Expression of endothelial adhesion molecules and thrombomodulin in cardiac transplantation

Abstract

Objective: To describe the pattern of endothelial cell activation (ECA) in the transplanted human heart. Methods: 39 donor hearts had trucut biopsies from the right (RV) and the left ventricles (LV) at: initial assessment of the donor, end of warm ischaemia and after 10 min. of reperfusion. In addition, heart transplant patients had follow up RV biopsies during rejection surveillance at 1 week, 1 month and 3 months postoperatively. Biopsies exhibiting rejection were excluded from the analysis. 6 of the patients were cystic fibrosis domino donors. Another 9 patients undergoing routine cardiac surgery served as controls. Psel, VCAM-1, Esel and thrombomodulin (Thr) were examined by immunohistology. Results: There was no difference between the RV and the LV at any of the intraoperative time points, but important time-dependent variations were seen. Psel, and VCAM-1 (but not Esel) are upregulated in brain-dead and in domino donors (p 0.01 for LV and p 0.005 for RV). Thr is reduced at the baseline in all hearts used for transplantation, and the depletion accentuates postoperatively (p 0.30 for LV and p 0.02 for RV). Psel is present in 85% of vessels throughout transplantation and decreases to cca. 60% post-transplant (p 0.001). VCAM-1 is present in 20% of vessels initially, decreases to 5% during storage (this fall is inversely correlated to the ischaemic time), increases to 47% at reperfusion and gradually decreases thereafter (p 0.001). Esel expression increases progressively from 15% initially to 45% at reperfusion and decreases postoperatively (p 0.001). Patients with donor organ failure did not have any specific pattern of ECA. However, there was a trend towards accumulation of clinical risk factors in this group. Recipients of aprotinin had reduced expression of Esel and VCAM-1 in the LV at reperfusion. Conclusion: Cardiac transplantation (including domino) is associated with marked ECA changes, with no difference between the two ventricles. The changes persist in the postoperative period even in the absence of rejection. Expression of ECA markers is influenced by aprotinin but is not predictive of donor organ failure.