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ing alternate perfusion with saline and 0.1 hydrochloric acid. Sodium bicarbonate was perfused or propanthelene given intravenously, or both, if pain was provoked. The patients tested were all unaware of the nature of the perfusing fluid. Eight of 15 normal volunteers experienced chest pain on acid perfusion. Four of lO patients with angina also experienced pain, two stating that it was identical with their usual anginal symptom. ECG changes were noted in one patient. Of 29 patients known to have esophagitis, 28 felt pain on acid perfusion, and all experienced virtually complete relief on neutralizing with sodium bicarboN

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nate. Three of this group also complained of pain on perfusing with saline, and two obtained subsequent relief from bicarbonate. Motility responses to perfusions were variable, no constant relation between pressure waves and pain emerging. Bicarbonate, while almost invariably relieving acid-induced pain, did not always diminish motility. Intravenous propanthelene relieved pain in only a minority of patients. It was concluded that the test was a valuable aid in the diagnosis of esophagitis. lain E. Gillespie University of Glasgow Glasgow, Scotland

GASTROENTEROLOGY AT THE SURGICAL FORUM IN 1965: A REVIEW At the Sixteenth Annual Meeting of the Surgical Forum, sponsored by the American College of Surgeons and held in Atlantic City in October 1965, 248 lO-min papers were presented. Seventy of these papers described research work related to gastroenterology. The following survey cannot describe all of the papers related to the gut but will indicate the type of work currently being done by surgical investigators. Pancreas

Drieling and co-workers described the effect of total pituitary ablation on both the ecbolic and electrolyte secretory capacity of the canine pancreas. Complete hypophysectomy resulted in marked suppressions of maximal volume output, maximal bicarbonate secretory capacity, and maximal amylase production. The hypophysectomy-induced secretory depression was completely reversed by administration of ACTH, cortisone, 01' dexamethasone. Since in a previous study these workers had shown that adrenocorticotropin was ineffective in reversing the suppression of fluid, electrolyte, and enzyme after adrenalectomy, they concluded that these functions are adrenal-steroid dependent. Several papers were concerned with mechAbstracts of all papers mentioned in this review appear in Surg. Forum, volume 16, 1965.

anisms involved in acute pancreatitis. Kelly divided the pancreas of the dog into a dorsal and a ventral lobe while leaving intact the neurovascular pathways between both lobes and the animal. The ventral lobe was implanted in subcutaneous tissue of the anterior abdominal wall as a simulated heterotopic pancreas. After creation of a biliary pancreatic common channel, acute pancreatitis was produced synchronously in the in situ dorsal pancreatic lobe and in the simulated heterotopic ventral lobe. The author postulated a neurovascular mechanism as a possible explanation for these observations. Brown and associates reported that the susceptibility of the dog to pancreatitis induced by the low pressure infusion of a mixture of trypsin and sodium taurocholate into the major pancreatic duct is directly related to the zymogen granule content and storage enzymes in the pancreas at the time of the pancreatic insult. Mulder and co-workers found that acute hypotension due to hemorrhage is associated with cessation of mucin production in pancreatic ducts. They suggested that this depletion of mucin may render pancreatic tissue more susceptible to activated intraductal trypsin. In all cases of spontaneous pancreatitis secondary to irreversible shock, these workers found significant amounts of free trypsin in the pancreas. Using cross-circulation between an animal with acute pancreatitis

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and a normal partner, Apostolou and associates found that the lethal factor in acute pancreatitis is not often transferred in a fatal amount to a normal partner. Instead, the normal animal actively supported the dog with pancreatitis. When pancreatitis was induced 6 weeks later in survivors of previous pancreatitis or in the normal animals surviving cross-circulation experiments, all animals survived in contrast to the mortality rate of 90% in controls. These results were interpreted as indicating the presence of a humoral antigenic substance that is capable of producing a protective mechanism. Gilsdorf and associates measured pancreatic blood flow and secretion during stimulation of the hypothalamic regions in dogs. Posterior hypothalamic stimulation produced an increase in volume of juice that was low in protein and enzyme but high in bicarbonate and sodium, whereas anterior hypothalamic stimulation mimicked a vagal effect, with an increase in enzyme production without volume change. Gall Bladder and Bile Ducts

