NMR MEASUREMENT OF NA+ GRADIENT AND ENERGETICS--ISCHEMIA

NA 梯度和能量的 NMR 测量——缺血

• 批准号: 3473430
• 负责人: James Alvin Balschi
• 金额: $ 9.77万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-12 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473430
• 关键词: disease /disorder model; divalent cations; fibrinolytic agents; heart circulation; heart disorder diagnosis; heart failure; heart pharmacology; high energy compound; intracardiac pressure; lidocaine; membrane transport proteins; miniature swine; myocardial ischemia /hypoxia; nuclear magnetic resonance spectroscopy; potassium; reperfusion; sarcolemma; sodium; sodium potassium exchanging ATPase

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.

该计划的基本假设是， Na+/K+ ATP酶维持缺血心肌Na+梯度的标志 监管失败的开始。 因此，本申请的前提 主要原因如下：首先， 心肌是高能磷酸盐，HEP，消耗和，在改变 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 缺血期间的钠浓度[Na+]i取决于自由能 ATP水解; delta/GATP。 首先，我们将建立时间 HEP和Na+梯度对缺血和再灌注的反应。 的 总体目标是确定HEP变化之间的关系 以及心肌缺血时Na+梯度的变化， 在完整的心脏再灌注。 为了实现这些目标， 在完整心脏中的缺血和再灌注。 完成这些 目的建立完整猪心缺血再灌注模型， 就业。 猪心缺乏预先形成的侧支血管 使得能够比可能的更完全地控制缺血程度 与更常用的犬模型进行比较。 正常人的心脏 没有抵押品。 因此，猪心脏模型可能更相关于 对某些人类缺血综合征的研究。 采用NMR光谱法 连续测量磷酸化代谢物和Na+梯度 在整个对照、缺血和再灌注期间。 功能参数和 将同时监测流量并与代谢物相关联 测量. 急性心肌梗死的治疗方法 通过使用血栓溶解剂迅速发展， 缺血区域的再灌注。 在临床情况下， 再灌注限制，但不能防止坏死。 识别 时间和代谢事件的关系，导致 缺血心脏的调节失败对于合理设计至关重要 新的治疗策略。 因此，它具有潜在的广泛影响， 心脏护理。