Attenuation of ischemic liver injury by prostaglandin E1 analogue, misoprostol, and prostaglandin I2 analogue, OP-41483

Background: Prostaglandin has been reported to have protective effects against liver injury. Use of this agent in clinical settings, however, is limited because of drug-related side effects. This study investigated whether misoprostol, prostaglandin E-1 analogue, and OP-41483, prostaglandin I-2 analogue, which have fewer adverse effects with a longer half-life, attenuate ischemic liver damage. Study Design: Thirty beagle dogs underwent 2 hours of hepatic vascular exclusion using venovenous bypass. Misoprostol was administered intravenously for 30 minutes before ischemia and for 3 hours after reperfusion. OP-41483 was administered intraportally for 30 minutes before ischemia (2 mu g/kg/min) and for 3 hours after reperfusion (0.5 mu g/kg/min). Animals were divided into five groups: untreated control group (n = 10); high-dose misoprostol (total 100 mu g/kg) group (MP-H, n = 5); middle-dose misoprostol (50 mu g/kg) group (MP-M, n = 5); low-dose misoprostol (25 mu g/kg) group (MP-L, n = 5); and OP-41483 group (OR n = 5). Animal survival, hepatic tissue blood flow (HTBF), liver function, and histology were analyzed. Results: Two-week animal survival rates were 30% in control, 60% in MP-H, 100% in MP-M, 80% in MP-L, and 100% in OP. The treatments with prostaglandin analogues improved HTBE and attenuated liver enzyme release, adenine nucleotrides degradation, and histologic abnormalities. In contrast to the MP-H animals that exhibited unstable cardiovascular systems, the MP-M, MP-L, and OP animals experienced only transient hypotension. Conclusions: These results indicate that misoprostol and OP-41483 prevent ischemic liver damage, although careful dose adjustment of misoprostol is required to obtain the best protection with minimal side effects. (J Am Coll Surg 1998;187:276-286. (C) 1998 by the American College of Surgeons)