ORGAN PRESERVATION FOR TRANSPLANTATION

肾移植手术是一种公认的治疗方式 终末期肾病患者和超过8,000例手术 每年在美国演出。缺乏供体器官，排斥反应，以及 保存/再灌注损伤是体外循环中需要克服的主要障碍。 肾移植。保存再灌注损伤导致延迟 术后需要血液透析的移植物功能(DGF)增加 程序的额外成本，并导致减少长期 肾脏存活时间(5年至10年)。在我们之前的一段时间 支持我们开发了一种新的保存方案(一种用于冷藏 一个用于机器灌流)用于肾脏和其他器官。这些 解决方案显著改善了肾脏的质量和持续时间(和 其他器官)保存。我们发现了一些问题， 肾脏保存包括微血管损伤和肾脏 与钙和可能的磷脂(花生四烯酸)有关的肾小管损伤 酸)代谢。 我们在这项提议中的基本假设是微血管损伤 可能是再灌流后肾损伤的主要原因。我们的整体 目标是了解细胞和生化机制 对肾脏的保存/再灌流损伤及进一步发展 有效的保存方法。 我们的具体目标是： L)了解保存下来的老年人微血管系统的变化 肾脏离体血和红细胞模型的建立 兔肾； 2)了解磷脂代谢之间的关系 (水解和反应)、二十烷类化合物的产生和微血管 保存或再灌流过程中肾小管的变化； 3)了解血管内皮细胞和肾小管上皮细胞如何受到损伤 体外血管内皮细胞低温保存和再灌流 肾小管细胞； 4)研究不同药剂和药物对中药质量的影响 保存与建议有关的兔器官和分离细胞 损伤机制； 5)利用临床相关的犬自体肾移植模型 测试新的和改进的肾脏保存方法 具体目标1-4。 这些研究将为理解这些问题提供新的有用信息 肾脏移植物功能延迟的发病机制。新的 产生的信息将导致更好的肾脏保存，减少 成本和更好的人肾移植长期存活率 移植疗法。

Kidney transplantation surgery is an accepted form of therapy for patients with end stage renal disease, and over 8,000 surgeries are performed each year in the USA. Lack of donor organs, rejection, and preservation/reperfusion injury are the main obstacles to overcome in kidney transplantation. Preservation reperfusion injury leads to delayed graft function (DGF) requiring postoperative hemodialysis which adds additional cost to the procedure and results in reduced long-term survival of kidneys (5 to 10 years). During our previous period of support we developed a new preservation solution (one for cold storage and one for machine perfusion) for the kidney and other organs. These solutions improved dramatically the quality and duration of kidney (and other organ) preservation. We identified some of the problems with kidney preservation including microvascular injury as well as renal tubular injury related to calcium and possibly phospholipid (arachidonic acid) metabolism. Our underlying hypothesis in this proposal is that microvascular injury may be a primary cause of renal injury upon reperfusion. Our overall goal is to understand the cellular and biochemical mechanisms underlying preservation/reperfusion injury to the kidney and to develop more effective preservation methods. Our specific aims are: l) to understand changes in the microvascular system of the preserved kidney using blood and erythrocyte models of the isolated perfused rabbit kidney; 2) to understand the relationship between phospholipid metabolism (hydrolysis and reacylation) and eicosanoid production and microvascular and tubular changes during preservation or reperfusion; 3) to understand how endothelial cells and tubular cells are injured by hypothermic preservation and reperfusion using isolated endothelial and tubular cells; 4) to study how various agents and drugs affect the quality of preservation of rabbit organs and isolated cells as related to proposed mechanisms of injury; 5) to use the clinically relevant dog kidney autotransplant model to test new and improved methods of kidney preservation derived from specific aims 1-4. These studies will provide new and useful information for understanding the pathogenesis of delayed graft function in the kidney. The new information generated will lead to better renal preservation, reduced cost, and better long-term graft survival in human kidney transplantation therapy.