Augmented portal flow in the isolated perfused cirrhotic rat liver: a haemodynamic and morphological study

Abstract

1. Isolated perfused cirrhotic rat livers were used to study the effects of an increase in portal perfusion pressure and portal flow on the microcirculation and viability of the hepatocytes. Cirrhosis was induced by CCl4, and Krebs-Ringer bicarbonate buffer solution was used as the perfusate. Portal perfusion pressures were increased incrementally between 25 and 45 cm H2O. The viability of the livers was assessed and histological studies were performed under light and electron microscopy. 2. An increase in portal perfusion pressure induced an increase in hepatic flow in all the experiments (P < 0.05). Hepatic flow was 2.52 ml min−1 g−1 of liver (SD 0.67; n = 5) at basal pressure compared with 4.19 ml min−1g−1 of liver (SD 0.93; n = 5) and 5.91 ml min−1g−1 of liver (SD 0.63; n = 5) when pressures were raised to 25 and 45 cm HzO, respectively. Portal perfusion pressure and hepatic flow were correlated (r = 0.908; P < 0.001; n = 30). 3. Production of the enzyme alanine aminotransferase (EC 2.6.1.2) increased significantly from 5.69 i.u. ml−1min g-l of liver (SD 3.62; n = 5) to 23.53 i.u. ml−1min g−1 of liver (SD 16.7; n = 5) when the perfusion pressure was raised from baseline to 30 cm H2O. In all the cases the porto-caval gradient of enzyme production was within the normal range. No correlation existed between the release of enzyme and portal perfusion pressures 4. Histological studies demonstrated sinusoidal dilatation in one case out of five in the control group compared with nine cases out of 25 in the high perfusion pressure groups. Dead sinusoidal cells coloured by Trypan Blue were observed in one case out of five in the control group compared with nine cases out of 25 in the high perfusion pressure groups. With electron microscopy, occasional lesions such as detachment of endothelial cells or blebs were found. No relationship existed between portal perfusion pressures and histological lesions. 5. This study shows that a brief increase in portal perfusion pressure in the isolated perfused cirrhotic rat liver induces an increase in hepatic flow without a change in the viability of the liver and without significant histological alterations.