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The site and characteristics of gastrointestinal electrolyte loss were investigated in eight dogs with experimental cholera induced by orogastric administration of 6-hr broth cultures of Vibrio cholerae, strain Ogawa 395. In these animals, all electrolyte losses originated in the small bowel, predominantly from the jejunum and ileum. The bicarbonate concentration of the small bowel fluid showed a progressive increase from duodenum, where it was less than that of plasma, to the terminal ileum, where it was significantly greater than that of simultaneously obtained plasma. Studies of the responses of chronic Thiry-Vella jejunal loops (five dogs) and chronic Thiry-Vella ileal loops (five dogs) to intraluminal challenge by cholera exotoxin demonstrated that all loops exhibited isotonic electrolyte loss for a 14-18 hr period after challenge. The bicarbonate concentration of fluid produced by exotoxin-challenged jejunal loops was not significantly different from that of plasma, whereas the ileal loops produced fluid with a bicarbonate concentration approximately three times that of plasma. The effect of intraluminal glucose on the response of canine gut to cholera exotoxin was investigated by perfusion studies in 12 dogs with chronic Thiry-Vella fistulae. Intraluminal glucose significantly enhanced isotonic fluid absorption in both jejunal and ileal loops. The net effects of glucose on isotonic fluid absorption were equal before and after intraluminal administration of crude cholera exotoxin. These data suggest that cholera exotoxin causes gut electrolyte loss by a mechanism independent of that by which glucose enhances sodium absorption.

In response to intraluminal challenge with crude cholera exotoxin, canine Thiry-Vella duodenal loops consistently produced isotonic fluid for a 24-36 hr period. Isotonic fluid production generally began within 15 min after challenge. Mean bicarbonate concentration of fluid produced by duodenal loops was 24±6 (SD) mEq/liter. Perfusion of exotoxin-treated duodenal loops with an isotonic electrolyte solution containing glucose 60 mOsm/liter caused a significant decrease in exotoxin-induced isotonic fluid output. The net effects of glucose on isotonic fluid absorption by perfused duodenal loops were not significantly different before and after administration of crude cholera exotoxin. The response of canine duodenal loops to challenge by cholera exotoxin differs from responses of jejunal and ileal loops in a) absence of a detectable “lag period” between administration of exotoxin and initiation of net fluid output; b) a longer period of fluid production following exotoxin administration; and c) a significantly greater net fluid output per unit length of gut. The mean bicarbonate concentration of the fluid produced by duodenum is less than that produced by ileum, but is not significantly different from that produced by jejunum. The duodenal response is similar to that of the more distal small bowel segments in that an effect on isotonic fluid movement is observed shortly after exotoxin administration and the maximum rate of exotoxin-induced isotonic fluid production is not reached until 4-5 hr after exotoxin administration. The basis for the consistent delay of 4-5 hr between intraluminal exotoxin administration and maximum gut fluid production has not yet been determined. Current data are consistent with the hypothesis that the rate of secretion of isotonic fluid induced by cholera exotoxin is not significantly different per unit length, in duodenum and ileum and that the lesser net fluid output in the ileum is due to the greater capacity for isotonic fluid absorption by the more distal small bowel segment.

Evidence is presented for an extra-adrenal factor which is necessary for aldosterone or DCA to produce chronic renal Na retention. To study this factor, the left kidney was transplanted to the neck, both adrenal glands and the right kidney were removed and the thoracic inferior vena cava was constricted in six dogs. For a period of two to three weeks, injection of 25 mg/day of DCA resulted in marked Na retention by the transplanted kidney and ascites formed. Neither renal venous hypertension nor the renal nerves were essential for renal Na retention under these circumstances since the transplanted kidney was denervated and its venous drainage was into the external jugular vein with a normal venous pressure. Removal of the caval ligature in four of the dogs was followed by a diuresis and loss of ascites in spite of continued injection of 25 mg/day of DCA. Similar changes occurred during the injection of aldosterone instead of DCA. Measurements of renal hemodynamic function, first, during Na retention and ascites formation and, later, after removal of the caval ligature showed levels of GFR and RPF during Na retention as high as or higher than those observed during the diuresis and subsequent Na balance. In three hypophysectomized dogs with a very low GFR and RPF, Na retention failed to occur during injection of 25 mg/day of DCA. Also, in three adrenalectomized dogs, administration of a large dose of DCA failed to produce chronic Na retention. Finally, four dogs with a large aortic-caval fistula were given 25 mg/day of DCA; sustained Na retention occurred in all four animals and ascites developed in two of the four dogs. A low rate of Na excretion in these animals was present despite a large postprandial rise in GFR. Available evidence indicates that the extra-adrenal factor is either 1) a humoral agent, or 2) some as yet undefined renal functional change.

A series of recent studies has demonstrated that the loss of gut electrolytes in cholera is caused by an exotoxin produced by Vibrio cholerae which have colonized the lumen of the gastrointestinal tract [1, 2].1 Canine Thiry-Vella jejunal loops consistently respond to intraluminal challenge with crude cholera exotoxin by production of isotonic fluid for an 18-24-hr period [3, 4]. The canine Thiry-Vella jejunal loop may thus serve as an assay for preparations of cholera exotoxin and provide a system in which the effect of pharmacologic agents on the response to exotoxin may be investigated. The current series of studies was designed (a) to delineate more precisely the response of ThiryVella jejunal loops to intraluminal challenge with cholera exotoxin, and (b) to study the effect of both intraluminal and intravenous ethacrynic acid on the response of the gut to cholera exotoxin.

Excerpt An effective fluid repletion regimen for treatment of Asiatic cholera has previously been delineated. During the 1963 and 1964 epidemics in Calcutta, a series of carefully controlled studie...