HEPATOPROTECTION BY A PGI(2) ANALOG IN COMPLETE WARM ISCHEMIA OF THE PIG-LIVER - PROSTANOID RELEASE FROM THE REPERFUSED LIVER

We examined the hepatoprotective effect of a prostaglandin (PG)I-2 ana logue by analyzing the endogenous release of prostanoid from the pig l iver. Fourteen female pigs underwent 1 hr complete hepatic vascular ex clusion (HVE); the portal and vena caval circulation was actively deco mpressed. The animals were divided into one of two groups (n=7, each) according to pretreatment with the prostacyclin analogue (OF 2507, OF) administered via a mesenteric vein branch for 30 min at a rate of 2 m u g/kg/min immediately prior to HVE. The plasma levels of prostaglandi n E(2) (PGE(2)), 6-keto-prostaglandin F-1-alpha (6-keto-PGF(1a)), and thromboxane B-2 (TXB(2)), from the blood samples from the aorta, the h epatic vein, and the portal vein were serially compared for 60 min aft er the restoration of blood flow. Other parameters included 7-day surv ival rate, serum biochemistry, and endo toxin assay. A significant imp rovement in 7-day survival rate (6/7 vs. 1/7 for the control, P<0.02) was observed in the OF-treated animals, associated with amelioration o f serum transaminase activities but with no differences in plasma endo toxin levels. The reperfused liver progressively and substantially rel eased PGE(2) but did not generate other prostanoids (TXB(2) and 6-keto -PGF(1 alpha)). OP pretherapy substantially suppressed hepatic generat ion of the PGE(2) postreflow, correlating with serum transaminase leve ls (r(8)=0.80; P<0.01, at 60 min). We conclude that the PGI(2) analogu e ameliorates hepatic ischemia/reperfusion injury by down-regulating P GE(2) production from the reperfused liver.