CARDIAC PRESERVATION PRIOR TO TRANSPLANTATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 成功的心脏移植取决于在获取和运输过程中充分保护供者心脏的能力。到目前为止，这是通过将冷保存溶液注入心脏并将心脏保存在冰柜中(静态保存)来实现的。这种方法有局限性，并导致了在运输过程中向供者心脏提供持续的含氧溶液(机器灌流保存)的技术的发展。这一新策略可能允许心肌中持续的氧化代谢，从而支持必要的细胞过程。然而，现有的保存液是为静态保存而设计的，不能很好地利用机器灌流提供的条件。该项目将检查在机器灌流保存期间和之后的心肌代谢，以确定保存液中最大限度地提高氧化代谢的底物条件。更多的实验将检验这一概念，即在储存过程中增加新陈代谢会在移植后产生更好的功能结果。 这项研究项目的具体目标是： 在心脏移植机器灌流保存的小动物模型中，验证不同外源性底物影响心肌氧化代谢程度的假设。 目的：确定在机器灌流保存过程中，使氧化代谢最大化的灌注液中的最佳底物组成和底物浓度。 为了在一个流量和心脏大小不同的大型动物(犬)模型中测试改变灌注液底物成分会对氧化代谢产生类似影响的假设。 目的：在一个大型动物模型中，测试在机器灌流保存期间外源底物氧化代谢速率增加对移植后心功能以及因坏死和凋亡造成的细胞损伤的影响。 来自这些研究的信息可能使我们能够开发改进的灌注液，用于机器灌流保存，从而在心脏移植中获得更好的结果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Successful cardiac transplantation depends on the ability to adequately protect the donor heart during procurement and transport. To date this has been accomplished by infusing a cold preservation solution into the heart and storing the heart in an ice chest (static preservation). This method has limitations and has led to the development of techniques that provide a continuous flow of oxygenated solution to the donor heart during transport (machine perfusion preservation). This new strategy may allow ongoing oxidative metabolism in the myocardium which can support essential cellular processes. However, existing preservation solutions are designed for static preservation and are not well suited to take advantage of the conditions provided by machine perfusion. This project will examine myocardial metabolism during and after machine perfusion preservation to identify substrate conditions in the preservation solution that maximize oxidative metabolism. Additional experiments will test the concept that increased metabolism during storage leads to superior functional results after transplantation. The specific aims of this research project are: To test the hypothesis that different exogenous substrates affect the degree of myocardial oxidative metabolism in a small animal model of machine perfusion preservation for heart transplantation. To determine the optimal substrate composition and substrate concentration in a perfusion solution to maximize oxidative metabolism during machine perfusion preservation. To test the hypothesis that altering perfusion solution substrate composition leads to similar effects on oxidative metabolism in a large animal (canine) model where flow rates and heart size are different. To test the effect of increased rates of oxidative metabolism of exogenous substrates during machine perfusion preservation on post-transplant ventricular function and cellular damage from necrosis and apoptosis in a large animal model. Information from these studies may enable us to develop improved perfusion solutions for use with machine perfusion preservation, leading to superior results in cardiac transplantation.