Recent studies indicate that long-term total parenteral nutrition (TPN) induces gallstone formation and acalculous cholecystitis in humans. Cholecystectomy is hazardous for these patients because they frequently have multiple medical problems and have undergone numerous abdominal operations. The present study was designed to develop a method to prevent TPN-induced gallbladder disease. The authors tested the hypothesis that a single daily intravenous infusion of cholecystokinin-octapeptide (CCK-OP) will prevent TPN-induced gallbladder stasis. Eleven prairie dogs received TPN for 10 days. Six of these animals were given a daily infusion of CCK-OP. Control animals were fed ad lib. Each animal's bile salt pool was labeled with intravenous 3H-cholic acid 16 hours prior to acute terminal experiments. The ratio ofgallbladder to hepatic bile 3H-cholic acid specific activity (Rsa) provides an index of gallbladder stasis. A Rsa of less than 1.0 indicates gallbladder stasis. TPN animals had a Rsa of 0.54 ± 0.13 (p < 0.01 vs. controls), indicating stasis of bile in the gallbladder. Daily CCK-OP infusions resulted in a Rsa of 0.92 ± 0.10 (p < 0.05 vs. TPN without CCK-OP), indicating that TPN-induced gallbladder stasis is prevented by daily CCK-OP. Control animals had a Rsa of 1.03 ± 0.06. The c4plesterol saturation indices of gallbladder and hepatic bile were not increased by TPN or CCK-OP. These data indicate that 1) TPN induces gallbladder stasis but does not increase bile lithogenic index; and 2) daily injections of CCK-OP prevent TPN-induced gallbladder stasis. SEVERAL RECENT REPORTS1-4 have documented an increased incidence of gallbladder disease in patients receiving long-term total parenteral nutrition (TPN). Although the pathogenesis ofthis phenomenon is not entirely clear, both human4'5 and animal studies6'7 suggest that the majority of gallstones that form during parenteral nutrition are pigment stones. In previous studies6'7 in the prairie dog, we have shown that TPN produces gallbladder stasis but does not alter either cholesterol saturation index or bile salt pool size. The observations of gallbladder distention8 and false-positive PI
Patients on long-term total parenteral nutrition (TPN) have an increased incidence of gallstones. To determine the pathophysiologic mechanisms responsible for gallstone formation in these patients, we fed three groups of prairie dogs intravenously for 10 days with continuous infusions of isocaloric, isovolemic, and isonitrogenous solutions with either 0, 25, or 50% of nonprotein calories provided as Intralipid. A fourth group of prairie dogs was hyperalimented with the 25% solution for 28 days. Control animals were fed Purina rat Chow ad libitum. Each animal's bile salt pool was labeled with iv 3H-cholic acid 16 hr prior to collecting gallbladder and hepatic bile specimens. The ratio of gallbladder to hepatic bile 3H-cholic acid specific activity (dpm/mol of bile acid), an index of gallbladder stasis, was significantly (p less than 0.05) lower in TPN animals (less than 0.65 +/- 0.19) compared to controls (1.07 +/- 0.11). This finding indicates that gallbladder stasis developed in all animals fed by TPN. TPN did not alter gallbladder or hepatic bile lithogenic index. Two of five 28-day TPN animals developed biliary sludge, and one of these animals formed pigment gallstones. TPN without lipid decreased serum cholesterol concentration. As the lipid concentration of the TPN solution was increased, serum cholesterol increased. These data indicate that TPN induces gallbladder stasis regardless of caloric source but does not increase bile lithogenic index despite a dose-related rise in serum cholesterol as the percent of calories provided as lipid is increased. We conclude that TPN-induced gallbladder disease results from gallbladder stasis and not from increased bile cholesterol saturation.
Ex vivo recirculation perfusion preparations of the canine pancreas are useful for the study of pancreatic physiology and exocrine secretory function. Vagaries of isolated ex vivo organ perfusion, however, require a thorough familiarity with available circulation media and component technology. Electrolyte and acid-base homeostasis can be facilitated by incorporating a dialysis unit into the perfusion circuit. Viability of the preparation is best assessed by constancy of vascular resistance and oxygen extraction during the period of perfusion. Limitations imposed by this closed method of organ perfusion on studies of pancreatic endocrine function and on duodenopancreatic hormonal interactions (enteroinsular axis) must be recognized.
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