PREVENTION OF HYPERACUTE REJECTION BY HUMAN DECAY-ACCELERATING - FACTOR IN XENOGENEIC PERFUSED WORKING HEARTS

As a potential source of organs for xenotransplantation, pigs that are transgenic for human decay accelerating factor (DAF) have been bred i n order to overcome hyperacute rejection. We investigated the protecti ve effect of human DAF in a porcine working heart model perfused by hu man blood. Hearts of normal landrace pigs served as controls, The foll owing parameters were measured: stroke work index, coronary flow and a rteriovenous oxygen consumption, 6-keto prostaglandin F-1 alpha and pr ostaglandin E(2) as markers of endothelial cell activation; creatine p hosphokinase and lactate dehydrogenase for evaluation of the extent of myocardial damage; TNF alpha and IL-6 as markers of mononuclear cell activation, Histological and ultrastructural investigations from myoca rdial tissue sections were done at the end of perfusion, Human (h) DAF appeared to inhibit complement-mediated endothelial cell activation o f transgenic pig hearts successfully. This was in contrast to landrace pig hearts, which had a sixfold increase of prostaglandin levels duri ng perfusion with human blood, The cardiac weight increase during perf usion time due to interstitial edema tended to be less in the hDAF gro up. Myocardial damage was minimal in transgenic hearts, whereas normal pig hearts produced a threefold increase of creatine phosphokinase an d lactate dehydrogenase levels. In these hearts, electron microscopy r evealed single cell necrosis of myocytes and vacuolization of mitochon dria with cristae rupture. According to the results obtained in the wo rking heart model, the breeding of pigs that are transgenic for hDAF r epresents a promising step to making heart xenotransplantation a clini cal reality in the future.