SUCCESSFUL LONG-TERM XENOPERFUSION OF THE PIG-LIVER - CONTINUOUS ADMINISTRATION OF PROSTAGLANDIN E(1) AND INSULIN

For clinical utilization of extracorporeal liver perfusion as an artif icial liver assist device, we examined the possibility of long-term xe noperfusion of the pig liver by the continuous administration of prost aglandin E(1) (PGE(1)) and insulin. After a 3-hr perfusion period, pig livers that were xenoperfused with human blood exhibited a drastic de crease in the perfusate volume, a progressive elevation of the hepatic artery pressure, a gradual deterioration of bile production, and a ma rked increase in the release of creatine kinase-BB component. The cont inuous administration of PGE(1) (25 mu g/hr) and insulin (1 U/hr) sign ificantly improved these derangements (P<0.05) and allowed stable perf usion for up to 9 hr. This manipulation also inhibited leukocyte aggre gation in the graft, the characteristic perfusate hemolysis, and accel eration of ketogenesis. Histological examination revealed that the int erlobular edema and hemorrhage, characteristics of tissue injuries in xenogeneic hyperacute rejection, were markedly alleviated in the PGE(1 ) and insulin-treated group. This study clarifies the finding that the combined administration of PGE(1) and insulin is effective for long-t erm xenogeneic extracorporeal liver perfusion, with the graft viabilit y well maintained.