DePalma and co-workers observed in patients the effects of conventional T -tube drainage of common bile duct on the serum cholesterol. They noted a rapid and marked reduction of serum cholesterol within 4 days. The decrease in serum cholesterol was not necessarily related to relief of common duct obstruction since it occurred after drainage of nonobstructed bile ducts in three cases. Hilburn and Barnett compared the rates of gallstone dissolution in gall bladder of three groups of dogs: one group with total vagotomy, another with selective vagotomy with preservation of hepatic branch of anterior vagus, and the third with no vagotomy. Gallstones of human beings disappeared rapidly from the gall bladder of dogs with intact vagi or intact hepatic branch of the anterior vagus, but the rate of dissolution 9f the stone was significantly retarded in totally vagotomized animals. The authors suggested that this difference in time required for dissolution of the stones was related to stasis from gall bladder atony resulting from denervation.

Lucus and associates used 20% microbarium suspension in normal saline for cholangiographic studies in dogs and human beings. They found no evidence of inspissation, aggregation, or retention of the barium suspension, and believed that the technique gave better delineation of both the smaller biliary radicals and the periampullary region than when meglumine diatrizoate (Renograffin) was used. Thomford and Hallenbeck described a technique of choledochojejunostomy in which part of the Roux-en-Y limb proximal to the anastomosis was brought through the abdominal wall as an external fistula. This operation in dogs permitted direct access to the biliary intestinal anastomosis after operation and allowed inspection, calibration, and dilation of the anastomosis without surgical intervention. Gastric Secretion

Two papers were concerned with gastric mucus secretion. Thompson and J\1enguy reported that vagal stimulation had no effect on basal rate of secretion of mucus in antral pouches of dogs. Because these workers found that acid secretion is itself a potent stimulus of mucus secretion, antral pouches were used for evaluation of the vagal effect on mucus secretion. Insulin was not used for stimulating the vagus nerve because hypoglycemia per se inhibits secretion of mucus. Pearl and co-workers studied the effect of hypothalamic stimulation on mucus production in vagally innervated and denervated gastric pouches in cats. Low intensity stimulation produced an increase in gastric mucin production in vagally innervated pouches and a decrease in mucin production in vagally denervated pouches. Hardacre and associates measured the gastric acid output of Heidenhain pouches in dogs with defunctionalized segment of duodenum and jejunum, which was anastomosed to the terminal portion of the ileum. In some dogs with a defunctionalized segment, the bile and pancreatic ducts were transplanted into functioning small bowel approximately 10 em from the gastric outlet. Hypersecretion of acid was marked in both groups of animals, and the authors

