Hormonal resuscitation and p38 MAP kinase inhibition to enhance quality of cadaveric donor organs for transplantation

从脑死亡的供者身上移植心脏、肺、肝、肾和胰腺等器官主要受到供体器官短缺的限制。现在人们认识到，由于脑死亡后器官的迅速恶化，多达25%(四分之一)的潜在可用的捐献器官在脑死亡后丢失。有证据表明，这种恶化是由于这些器官正常运作所必需的正常荷尔蒙的丧失。在这个项目中，我们将使用我们实验室建立的猪脑死亡模型来检验激素替代对用于移植的器官功能的影响。我们还将测试一种新药，目的是在器官摘除和移植之间保护供体器官。如果成功，这些治疗有可能显著增加器官移植的数量，并改善这些移植的接受者的结局。在澳大利亚和新西兰的情况下，捐赠器官数量增加25%，每年将导致大约220人接受这些挽救生命的手术。

The transplantation of organs such as the heart, lung, liver, kidney and pancreas from brain-dead donors is limited primarily by the shortage of donor organs. It is now recognised that as many as 25% (one in four) potentially usuable donor organs are lost after brain death due to the rapid deterioration that occurs in organs after brain death. There is evidence that this deterioration is due to loss of the normal hormones that are essential to the normal functioning of these organs. In this project, we will use a pig model of brain death that we have extablished in our laboratory to examine the effects of hormone replacement on the function of organs that are used for transplantation. We will also test a novel drug aimed at protecting donor organs during the period between removal of the organ and transplantation. If successful, these treatments have the potential to markedly increase the numbers of organ transplants and to improve the outcomes for recipients of these transplants. In the Australian and New Zealand setting, a 25% increase in the number of donor organs would results in approximately 220 more people per year receiving these life-saving operations.