the fibres, it must, of course, be borne in mind that all nerve connections to the liver have been severed and that, therefore, the glycogenolytic function of this organ has been removed. from under nervous control. It is commonly believed, however, that respiratory interference leads to hyperglycæmia more probably by disturbing dextrose consumption than by causing an increased output from the liver.* Since, however, this is not as yet an established fact, the above proof must be considered as provisional.

Stimulation of the peripheral ends of the cut hepatic nerves causes marked hyperglycemia in 50% of the cases. The negative results in half the cases are to be accounted for by the fact that, in my experiments, no attempt was made to dissect out the individual nerve fibers, but the electrodes were tied around the mass of nerve-containing connective tissue running to the hilus of the liver after it had been dissected free from the portal vein and cut between mass ligatures. In certain cases therefore most, if not all, of the electric current must have been short circuited through connective tissue. For purposes of the above argument, however, a positive result in half of the cases is sufficient to warrant the conclusion that the hepatic nerves contain efferent fibres which influence the sugar production in the liver and this fact lends support to the belief that the fibres in the great splanchnic nerve. are of similar nature.

II. STIMULATION OF VASOMOTOR FIBRES LEADING TO
DISTURBANCE IN THE HEPATIC CIRCULATION

However produced, asphyxia is associated with hyperglycemia. Thus, as explained above, interference with the respira

Underhill: Journal of Biological Chemistry, Vol. I, p. 126, 1905-06.

tory movements by stimulation of sensory nerve fibres causes it, as do also such drugs as nicotin, pipiridin, ether, morphin, etc., which act on the respiratory center. Disregarding, for the present, the exact mechanism leading to this result of asphyxia, we may nevertheless admit the possibility that a local asphyxia of the liver would likewise cause an abnormally rapid glycogenolysis with a consequent hyperglycæmia. Such a local asphyxia of the hepatic lobule would, of course, follow constriction of the supplying blood-vessels, and by means of such a mechanism as this, it might be, that splanchnic stimulation causes hyperglycemia.

That such, however, is not the case, I have shown by the study of the behavior of the reducing power of the blood after ligation of the hepatic artery, and after temporary clamping of the portal vein. By neither of these operations is hyperglycemia induced, unless when, in the latter case, the vein is clamped for longer periods of time than two minutes. Under these latter circumstances hyperglycemia follows, but the marked lowering of arterial blood-pressure which results from prolonged clamping is, as explained above, an interfering factor, so that the experiments in which the clamping is for so long a period of time are not of very much value in connection with the present discussion. The establishment of an Eck fistula (anastomosis of the portal vein to the inferior vena cava) is not followed by glycosuria* nor does thrombosis of the portal vein have such a result. It may seem to you inconsistent that prolonged clamping of the portal vein should cause hyperglycemia, whereas complete removal of the portal blood from the liver, as is brought about by Eck's operation, should not do so. A little consideration of the exact conditions in the two cases, however, offers a satisfactory explanation; for, in the one of these (i. e., temporary clamping of the vein) the sugar which has accumulated in the liver as a result of prolonged removal of the portal blood is immediately afterwards flushed into the systemic circulation: whereas, in the other (i. e., Eck fistula), such is not the case, the sugar being so gradually removed from the liver that it does not overwhelm the blood and therefore does not cause hyperglycemia.

By a process of exclusion, therefore, we are driven to conclude that the nature of the above fibres in the great splanchnic nerves must be secretory. They must be fibres which control

*Macleod: Art. "Eck's fistula"; Pathological Studies. tions, Aberdeen University, 1905.

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the production or the activity of glycogenase, the amylolytic ferment of the liver. It is, of course, a very difficult matter to furnish direct evidence of the truth of this conclusion. In the case of glands such as the salivary and gastric, whose activities are undoubtedly to a large extent under nervous control, observations on the rate of secretion is all that is necessary to furnish the desired evidence, but in the case of glycogenase production by the liver, we are compelled to judge of its rate of production by the effect which it has in influencing the output of dextrose by this organ.

Many secretory mechanisms under nervous control are paralyzed by the administration of atropin. I have found, however, that atropin does not interfere with the above described effect of stimulation of the splanchnic nerve. Such a result cannot, of course, be taken as negative evidence of the existence of glycogenase secretory fibers, for the mechanism here involved is more akin to that of a ductless gland, on the supposed secretions of which atropin has no effect.

It was further attempted to decide the question by making a comparison of the amount of glycogen in the liver of the turtle before and after stimulating the spinal cord. In the large snapping turtle the liver is of large size and consists of two lobes joined together by a narrow bridge of liver substance. One of these lobes was, first of all, removed, a shoe lace being tied around the stump as a mass ligature to prevent hemorrhage, and its glycogen content determined by the method of Pflüger.* The spinal cord was then stimulated with the faradic current for one hour, after which the glycogen was determined in the remaining portion of liver. No conclusive results could, however, be obtained.