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interpreted these results to indicate that an Further studies will be necessary to clarify inactive duodenum not properly inhibited the nature of this gastric inhibitor substance by normal digestion of food stimulates gas- in the lymph of the thoracic duct. Mignon and associates studied the in vitro tric secretion by a blood-borne agent. Using dogs with a Heidenhain pouch, vag- binding characteristics and the in vivo effect ally innervated antral pouch, and gastroje- on iron absorption of gastric juice from norjunostomy, Passaro and Goodman measured mal dogs and dogs with iron deficiency and the output of acid from the Heidenhain found no evidence for the existence in gaspouch in response to histamine and exog- tric juice of either group of animals of a enously administered gastrin. Similar de- chelating factor which facilitated iron abterminations were made while the vagally sorption. Their results suggest that any innervated antral pouch was irrigated with effect of gastric juice observed on iron ab0.25% acetylcholine solution, and the re- sorption may be due to the acid component sults indicated a potentiation between en- of gastric secretion. dogenously administered gastrin and histaSachatello and Gobbel measured the outmine, additive effects of endogenous gastrin put of hydrochloric acid of innervated gasand exogenous gastrin, and no evidence of tric pouches before and after the chronic adinhibition by either endogenous gastrin or ministration of compound 48/80, a basic amine which releases histamine from mast an antral chalone. Weinshelbaum and Ferguson used autog- cells. During the period when these dogs raphy to observe distribution of radioactiv- were unresponsive to continued administraity in the gastric wall of mice, during secre- tion of compound 48/80, intravenously adtion stimulated by histamine labeled with ministered gastrin, alcohol, and insulin proradioactive carbon in the imidazole ring. duced a marked secretory response similar They found that argentaffin cells possessed to that observed in the control period prior an ability to bind histamine or its metabo- to the administration of compound 48/80. lites and therefore suggested that these cells Significant degranulation of mast cells was function as a gastric repository for hista- observed in animals given compound 48/80. mme. These results indicate that the stimulus for Several papers were concerned with inhi- gastric acid secretion may be through a bition of acid secretion. Schulte and Ellison mechanism other than the release of stored reported that they were unable to inhibit histamine. maximal histamine-stimulated hydrochloric Liver and Portal Circulation acid secretion in dogs with heparin in a dose of 2 mg per kg of body weight. Woods reDeBenedetti and co-workers reported ported that secretin reduced the gastric acid that external drainage of the thoracic duct output in response to betazole in human be- in normal animals had no significant effect ings. However, the appearance of bile in on portal or vena cava pressures, or on hethe gastric aspirate raised the possibility patic blood flow. In animals with congestive that hydrochloric acid was neutralized and cirrhosis and ascites, lymph flow and prestherefore not inhibited. The fact that re- sure in the thoracic duct were markedly induction of concentration of hydrochloric creased. External drainage of the thoracic acid was greater than decrease in volume of duct in these animals relieved ascites only secretion further indicated this possibility. when fluid replacement was delayed or deRudick and co-workers reported that a sub- ficient. Their results indicate that therastance in the lymph of the thoracic duct peutic effects of a thoracic duct fistula on of dogs inhibited output of hydrochloric ascites are due to removal of large quantiacid in response to histamine and gastrin. ties of protein-rich fluid from the body, and Because this substance was present in the in many respects, the mechanism of action lymph of fasting dogs and absent in lymph is similar to that of abdominal paracentesis. collected after a liver or fatty meal, these Heel' and co-workers measured urinary workers suggested that the substance might volume, sodium, potassium, and osmolality be released during the interdigestive phase. before and for 5 hr after 500 ml of a 0.9%

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sodium chloride solution was administered intravenously to anesthetized fasting dogs. When the studies were repeated 3 and 7 weeks after portacaval shunt was performed, a sustained depression of sodium excretion was not observed. Their results did not support the contention that sustained abnormal retention of sodium occurs after portacaval shunt in normal dogs. These workers did not observe any significant alterations in total sodium and potassium secretion, urinary osmolality, blood volume, glomerular filtration rate, or renal plasma or renal blood flow. Marchioro and associates performed partial portacaval transposition in dogs by attaching the distal end of the transected vena cava to either the right or left mean portal branch, leaving the other half supplied with splanchnic venous blood. They found that the part of the liver supplied with caval blood was shrunken in seven dogs examined after 70 to 94 days. The glycogen content of the hepatic fraction receiving vena caval flow was always reduced, with only 42 to 83% of the concentration present in the lobes receiving splanchnic flow. These workers interpreted the results to indicate that the competing liver fraction, which received normal portal blood flow, operated at a physiological advantage, presumably due to specific substance presented to it in high concentration by blood returning from intestinal tract. The observed differences in the liver fractions were not explicable by greater oxygen availability in the splanchnic venous blood, since the oxygen content of vena caval blood was at least as high as that in the superior mesenteric vein. Norman and co-workers reported that in the monitored ex vivo isolated perfused porcine liver system with adjusted inflow pressures, flow rates, pH, p02, pC0 2 , and oxygen saturations of hemodiluted perfusates, the rate of ascites formation is proportional to degrees of outflow-tract occlusion. Increases in outflow-tract pressures resulted in increased rates of ascites formation with essentially unchanged specific gravities, cellular contents, and protein concentrations. Kline and associates made quantitative studies of the cerebral astrocyte population

