Effects of double-filtration plasmapheresis and a platelet-activating factor antagonist on the prolongation of xenograft survival.

Xenotransplantation may be considered a possible solution to the clinical donor-organ shortage. We studied the effects of the removal of preformed natural antibodies against donor tissue by double-filtration plasmapheresis (DFPP) and the administration of a platelet-activating factor antagonist on the prolongation of xenograft survival using the pig-to-dog model. The porcine hearts were perfused with the blood of mongrel dogs. Pairs of animals were divided into four groups: group I (n = 3) was given no pretreatment before perfusion; group II (n = 6) was pretreated by DFPP; group III (n = 3) was given a platelet-activating factor antagonist intravenously at a dose of 0.1 mg/kg 5 minutes before and after perfusion; group IV (n = 5) was pretreated by DFPP and then given a platelet-activating factor antagonist. The titer of natural antibodies was measured by lymphocytotoxicity and hemagglutination. Heart specimens were examined by immunohistochemical staining for deposits of dog antibodies. No immunosuppressive drugs were given in this study. The porcine hearts resumed beating immediately after perfusion in all groups. The mean duration of the graft beating was 17.0 +/- 2.0 minutes for group I, 215.2 +/- 22.6 minutes for group II (p < 0.001 compared with group I), 18.3 +/- 2.1 minutes for group III, and 317.0 +/- 26.5 minutes for group IV (p < 0.001 compared with group II). Immunoglobulin (Ig) M, IgG, complements (C3, C4), and fibrinogen were removed significantly from the perfusing blood, and natural antibody titer was scarcely detectable in groups II and IV after DFPP.(ABSTRACT TRUNCATED AT 250 WORDS)