Influence of nicardipine on post-hypoxic injury in the isolated perfused rat liver

We investigated microcirculatory changes and hepatocellular injury due to hypoxia/reoxygenation and the effects of nicardipine, a calcium channel blocker, using the isolated perfused rat liver technique. Liver perfusion was carried out in three consecutive phases: 30-min pre-hypoxia perfusion, 120-min hypoxia perfusion and 30-min reoxygenation perfusion in two groups, a control (n = 5) group and a nicardipine group (n = 5). In the nicardipine group, nicardipine (2 x 10(-6) M) was added to the perfusate prior to the hypoxia perfusion. Intrahepatic volumes, sinusoidal volume and extravascular volume accessible to albumin, were assessed by the multiple indicator dilution technique. Though 120-min hypoxia per se caused only a slight increase in the lactate dehydrogenase (LDH) release and no significant alterations in perfusion pressure and intrahepatic volumes, reoxygenation elicited hepatocellular injury assessed by the LDH level in the perfusate along with a substantial increase in perfusion pressure and an increase in extravascular volume. Nicardipine pretreatment attenuated the increase in LDH level, perfusion pressure and intrahepatic volumes after reoxygenation, but there were no difference in liver microcirculation during 120-min hypoxia. The data of the current study emphasized the crucial role of Ca2+ influx in hypoxic/reoxygenation hepatocellular injury and suggested that a direct vasodilating effect of nicardipine on the intrahepatic vasculature during hypoxia is unlikely as the mechanism for its cytoprotective effects.