EFFECT OF CONTINUOUS COMPLEMENT INHIBITION USING SOLUBLE COMPLEMENT RECEPTOR-TYPE-1 ON SURVIVAL OF PIG-TO-PRIMATE CARDIAC XENOGRAFTS

A single bolus of soluble complement (C) receptor type 1 (sCR1, TP-10) has been shown to delay hyperacute rejection (HAR) of porcine cardiac xenografts (Xgs) by primate recipients, In these recipients, C activi ty slowly returned and C deposition was noted in the Xgs at rejection, To evaluate the effect of sustained C inhibition using sCR1 on HAR, t wo additional cynomolgus monkeys received porcine cardiac Xgs and a co ntinuous infusion of sCR1, In the first recipient, Xgs survival was 5 days (120+ hr), whereas in the second, Xg survival was 7 days (168(+) hr). Serial biopsies of the Xgs were remarkable for an increasing cell ular infiltrate composed predominantly of neutrophils and macrophages, and the development of edema, hemorrhage, and myocyte necrosis, These findings suggest that once C-mediated HAR has been inhibited, infiltr ation of the Xg by these cells may lead to accelerated acute rejection , which is an additional barrier to successful longer term Xg survival .