LIVER PRESERVATION FOR CLINICAL TRANSPLANTATION

肝移植(LTX)是各种肝脏的公认治疗方法。 疾病。然而，存在两个问题：初级无功能(PNF)和 肝脏短缺。PNF，由保存或再灌流损伤引起， 需要再次移植。这导致了肝脏的短缺。 PNF导致LTX和重要患者的巨额成本 不舒服。改善肝脏的保存将有助于 显著改善了LTX的结果。我们在这个项目中的目标是 改善肝脏保存，减少PNF，降低成本，降低成本 等待名单上的肝脏短缺和死亡，提供了一种方法 判断肝脏的生存能力，提高边缘肝脏的利用率 (缺血)。我们假设肝脏的显著改善 保存将需要持续的低温机器灌流(HMP)。 我们将证明优良品质的可行性，长期 HMP保存肝脏可达到以下五个特定目的：1) 优化肝脏灌流方法；2)优化灌流液 特别是肝脏，3)通过细胞保护来加强保存 以前被证明可以减少肝脏损伤的药物，4)发展出一种生存能力 基于肝脏低温代谢的分析，以及5)优化HMP 肝脏挽救边缘(缺血损伤的)肝脏。这些是如何 研究策略影响肝脏的质量和寿命 保存情况将通过大鼠原位肝脏的存活率来判断 移植模型(OLTx)和代谢损伤程度。使用 分离灌流肝(IPL)。微血管系统的完整性和 正弦波将通过电子显微镜进行评估。展示的战略 大鼠肝脏保存的显著增强将在#年得到证实 狗肝TX模型。产生的新信息将导致更多 全面了解肝脏保存/再灌注损伤， 开发最新的肝脏保存技术，提供措施 HMP期间的肝脏活性，并通过抢救来增加供体池 边缘肝。成功的HMP可能会对 临床LTX的结果并成为广大患者的首选技术 像我们这样的移植中心。

Liver transplantation (LTx) is accepted therapy for various liver diseases. However, there are two problems: primary nonfunction (PNF) and shortage of livers. PNF, caused by preservation or reperfusion injury, necessitates a retransplant. This contributes to the shortage of livers. PNF contributes to the enormous cost of LTx and significant patient discomfort. Improving preservation of the liver would contribute significantly to improved results in LTx. Our goals in this project are to improve liver preservation to reduce PNF, decrease cost, decrease shortage of livers and deaths on the waiting list, provide a method to judge viability of the liver, and increase utilization of marginal livers (ischemic). We hypothesize that significant improvements in liver preservation will require continuous hypothermic machine perfusion (HMP). We shall demonstrate the feasibility of excellent quality, long-term liver preservation by HMP accomplishing these five specific aims: 1) optimize the method of liver perfusion, 2) optimize the perfusate specifically for the liver, 3) enhance preservation with cytoprotective agents previously shown to decrease liver injury, 4) develop a viability assay based on liver hypothermic metabolism, and 5) optimize HMP of the liver to salvage marginal (ischemically injured) livers. How these research strategies affect the quality and longevity of liver preservation will be judged by survival in the orthotopic rat liver transplant model (OLTx) and the degree of metabolic injury.using the isolated perfused liver (IPL). Integrity of the microvascular system and sinusoids will be assessed by electron microscopy. Strategies that show significant enhancement of rat liver preservation will be confirmed in the dog liver Tx model. The new information generated will lead to a more comprehensive understanding of liver preservation/reperfusion injury, develop a new state-of-the-art for liver preservation, provide measures of liver viability during HMP, and increase the donor pool by salvaging marginal livers. Successful HMP could have a dramatic effect on the outcome of clinical LTx and become the technique of choice in large transplant centers such as ours.