Premium
Preconditioning with the prostacyclin analog epoprostenol and cobra venom factor prevents reperfusion injury and hyperacute rejection in discordant liver xenotransplantation
Author(s) -
Meyer zu Vilsendorf Andreas,
Link Claudia,
Jörns Anne,
Nagel Eckhard,
Köhl Jörg
Publication year - 2001
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1034/j.1399-3089.2001.00074.x
Subject(s) - xenotransplantation , prostacyclin , liver transplantation , medicine , guinea pig , pharmacology , reperfusion injury , transplantation , immunology , ischemia
Liver xenografts transplanted from guinea pig to rat suffer from inadequate organ reperfusion and initial dysfunction, despite sufficient complement depletion using cobra venom factor (CVF). Reperfusion injury is prevented when complement depleted donors are treated with the prostacyclin analog epoprostenol. Histological analysis suggests that epoprostenol preconditioning prevents post‐reperfusion spasms of the intrahepatic branches of the portal vein and strongly reduces appearance of hepatocyte apoptosis shortly after transplantation. Cobra‐venom‐treated rats show breakdown of glucose metabolism and die in acute hypoglycaemia, whereas the additional application of epoprostenol restores gluconeogenesis. Consequently, recipient survival after epoprostenol and CVF treatment is significantly improved compared with animals receiving CVF only (5.1 ± 2.6 h vs. 17.9 ± 5.1 h). These data demonstrate that initial dysfunction of discordant liver grafts in the guinea‐pig‐to‐rat species combination, can be overcome by the application of epoprostenol combined with CVF. Using this pharmacologic regimen, the discordant guinea‐pig‐to‐rat model appears useful to study further questions concerning functional and immunological compatibility of a discordant liver xenograft.