Human plasma causes rapid dysfunction in ex vivo pig hearts

The use of hearts from large domestic animals represents a potential solution to the current human donor shortage. However, xenogeneic hyperacute graft rejection remains a major barrier to xenotransplantation. The purpose of this study was to use an ex vivo preparation to study variables that may correlate with hyperacute rejection in cardiac xenografts. Freshly excised hearts from 37 anesthetized pigs (10 to 37 kg) were perfused at 37 degrees C through the aorta with retrograde flow. The hearts functioned in a nonworking mode for 4 hours or until irreversible cardiac dysfunction occurred. Various perfusates were used: fresh whole autologous pig blood (n = 4), dog blood (n = 3), baboon blood (n = 5), human packed red blood cells (n = 2), human whole blood (n = 10), human whole blood and plasma (n = 3), and human plasma (n = 9), to which a modified Krebs-Henseleit bicarbonate buffer solution was added. Rapid loss of function was uniform and occurred most quickly (13 to 18 minutes) for hearts perfused with dog blood and human plasma. Isolated cardiac perfusion provided a means for the analysis of the cellular and plasma components of human blood to define which were required for rapid loss of function. The results indicated that the reaction was mediated by components present only in plasma.