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in control dogs and animals with complete and incomplete portacaval shunts. Significant elevation in astrocyte counts were seen only in the completely shunted animals, and the astrocyte counts correlated with severity of neurological findings. Additional work on the cause of hepatic coma was reported by Yang and co-workers. They studied the capability of the brain in comatose and anhepatic dogs to metabolize glucose and found that the brain tissue in these animals had a decreased ability to metabolize glucose. The specific localization of this metabolic defect was not evident from their studies. Bibler, Condon, and Nyhus produced hepatic insufficiency in dogs by end-to-side portacaval shunt and simultaneous resection of 70% of the liver. When hepatic failure was advanced, each animal was connected to a bovine liver and allowed to perfuse this heterologous organ for 2 hr. :1\1etabolism of sulfobromophthalein and galactose improved during perfusion. Alkaline phosphatase, uric acid, venous and arterial ammonia, and plasma proteins (other than fibrinogen) showed no consistent changes. Immediately after perfusion, protein of bovine origin was present in the plasma of each dog as demonstrated by immunoelectrophoresis. When subsequently challenged by bovine plasma given intravenously, two of the dogs in hepatic failure exhibited immediate anaphylactic reactions. These results indicate that heterologous liver perfusion in dogs can lead to active sensitization and that anaphylaxis may result from a subsequent exposure to bovine protein. Two studies were concerned with optimal flow rates during ex vivo liver perfusion. Cuello-Mainardi and associates reported that the minimal blood flow at which the ex vivo pig liver can function effectively is between 0.75 and 1.0 ml per g of liver per min. Tait and co-workers also defined optimal conditions for hepatic function in nonpulsatile perfusion of the isolated pig li\"('r. Faris and associates studied the hepatic function of liver homografts of long term (98 to 442 days after operation) dog survivors. Of nine animals studied, one had normal hepatic function as measured bv serum bilirubin, serum glutamic-oxaloaceti"c

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transaminase, alkaline phosphatase, sulfobromophthalein retention, prothrombin time, and serum proteins. The other eight animals showed varying degrees of hepatic dysfunction. Windsor, Thompson, and Orloff measured gastric secretion and blood histamine before and after performance of portacaval anastomosis in dogs with congestive cirrhosis, portal hypertension, and massive ascites produced by ligation of hepatic veins. A significant depression of gastric secretory response to histamine and test meal developed in every dog with ligated hepatic veins. Immediately after the portacaval shunt was constructed, severe gastric hypersecretion developed in all dogs. Studies of arterial blood histamine after a meat meal showed no significant differences between the two groups of dogs. The results indicate that histamine is not the agent responsible for gastric hypersecretion after portacaval shunt. Shock Several papers were concerned with endotoxic shock. In an attempt to determine the localization of endotoxin in dogs, McManus and associates used a specific fluorescent staining technique for endotoxin and found fluorescence in the tissues, particularly in the walls of blood vessels, of the animals that received endotoxin. Because there was no difference in the localization of endotoxin in animals treated with hydrocortisone, these workers suggested that the beneficial effects of cortisone in dogs given endotoxin do not result from alteration in localization of the endotoxin. Brockman and Vasko studied the hemodynamic response to endotoxin, Escherichia coli (Difco) 5 mg per 1 kg of body weight, in different species: dog, cat, and rhesus monkey. They found that in the dog, cardiac output and aortic pressure decreased as a result of diminished venous return. The aortic pressure decrease was largely due to pooling of blood in the liver. The cat and monkey also had significant hepatic pooling but of a lesser degree than that observed in the dog. The major species difference was a marked increase in pulmonary resistance in cat and monkey. Bounous and co-workers suggested that the

