Prolongation of guinea pig-to-rat xenograft survival with BN 52063, a specific antagonist of platelet-activating factor.
Xenotransplantation between different species may possibly solve some of the difficulties associated with human donor organ availability. However, organ xenografts are very rapidly rejected, particularly in discordant donor-recipient combinations, due to the presence of natural cytotoxic antibodies in the recipient. The purpose of this study was to evaluate the efficacy of two potential inhibitors of a xenogeneic antigen-antibody reaction: Iloprost, an analogue of prostacyclin I2, and BN 52063, a PAF-antagonist. Heart (group A) or liver (group B) transplantations were performed in the guinea pig-to-Lewis rat donor-recipient combination. Fifteen minutes prior to revascularization of the graft an intravenous infusion was instituted using saline (0.01 ml/min) (groups A1 and B1), saline and dimethylsulfoxide (DMSO, 0.1 ml/min) (groups A2 and B2), Iloprost (2 ng/Kg/min) (groups A3 and B3) or BN 52063 (6 mg/Kg/min) (groups A4 and B4). Heart graft survival times (min) were 12.3 +/- 1.7 (A1), 13.4 +/- 2.2 (A2), 14.8 +/- 1.0 (A3), 18.3 +/- 1.4 (A4). Liver graft survival times (min) were 158.4 +/- 38.9 (B1), 129.6 +/- 14.4 (B2), 168.1 +/- 18.0 (B3) and 306.2 +/- 36.5 (B4). A significant prolongation (p less than 0.05) was observed in group A4 versus A1, A2, A3 and in group B4 versus B1, B2, B3. These results suggest that prevention of xenograft rejection using PAF-antagonist in association with other methods should be further investigated.
Filipponi
F
F
Laboratoire de Recherche Chirurgicale, Clinique Chirurgicale de l'Hôpital Cochin, Paris.
Michel
A
A
Houssin
D
D
D000818:Animals; D011464:Epoprostenol / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects*; D006168:Guinea Pigs; D016027:Heart Transplantation; D016285:Iloprost; D007783:Lactones; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D009206:Myocardium / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic
D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; C050422:BN 52063; D011464:Epoprostenol; D016285:Iloprost