PROTECTING KIDNEYS FROM ISCHEMIC INJURY

目前，人类急性肾功能衰竭的主要原因是缺血性损害。 到了肾脏。在拟议的研究中，我们将评估和开发新的 保护性解决方案、药物和技术具有潜在的 显著减少或消除相关的急性肾功能衰竭 伴有冷热肾缺血。在一定程度上是基于 在我们先前修订的提案中概述，我们最近制定了一个 可完全预防急性肾功能衰竭的原位冲洗液 肾功能衰竭与肾脏热缺血一小时有关。在 建议的研究，我们将进一步测试这种热冲洗的潜力 解决方案，并尝试通过使用其他潜在的 更有效的渗透剂和药物。试点调查已经完成 建议简单地静脉注射某些药物或 渗透剂也能有效减少缺血后急性肾功能衰竭。 比目前可用的其他前处理方法更好。因此，我们将 单独和特定组合测试这些化合物，以研究它们的 减少热缺血对肾脏造成的肾损害的能力。 上述药物和/或渗透剂中最有效的也将 与ATP-MgCl2结合使用，这是一种将加速 肾细胞从缺血损伤中的恢复。先导移植 研究，广泛的形态研究，以及我们温泉的成功 所有的冲洗溶液都表明我们最近开发的冷冲洗和 储藏PBSucose溶液可能优于其他冷藏 目前用于保存肾脏的解决方案 移植。因此，在拟议的研究中，我们概述了 肾移植后肾功能评价的研究 这个新的解决方案。此外，我们似乎也有可能 能够通过使用(1)进一步改进此冷藏解决方案 更有效的渗透剂，(2)也能防止细胞肿胀的药物， (3)添加三磷酸腺苷-氯化镁可能会改善心脏功能。 冷和热缺血损伤的影响。所有上述内容 建议的技术、解决方案和要测试的化合物由 先前发表的调查和试点研究。总的来说，人们相信 这些研究将导致新的和非常有效的开发 减少与热或冷相关的急性肾功能衰竭的方法 缺血症。

Currently the major cause of acute renal failure in man is ischemic insult to the kidneys. In the proposed studies we will evaluate and develop new protective solutions, drugs, and techniques which have the potential of significantly reducing or eliminating the acute renal failure associated with warm or cold renal ischemia. Based in part on principles which were outlined in our previously revised proposal, we have recently developed an in situ flushing solution which will completely prevent the acute renal failure associated with one hour of warm ischemia to the kidneys. In the proposed studies, we will further test the potential of this warm flushing solution and attempt to improve it through the use of other potentially more effective osmotic agents and drugs. Pilot investigations have suggested that simple intravenous administration of certain drugs or osmotic agents can also effectively reduce postischemic acute renal failure better than other currently available pretreatments. We will therefore test these compounds both alone and in specific combinations to study their ability to reduce renal damage resulting from warm ischemia to kidneys. The most effective of the foregoing drugs and/or osmotic agents will also be used in combination with ATP-MgCl2, a compound which will accelerate recovery of renal cells from ischemic injury. Pilot transplantation studies, extensive morphological studies, and the success of our warm flushing solution all suggest that our recently developed cold flushing and storage PBSucrose solutions are probably superior to other cold storage solutions which are currently used to preserve kidneys prior to their transplantation. In the proposed studies, we have therefore outlined studies to evaluate the post-transplantation function of kidneys stored in this new solution. In addition, it appears not unlikely that we may be able to further improve this cold storage solution through the use of (1) more effective osmotic agents, (2) drugs which also prevent cell swelling, and (3) the addition of ATP-MgCl2 which may be able to ameliorate the effects of cold as well as warm ischemic damage. All the foregoing proposed techniques, solutions, and compounds to be tested are supported by prior published investigations and pilot studies. Together, it is believed that these studies will result in the development of new and very effective ways to reduce the acute renal failure associated with either warm or cold iscemia.