Finally, experiments were conducted dealing with the glycogen content of portions of the liver of the dog removed after anastomosing the portal vein to the inferior vena cava. By diverting the portal blood in this way, very little hæmorrhage attends removal of a lobe of liver, provided that the stump be enclosed in a flat mass ligature (shoe lace). In one series of observations, the glycogen was determined by Pflüger's method, in a piece of liver (about 20 gr.) removed immediately after making the fistula and in another piece removed one hour later. In another series of observations, the great splanchnic was stimulated in the interval between removal of the two pieces of liver. It was found that when the anastomosis had been readily estab*Pflüger: Archiv, f. d. ges. Physiologie. Bd. CXIV, S. 231, 1906.

lished, and the blood-pressure had recovered well after the operation, that with no stimulation of the splanchnic nerve the percentage rate of glycogenolysis in one hour in two experiments was 24.3 and 22.6.* In two other experiments without stimulation, but in which there was low mean arterial blood-pressure after establishment of the anastomosis, the percentage rate of glycogenolysis was 40 and 74.1. In four experiments in which the splanchnic nerve was stimulated for one hour after making the anastomosis, the percentage rate of glycogenolysis was 70, 100, 89.2, 83.1 and 39.4 and in one experiment in which the first piece of liver was removed in one-half hour after making the anastomosis, and the second in one-half hour later-during which time the nerve was stimulated-the above value stood at 50.8.

It will be seen that a distinctly more rapid disappearance of glycogen occurred when the nerve was stimulated.

The only circulation through the liver in these experiments is that of the hepatic artery. When the mean arterial bloodpressure is greatly lowered by the operation, then the hepatic artery blood-supply is insufficient to prevent a glycogenolysis similar to that seen immediately after death (postmortem glycogenolysis). In such cases, therefore, a high percentage glycogenolysis is observed in one hour. With good blood-pressure on the other hand, the hepatic arterial blood-supply is sufficient to prevent the advent of postmortem glycogenolysis and a low percentage change is observed.

When with good blood-pressure the splanchnic nerve is stimulated there will result a constriction of the hepatic artery which, according to the above argument, must, by diminishing the arterial blood-supply to the liver, tend to accelerate glycogenolysis. In our results, however, the rate of this has been found, on an average, distinctly greater when the splanchnic nerves. were stimulated in animals with good blood-pressure than it is in those cases with low arterial blood-pressure but no stimulation of the splanchnic nerve; which fact, can, of course, mean only one thing, viz., the presence of true glycogenase secretory fibers in the greater splanchnic nerve.

These last mentioned experiments present, however, one serious fault, viz., that the rate of glycogenolysis in the liver in the stimulated cases is compared with this rate in the liver of

*This value is obtained by subtracting the percentage amount of glycogen found in the second piece of liver from that found in the first piece, and then calculating this value as percentage of the amount found in the first piece of liver.

another animal in which no stimulation is practised. It might be claimed that the differences observed are merely accidental, since the rate of glycogenolysis varies greatly in the livers of different animals. We are at present engaged in another type of experiment which will remove this objection, but the results are not yet ready for publication. After establishing the Eck fistula, a piece of liver is removed; the animal is left undisturbed for 30 minutes when another piece of liver is removed, the splanchnic nerve is then stimulated for another 30 minutes, at the end of which time a third piece of liver is removed. Glycogen estimations are made on the three pieces of liver and the rate of its disappearance compared for the first or resting half hour and for the second or stimulated half hour.

Restoration of Intestinal Continuity Following
Artificial Anus, with Illustrative Cases

By JOHN YOUNG BROWN, M. D.

Surgeon in Chief, St. John's Hospital, St. Louis, Mo.

In three comparatively recent cases, the writer has performed bilateral intestinal exclusion for the relief of artificial anus. The ease with which he was able to restore the intestinal continuity by this method, and the satisfactory results obtained, were so far superior to those he has gotten from the usual methods employed in the treatment of this condition that he has been prompted to report the cases in detail.

CASE I. Umbilical Hernia (strangulated). The cecum, appendix, ascending and transverse colon were found gangrenous in the hernial sac. Artificial anus was established followed later by bilateral intestinal exclusion and restoration of intestinal continuity.

The patient was 47 years old, colored, mother of 10 children, admitted to the hospital suffering from a huge, strangulated, umbilical hernia. Duration of strangulation, 18 hours. The condition of the patient on admission was bad. On examination, a large, oval, umbilical hernia, the size of an adult head, tightly constricted at the umbilical ring, was found. The skin over the hernia was blistered from the hot applications used prior to admission. She was immediately prepared for operation after washing out stomach.

Primary operation under ether anesthesia. Transverse, elliptical incisions were made, surrounding the hernia. These were deepened to the base of the hernial protrusion, it being the intention to do a radical Mayo operation if conditions permitted.

Read before the Academy of Medicine of Cleveland, May, 1908