Heart allograft endothelial cell dysfunction. Cause, course, and consequences

Allograft coronary endothelial cells can serve as potent stimulators (antig en-presenting cells) as well as targets of allogeneic lymphocyte reactivity . Independent of the cause leading to endothelial cell injury after transpl antation, endothelial cell activation and dysfunction occurs, associated wi th modification in endothelial cell-dependent molecule expression. The prevalence of coronary endothelial vasomotor dysfunction is approximate ly 20-30 % during the first year, and 30-40 % in the long-term follow-up. I mportantly, no association is detectable between endothelial dysfunction an d intimal thickness, suggesting two distinct entities of allograft vasculop athy. Early predictors of vasomotor dysfunction are proinflammatory cytokin es and endothelin expression. Repetitive subendocardial ischemia during myo cardial stress (due to microvasular dysfunction) may result in an impairmen t of left ventricular function. In non-transplant patients coronary endothe lial dysfunction predicts cardiac events during long-term follow-up. It is reasonable that early administration of endothelial-protective compounds is necessary for protection of allograft endothelial dysfunction and vasculop athy during follow-up. The explanted donor heart may offer a potential for gene therapy techniques including modification of allograft phe notype and modulation of the host alloimmune response. Other protective strategies may include improvement of cardioplegic solutions and reperfusion strategies, recovery of the imbalance between vasoactive mediators, and treatment with HMG-CoA-reductase inhibitors and/or ACE inhibitors.