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

心脏移植成为治疗终末期心脏病最有效的方法。供体短缺的恶化和等待移植的患者数量的增加限制了这一过程。脑死亡后的供者是目前唯一可靠的心脏移植来源。然而，脑死亡的供者存在血流动力学不稳定和心功能障碍，这也可能影响心脏移植后的移植物功能。预适应是改善供体器官功能和保护同种异体移植物免受低温保存/再灌注损伤的潜在策略之一。已有研究表明，对潜在器官供者进行小剂量多巴胺治疗可改善心脏和肾脏移植后早期移植肾功能和存活率。由于多巴胺的可能副作用(心动过速、高血压危象)可能阻止其常规使用，一种新的多巴胺类似物N-辛酰基多巴胺已被开发出来，它对多巴胺受体没有任何影响，从而没有任何血流动力学作用。本提案的主要目的是验证这样一种假设：a)脑死亡器官供者在心脏保存和移植后用N-辛酰多巴胺治疗将改善供者的心功能，减少缺血/再灌注损伤；b)移植受体在再灌流开始之前将改善移植物心脏功能。

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.