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effect of sudden cessation of mucus production on the intestinal barrier to intraluminal toxins might have a role in the pathogenesifl of irreversible shock as seen in the intact dog subjected to hemorrhage. Bains and associates observed mesenteric microcirculation in dogs shocked by intravenous endotoxin (E. coli endotoxin, 3.5 mg per 1 kg of body weight, intravenously) and noted that dogs treated with methylprednisolone intravenously had a more rapid return to preshock flow rates, less sludging of cellular elements, and less vascular sphincter spasm than did control animals. Miscellaneous Das and Rusk found viable bacteria almost uniformly in both arterial and venous blood of normal dogs. They believe that recognition of this observation is important, because bacteria may seriously interfere with experiments which are not designed to allow for this. Williams studied the hemodynamic alterations in dogs subjected to acute gastric dilation. Since the abdomen was left open during the experiments, impaired venous return was not thought to be the pathogenesis of hypotension. Absence of significant alterations in blood volumes indicated that fluid loss into the stomach was of little importance in the production of the hypotension. It was the author's opinion that hemodynamic alterations of decreased flow in the descending portion of the aorta, the superior mesenteric artery, and the abdominal portion of the aorta were on a reflex basis with the afferent pathway of the reflex carried in splanchnic nerves. This conclusion was based on the fact that division of the splanchnic nerve prevented any hemodynamic alterations. Engler and coworkers also studied hemodynamic changes in experimental acute gastric dilation and concluded that the arterial hypotension is a result of decreased venous return secondary to mechanical obstruction of the intraabdominal inferior vena cava. Meredith measured the motility of the small bowel in dogs before and after total adrenalectomy and also after adrenal replacement therapy. When motility was correlated with serum sodium and serum potas-

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sium concentrations it was noted that the number of spikes, amplitude, and frequency did not change with sodium depletion or with changes in potassium levels. Lazarus and Warren described a technique for assessing vascular integrity of small bowel in dogs. A 10% solution of alphazurine 2G dye administered intravenously in a peripheral vein was reported to clearly demarcate segments of small bowel with irreversible ischemia. Before applying this method to human beings, one should remember that this dye can produce a fatal anaphylactoid reaction. Lyons and co-workers reported that segments of canine small bowel which was preserved by hyperbaric oxygen and hypothermia retained metabolic activity as well as normal architecture. Metabolic activity was determined by means of studies of absorption and peristalsis. Austen and McLaughlin studied the effects of pulsatile and nonpulsatile blood flow on isolated segments of dog small bowel maintained in vitro. They reported that nonpulsatile blood flow resulted in impairment of metabolic function and gross changes in the structure of the bowel within 6 hr. Pulsatile blood flow did not seem to

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result in marked impairment of metabolic function or gross changes in the bowel or mesentery after periods of perfusion up to 18 hr. Glotzer and Pihl used tubular pedicle grafts of upper colonic mucosa to line the rectum previously stripped of mucosa from the inferior mesenteric artery to the dentate line. Fecal continence, which was determined by response of the anal sphincter to balloon distention of the reconstructed rectum and observation for fecal soiling, was reported to be preserved by dogs undergoing the procedure. Stahlgren and associates reported that enteric-coated potassium chloride, in combination with thiazides or alone, produced focal mucosal ulceration in intestine of dogs with partial obstruction. The authors concluded that mucosal changes resulted from local toxic effect of the drug and suggested that the mucosal changes may represent an initial stage of the clinical syndrome consisting of intestinal stenosis and mucosal ulceration. Donald C. McIlrath, M.D. Mayo Clinic and Mayo Foundation Rochester, Minnesota