THE CONTRIBUTION OF ENDOTHELIAL-CELLS TO HYPERACUTE REJECTION IN XENOGENEIC PERFUSED WORKING HEARTS

The mechanisms leading to the hyperacute rejection of a vascularized x enograft are still incompletely understood. The first stage of the rej ection process is when blood of the recipient comes into contact with the endothelium of the xenograft. A working heart model was used to ex amine endothelium-related processes and their impact on organ function . Pig hearts were perfused with porcine (autologous) or human (xenogen eic) blood. Cardiac function was evaluated by calculating the stroke w ork index, arteriovenous oxygen, coronary flow, and resistance. PgF1a as a marker of endothelial activation, its antagonist TXB(2), and myog lobin reflecting myocardial damage were measured in the hemoperfusate. H&E and PAS staining and immunohistological demonstration of factor V III-related antigen was performed. Xenogeneic perfused porcine hearts showed significantly less stroke work, a higher arteriovenous oxygen d ifference, and an increased coronary resistance. Factor VIII-related a ntigen could not be demonstrated immunohistologically on the endotheli um after xenogeneic perfusion. PgF1a levels were significantly higher in the xenogeneic hemoperfusate, indicating endothelial cell activatio n. The concentration of myoglobin in the hemoperfusate remained within normal values and was similar during autologous and xenogeneic perfus ion. Therefore endothelium-related processes are likely to affect the coronary circulation-thus being one mechanism leading to diminished ca rdiac performance during hyperacute rejection.