Dopamine derivate N-octanoyl-dopamine: a novel concept for conditioning of the donor heart

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Heart transplantation became the most effective treatment for end-stage heart disease. Worsened donor shortage and increased number of patients waiting for transplants is limiting this procedure. Donors after brain death are presently the only reliable source for cardiac transplants. However, hemodynamic instability and cardiac dysfunction have been demonstrated in brain-dead donors and this could also affect the graft function after heart transplantation. One of the potential strategies to improve donor organ function and protect allografts against hypothermic preservation/reperfusion injury is the preconditioning. It has been shown that low dose dopamine treatment of the potential organ donor may improve early graft function and survival after heart and kidney transplantation. As the routine use of dopamine might be precluded by its possible side effects (tachycardia, hypertensive crisis), a novel dopamine analog N-octanoyl dopamine has been developed lacking any effects on dopamine receptors and thereby any hemodynamic action. The main aims of the present proposal is to test the hypothesis that the treatment of the a) brain-dead organ donor with N-octanoyl dopamine will improve cardiac function in the donor and reduce ischemia/reperfusion injury after cardiac preservation and transplantation and b) transplant recipient before the onset of the reperfusion will improve graft cardiac function.