The use of large domestic animals as heart donors represents a potential solution to the current human donor shortage. Hyperacute graft rejection (HAR) remains a major barrier to xenotransplantation. The purpose of this study was to employ an ex-vivo preparation for the evaluation of HAR in discordant cardiac xenografts. Freshly excised hearts from thirty-nine pigs (10-37kg) were perfused at 37 degrees centigrade via the aorta in a retrograde fashion. The hearts were allowed to function in a non- working mode for four hours or until the rejection process resulted in irreversible cardiac dysfunction. The perfusate consisted of Krebs-Henseleit bicarbonate buffer in addition to fresh whole autologous pig blood(n=4) (Group A), dog blood(n=3) (Group B), baboon blood(n=5) (Group C), human PRBCs (n=2) (Group D), human blood and plasma (n=3) (Group E), human whole blood (n=lO) (Group F), and human plasma(n=9) (Group G). HAR was uniform for Groups B, E, and G. No evidence of HAR was noted in Groups A, C, or D. Two of ten hearts demonstrated HAR in Group F. This perfusion circuit provides a means for the analysis of each component of human blood in order to define which components are required for HAR of discordant cardiac xenografts. The results indicate that the HAR of pig hearts perfused with human blood is mediated by some component found in the plasma, most probably pre-formed natural antibody. Studies are currently underway to evaluate which class of antibody mediates the rejection process.
