title: Successful long-term xenoperfusion of the pig liver: continuous administration of prostaglandin E1 and insulin.
abstract: For clinical utilization of extracorporeal liver perfusion as an artificial liver assist device, we examined the possibility of long-term xenoperfusion of the pig liver by the continuous administration of prostaglandin E1 (PGE1) and insulin. After a 3-hr perfusion period, pig livers that were xenoperfused with human blood exhibited a drastic decrease in the perfusate volume, a progressive elevation of the hepatic artery pressure, a gradual deterioration of bile production, and a marked increase in the release of creatine kinase-BB component. The continuous administration of PGE1 (25 microg/hr) and insulin (1 U/hr) significantly improved these derangements (P<0.05) and allowed stable perfusion for up to 9 hr. This manipulation also inhibited leukocyte aggregation in the graft, the characteristic perfusate hemolysis, and acceleration of ketogenesis. Histological examination revealed that the interlobular edema and hemorrhage, characteristics of tissue injuries in xenogeneic hyperacute rejection, were markedly alleviated in the PGE1 and insulin-treated group. This study clarifies the finding that the combined administration of PGE1 and insulin is effective for long-term xenogeneic extracorporeal liver perfusion, with the graft viability well maintained.
authors.affiliation: Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Terajima
authors.forename: Y
authors.initials: Y
authors.lastname: Shirakata
authors.forename: T
authors.initials: T
authors.lastname: Yagi
authors.forename: S
authors.initials: S
authors.lastname: Mashima
authors.forename: H
authors.initials: H
authors.lastname: Shinohara
authors.forename: S
authors.initials: S
authors.lastname: Satoh
authors.forename: Y
authors.initials: Y
authors.lastname: Arima
authors.forename: T
authors.initials: T
authors.lastname: Gomi
authors.forename: T
authors.initials: T
authors.lastname: Hirose
authors.forename: R
authors.initials: R
authors.lastname: Takahashi
authors.forename: I
authors.initials: I
authors.lastname: Ikai
authors.forename: T
authors.initials: T
authors.lastname: Morimoto
authors.forename: T
authors.initials: T
authors.lastname: Inamoto
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaoka
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001646:Bile / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007958:Leukocyte Count; D019164:Liver, Artificial; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D013552:Swine
chemical_list: D007328:Insulin; D000527:Alprostadil