The dependence of hepatic function upon sufficient oxygen supply during prolonged isolated rat liver perfusion

It is unclear how the omission of a perfusate oxygen carrier may influence data derived from prolonged in vitro liver perfusions. The effects of reduced perfusate oxygen content upon liver function tests conducted in livers from male Sprague-Dawley rats perfused for 6 h, were studied using diluted rat blood (PCV = 10%) (group 1) and compared to lines perfused with Krebs' buffer (group 2). Perfusate and bile samples were withdrawn at the start and at hourly intervals following the commencement of perfusion for biochemical analysis of aspartate-serine transaminase, alkaline phosphatase, bilirubin, urea and potassium concentrations, and also for perfusate gas measurements for calculations of hepatic oxygen uptake. There were no significant differences between the initial perfusion pressures of 11.4 +/- 1.6 and 15.7 +/- 2.4 mm Hg at the start of perfusion (group 1 versus group 2, respectively). Maintenance of comparable perfusion pressures at the start of perfusion, however, resulted in a significant difference in the fixed flow rate between the two groups of 1.9 +/- 0.1 and 2.6 +/- 0.2* ml/min/g liver and resulted in significantly higher perfusion pressures in group 2 than in group 1 after 6 h of perfusion (18.2 +/- 2.0 versus 8.7 +/- 1.7 mmHg, respectively). Bile volume production was significantly greater in group 1 than in group 2, at 784 +/- 84 vs 458 +/- 75 mu l/h** respectively. Hepatic oxygen uptake (HOU) was significantly greater in group 1 than in group 2, and maximal at 0.93 +/- 0.13 vs 0.32 +/- 0.08** mu mol/min/g, respectively. Bile concentrations of bilirubin and potassium were significantly greater in group 1 than in group 2, 23.0 +/- 0.6 vs 4.9 +/- 0.4 mu mol/l*** and 4.7 +/- 0.5 vs 1.1 +/- 0.2 mmol/l**, respectively. Perfusate concentrations of urea, bilirubin, and glucose were significantly higher in group 1 than group 2, 5.7 +/- 0.5 versus 1.4 +/- 0.2 mu mol/l**; 2.4 +/- 0.5 versus 0.7 +/- 0.1 mu mol/l** and 22.1 +/- 1.4 versus 17.8 +/- 0.9 mu mol/l***. It is concluded that in vitro perfusion of the rat liver with Krebs'-Henseleit buffer (KHB) via the portal vein alone may be insufficient to maintain optimum liver function as assessed by the tests used. Inclusion of a perfusate oxygen carrier is optimal if livers are to be perfused at physiological pressures. *p < 0.05; **p < 0.01; ***p < 0.001; group 1 versus group 2, Student's unpaired t test. (C) 1998 Elsevier Science Inc.