Uridine regulation by the isolated rat liver: perfusion with an artificial oxygen carrier

Abstract
The isolated rat liver was used to investigate the role of the liver in the regulation of circulating uridine concentrations. A synthetic blood substitute (Fluosol-43) was utilized as an alternative O2-carrying perfusion medium to a simplified blood preparation and produced no apparent hepatotoxicity within the perfusion period. The isolated rat liver excreted uridine into a circulating perfusion medium achieving concentrations similar to those found in rat plasma (1.4 .+-. 0.6 .mu.M). The mean output of uridine over 2 h was 107 nmol.cntdot.h-1.cntdot.g liver-1, but if the perfusate was recirculated the net output of uridine was reduced to 12.7 nmol.cntdot.h-1.cntdot.g-1. The rate of depletion of nonphysiological concentrations of circulating uridine was concentration dependent up to 25 .mu.M. At a steady state of circulating uridine, a radioactive uridine spike was cleared with a t1/2 of 7.4 min and an elimination constant of 0.094 min-1; 30% of the radioactivity appeared in the perfusate as metabolites of uridine within 40 min. Thus the perfused rat liver acts to maintain circulating uridine concentrations similar to those measured in plasma.