Beneficial actions of two novel calcium entry blockers in the isolated perfused hypoxic cat liver.

The effects of two new calcium entry blockers, anipamil and ronipamil, were studied during 150 min of normoxic or hypoxic perfusion in isolated perfused cat livers. Hypoxic livers in which the vehicle for these inhibitors (i.e., ethanol) was injected intravenously prior to isolation of the liver, exhibited significantly higher increases in perfusion pressure, perfusate lactate dehydrogenase and cathepsin D activities, compared to control normoxic perfused livers. In contrast, the livers isolated from cats pretreated with calcium entry blocker anipamil and subsequently perfused under hypoxic conditions showed no significant difference in any of these variables from the control normoxic perfused livers. Ronipamil given intravenously 30 minutes prior to isolation also significantly protected the liver during hypoxia. The protection afforded by anipamil and ronipamil appears to be related to their inhibition of Ca++ influx which has been linked to cell death in hepatocytes.