Uptake and excretion of sodium taurocholate by the isolated perfused neonatal sheep liver

We present a model for perfusion of the isolated perfused neonatal sheep liver which allows examination of drug disposition by the intact organ. We studied the disposition of sodium taurocholate (TC) in seven neonatal lambs (ages 2-11 days) and compared the results with earlier data from the perfused fetal sheep liver (Ring, J. A. et al. Biochem. Pharmacol. 1994, 48, 667-674). Measurements of perfusion pressure, oxygen consumption, lactate:pyruvate ratio, bile flow, and liver histology indicated that the preparation was both viable and stable over a 2 h period. [14C]-labeled TC was added to the reservoir by constant infusion (30 micromol/h) and the ductus venosus shunt quantitated by injection of [153Gd]-labeled microspheres. Shunt-corrected hepatic extraction ratio of TC was 0. 56 +/- 0.14 (fetal 0.23 +/- 0.16, p < 0.005) and clearance of TC was 0.92 +/- 0.35 mL/min/g liver (fetal 0.44 +/- 0.23 mL/min/g, p < 0. 01). We conclude that the isolated perfused neonatal sheep liver is a useful experimental model which will facilitate the study of the developmental physiology and pharmacology of the liver. There is considerable maturation of the biliary excretion of TC between the late fetal and early neonatal periods in the lamb.