A HORMONE MECHANISM FOR GALL-BLADDER CONTRACTION AND EVACUATION

Abstract

The numerous reports in the literature showing the marked efficacy of fats, egg-yolk and meat protein in emptying the gall bladder convinced us that the effect of %ecretin " on the evacuation and motor activity of the gall bladder should be studied, since it is well known that these substances stimulate the pancrew, and that " secretin " (very impure solutions) promotes the formation of bile. With this objective in mind, we have performed several series of experiments, the results of which prove, we believe, that a hormone mechanism is concerned in gall-bladder contraction and evacuation. For some time Ivy, Kloster and Lueth (1927) have been working on the purification of 3ecretin " for the purpose of perfecting a pancreatic function test for man. In our work we have used the preparations prepared for us by them. The solutions furnished us were " highly purified, " were vaso-dilatin-free, and have had no objective deleterious action when injected intravenously in succ&ion in anesthetized or unanesthetized animals. In a search of the literature it has been found that several investigators have attempted to determine whether or not a humoral mechanism is concerned in gall bladder evacuation. Boyden (1926a) found that the transfusion of blood of fed or starved cats caused a partiai evacuation of the gall bladder. He does not state that he tested the compatibility of the blood of the cats used. He interpreted the results of hi8 experiments on this phase of the gall bladder question as meaning that the *gall bladder is sensitive to bodily conditions which effect changes in the circula&ng blqod. Whitaker (1926) injected doses of " secretin " prepared by the Bayliss-Starlin& method with negative results. Copher and Illingworth (1926) 'mjected " secretin " with negative results; but they do not state' the method by which the " Becretin " used by them was prepared. Brugsch and Hors-ters (1926) placed a coridom balloon in the gall bladder of dogs and found that 10 cc. of a preparation of Dale and Laidlaw (1912-13) " secretin " caused a confraction and rhythmic changes of the gall bladder, and " hypo- A. C. IVY AND ERIC OLDBERG physin " relaxed it. They observed that histamine (10 mgm.) caused the gall bladder to contract. They concluded that histamine and " secretin " act alike, the latter being the physiological agent. They did not make a simultaneous blood pressure tracing to rule out vaso-dilatation as being a factor, which we know is a factor. EXP~IMENTS. On cats without cystic duct clamped. The cat was barbi-talized, the common bile duct was cannulated, and a cannula was placed in-to the gall bladder through a small opening in the fundus. The cannula in the gall bladder was connected to a glass tube, which served as a manom-eter. The glass tube was connected to a recording tambour. A simul-taneous carotid blood-pressure tracing was made. Four such experiments were performed. Within one minute after the intravenous injection of the " purified secretin " (2 mgm. of solid material), the intra-gall-bladder pressure was increased, and steadily increased until it amounted to from 2 to 3.5 cm. of bile pressure. About four minutes after the injection the bile flow was augmented. The pressure started to decline in from 3 to 1 hour in these experiments. The blood pressure, respiration and heart rate were unaffected by the injection. Normal saline controls proved negative. On cats with cystic duct clamped. To avoid entirely the possibility that the increase in gall bladder pressure might be due to an inflow of bile, which was not likely, we clamped the cystic duct. Three experiments of this kind were performed. In all experiments the gall-bladder pressure was raised on the injection of the " secretin, " but not to the extent that occurred in tke preceding experiments. This difference, we believe, was due to some interference with the blood supply of the gall bladder, which is very difIicult to avoid in the cat on ligating or clamping the cystic duct. Atropine and histamine in cats. It was found that the " secretin " prep-aration caused as much contraction after the injection of 1 mgm. of atropine as it did before the injection of atropine. Two such experiments were performed. The injection of 0.5 mgm. of histamine intravenously in the cat caused a decided fall in blood pressure without changing the intra-gall-bladder pressure. This effect is different from that which occurred in the dog, which will be shown later in this paper. On dogs with the cystic duct clamped. Dogs were anesthetized with barbital (0.200 gram per kilo body weight) or with " light " ether. The pancreatic duct was cannulated, the cystic duct was clamped above the opening of the right hepatic duct, and the fundus of the gall bladder was cannulated. The cannula was connected to a glass tube which served as a manometer, which in turn was connected to a recording tambour. The carotid was connected to a recording blood pressure manometer. In many experiments the cystic artery was included in the clamp, it being impossible to prevent this without anatomical dissection, which we wished to avoid.