NMR MEASUREMENT OF NA+ GRADIENT AND ENERGETICS--ISCHEMIA

这个计划的基本假设是， Na~+/K~+-ATPase维持缺血心肌标志物的Na~+梯度 监管失灵的开始。因此，此应用程序的前提是 具体如下：第一，脑缺血的主要结果是 心肌是高能的磷酸盐，HEP，耗竭和，改变在 肌膜阳离子梯度；第二，这些过程是 相互依赖；第三，维持正常心肌细胞内 缺血时钠离子浓度[Na+]i取决于自由能 三磷酸腺苷的水解度；三角洲/GATP。首先，我们将建立时态 HEP和Na+梯度对缺血再灌流的反应这个 总体目标是定义HEP变化之间的关系 以及心肌缺血时钠离子梯度的变化。 在完整的心脏中再灌流。为了实现这些目标，一个模型 完整心脏的缺血和再灌流。要实现这些目标 目的建立完整猪心脏缺血再灌注模型。 受雇的。猪心中缺乏预先形成的侧支血管 能够比可能的程度更完全地控制缺血的程度 更常用的犬类模型。正常人的心脏会这样做 没有经络。因此，猪心模型可能与 对某些人类缺血综合征的研究。采用核磁共振波谱技术 连续测定磷酸化代谢物和Na+梯度 在整个对照、缺血和再灌注过程中。功能参数和 流动将被同时监测并与代谢物相关联 测量。急性心肌梗死的治疗近些年来 通过使用溶栓剂迅速进化，导致 缺血区再灌流。在临床情况下，如 再灌注量有限，但不能防止坏死。身份识别 代谢事件的时间和关系导致 缺血性心脏的调节失效是合理设计的关键 新的治疗策略。因此，它可能会产生广泛的影响 在心脏护理方面。

The fundamental hypothesis of this program is that the failure of the Na+/K+ ATPase to maintain the Na+ gradient in the ischemic myocardium marks the onset of regulatory failure. Thus, the premises of this application are as follows: first, that the primary result of ischemia in the myocardium is high-energy phosphate, HEP, depletion and, alterations in the sarcolemmal cation gradients; second, that these processes are interdependent; third, that maintenance of normal myocardial intracellular sodium concentration, [Na+]i, during ischemia depends upon the free energy of ATP hydrolysis; delta/GATP. First, we will establish the temporal responses of the HEP and the Na+ gradient to ischemia and reperfusion. The overall objective is to define the relationship between changes in the HEP and the changes in the Na+ gradient during myocardial ischemia and reperfusion in the intact heart. To accomplish these objectives a model of ischemia and reperfusion in the intact heart. To accomplish these objectives a model of ischemia and reperfusion in the intact pig heart is employed. The lack of pre-formed collateral vessels in the pig heart enables more complete control of the degree of ischemia than is possible with the more commonly employed canine model. The normal human heart does not have collaterals. Thus, the pig heart model may be more relevant to the study of some human ischemic syndromes. NMR spectroscopy is employed to serially measure the phosphorylated metabolites and the Na+ gradient throughout control, ischemia, and reperfusion. Functional parameters and flows will be simultaneously monitored and correlated with the metabolite measurements. The treatment of acute myocardial infarction has recently evolved rapidly through the use of thrombolytic agents, resulting in reperfusion of the ischemic region. Under clinical circumstances such reperfusion limits but, does not prevent necrosis. Identification of the timing and of the relationship of the metabolic events leading to regulatory failure in the ischemic heart is crucial to the rational design of new therapeutic strategies. Thus, it has a potentially broad impact upon cardiac care.