EFFECTS OF TOTAL PARENTERAL NUTRTTION (TPN) CN BILIARY FUNCTION IN RAPIDLY GROWING RATS

Abstract

The cholestatic effects of TPN in early infancy are well documented, whereas little is known about the influence of TPN on bile flow and bile acid output in growing children. Unrestrained actively growing rats weighing 50±4g (Y) and non-growing mature rats weighing 225±8g (A) were kept on TPN for 8 days with fluids containing 4.0% amino acids, 27.5% dextrose, minerals, vitamins, and trace metals. Controls were on standard chow or fed via gastrotomy using the nutrient solution. In each subgroup (3-5 rats), the study was terminated with a 150 min collection of bile obtained in 15 min aliquots from the common bile duct. All Y gained at least 20% B.W. during the 8 days; weight in all A was stable. Bile flow (μl/h/100g), biliary bile acid concentrations (mM), and bile acid output (mM/h/100g) were comparable in control and TPN-treated A. In Y controls compared with A, bile flow was greater (773±90 vs 298±45) and bile acid concentrations higher (45±7 vs 29±5), resulting in 3-4 fold greater bile acid output in Y. In striking contrast with A, bile flow was reduced 38% (p<0.004) and biliary bile acid concentration decreased 33% (p<0.002) in Y on TPN, causing bile acid output to decline from 35.6±11.4 to 14.8±2.6. Conclusions: Bile flow and bile acid output are greater in Y than in A. TPN has no effect on these functions in A detectable after 8 days, while both bile flow and biliary bile acid concentrations are reduced in Y. Thus, growing rats secrete more bile and bile acids, and are susceptible to cholestasis from TPN.