PROLONGED DISCORDANT CARDIAC XENOGRAFT SURVIVAL IN NEWBORN RECIPIENTS

Background We previously demonstrated very low levels of xenoreactive natural antibodies in newborns, suggesting the possibility of prolonga tion of xenograft survival in newborn recipients. We used a pig-to-new born goat heterotopic cardiac xenograft model to examine our hypothesi s that hyperacute rejection would be absent in newborn recipients and that both humoral and cellular rejection would participate in the late phase of discordant xenograft rejection. Methods and Results The seru m of newborn goats was found to have very low titers of natural anti-p ig antibodies. Newborn pig hearts were transplanted heterotopically in to the neck of four unmanipulated newborn goats: none of these xenogra fts underwent hyperacute rejection. Dilation of the xenografts and dec reased contractility were observed 4 to 6 days after transplantation, and the xenografts eventually ceased functioning between 6 and 8 days after transplantation. Blood samples collected after transplantation d emonstrated a dramatic increase in anti-pig xenoantibody titers and co rrelated with histological studies demonstrating features consistent w ith delayed humoral rejection, including reactive vascular endothelial and perivascular stromal cells, marked capillary congestion, and inte rstitial hemorrhages. Scant to diffuse perivascular and interstitial i nfiltration of activated lymphoid cells occurred. Conclusions Our stud y demonstrates that hyperacute rejection does not occur, allowing limi ted prolongation of xenograft survival in a pig-to-newborn goat cardia c xenograft model. We propose that this is attributable, at least in p art, to the very low titers of natural antibodies in newborn recipient s. Delayed xenograft rejection, however, remains an important problem in these newborn recipients. This delayed xenograft rejection is likel y the result of both humoral and cellular rejection mechanisms.