Prolonged discordant cardiac xenograft survival in newborn recipients

We previously demonstrated very low levels of xenoreactive natural antibodies in newborns, suggesting the possibility of prolongation of xenograft survival in newborn recipients. We used a pig-to-newborn goat heterotopic cardiac xenograft model to examine our hypothesis 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.

The serum of newborn goats was found to have very low titers of natural anti-pig antibodies. Newborn pig hearts were transplanted heterotopically into the neck of four unmanipulated newborn goats: none of these xenografts underwent hyperacute rejection. Dilation of the xenografts and decreased 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 demonstrated a dramatic increase in anti-pig xenoantibody titers and correlated with histological studies demonstrating features consistent with delayed humoral rejection, including reactive vascular endothelial and perivascular stromal cells, marked capillary congestion, and interstitial hemorrhages. Scant to diffuse perivascular and interstitial infiltration of activated lymphoid cells occurred.

Our study demonstrates that hyperacute rejection does not occur, allowing limited prolongation of xenograft survival in a pig-to-newborn goat cardiac xenograft model. We propose that this is attributable, at least in part, to the very low titers of natural antibodies in newborn recipients. Delayed xenograft rejection, however, remains an important problem in these newborn recipients. This delayed xenograft rejection is likely the result of both humoral and cellular rejection mechanisms.