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 li ver which allows examination of drug disposition by the intact organ. We st udied the disposition of sodium taurocholate (TC) in seven neonatal lambs ( ages 2-11 days) and compared the results with earlier data from the perfuse d fetal sheep liver (Ring, J. A. et at. Biochem. Pharmacol. 1994, 48, 667-6 74). Measurements of perfusion pressure, oxygen consumption, lactate:pyruva te ratio, bile flow, and liver histology indicated that the preparation was both viable and stable over a 2 h period. [C-14]-labeled TC was added to t he reservoir by constant infusion (30 mu mol/h) and the ductus venosus shun t quantitated by injection of [Gd-153]-labeled microspheres. Shunt-correcte d 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 neonata l sheep liver is a useful experimental model which will facilitate the stud y of the developmental physiology and pharmacology of the liver. There is c onsiderable maturation of the biliary excretion of TC between the late feta l and early neonatal periods in the lamb.