ENERGETICS & CATION MOVEMENTS IN POSTISCHEMIC HEART

能量学

• 批准号: 3361692
• 负责人: JOANNE S INGWALL
• 金额: $ 24.25万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-30 至 1994-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3361692
• 关键词: cations; electrochemistry; ferrets; heart circulation; heart contraction; heart metabolism; high energy compound; laboratory rat; membrane potentials; myocardial ischemia /hypoxia; nuclear magnetic resonance spectroscopy; sarcolemma; sodium potassium exchanging ATPase

Proposed mechanisms for decreased myocardial systolic function following ischemic injury include two interrelated processes: impaired energy production, utilization or transfer, and abnormalities of electromechanical coupling related to cation metabolism. Identifying the energetic requirements for maintaining normal transmembrane ion gradients during reperfusion following ischemic insult is an important and unsolved problem. By employing newly developed techniques using 31p, 23Na and 39K NMR spectroscopy, we are now in an unique position to define changes in energetics and transmembrane cation gradients, and their relation, during and following ischemic injury. By using cation NMR techniques developed in this laboratory, we can now define the transsarcolemmal proton, sodium and potassium gradients during and following ischemic injury. In this application, we propose four specific aims using NMR spectroscopy and imaging to define high-energy phosphate content and turnover and the transmembrane gradients of the cations, H+, NA+ K+ and Ca2+, while simultaneously monitoring cardiac performance in postischemic myocardium. 1) to define movements of Na+, K+,H+, and Ca2+ across the sarcolemma in the postischemic myocardium following mild (stunned), moderate and severe ischemia; 2) to construct a kinetic model describing these movements; 3) to relate these changes in cation transport to changes in high-energy phosphate content and turnover rates; and 40 to use 23Na chemical shift imaging in combination with a cationic shift reagent to track the movements of intra-and extracellular Na+ during and following regional ischemia in the isolated heart and the heart in situ.

术后心肌收缩功能下降的可能机制 缺血性损伤包括两个相互关联的过程：能量受损 生产、利用、转让及异常情况 与阳离子代谢有关的机电耦合。识别 维持正常跨膜离子梯度的能量需求 缺血再灌注损伤是一个重要且尚未解决的问题 有问题。通过使用使用31P、23Na和39K的新开发技术 核磁共振光谱学，我们现在处于一个独特的位置来定义 能量学和跨膜阳离子梯度及其关系 以及在缺血损伤后。通过使用开发的阳离子核磁共振技术 在这个实验室里，我们现在可以定义跨肌膜质子，钠 以及在缺血损伤期间和之后的钾梯度。在这 应用，我们提出了四个特定的目标，使用核磁共振波谱和 成像以定义高能磷酸盐含量和周转以及 阳离子、H+、Na+、K+和Ca~(2+)的跨膜梯度 同时监测缺血后心肌的心功能。 1)确定Na+、K+、H+和Ca~(2+)在肌膜上的运动 轻度(顿抑)、中度和重度缺血后心肌 2)建立描述这些运动的动力学模型；3) 将阳离子转运的这些变化与高能的变化联系起来 磷酸盐含量和周转率；40%使用23Na化学位移 结合阳离子移位试剂进行成像以追踪 大鼠局灶性脑缺血后细胞内和胞外Na+的运动 离体心和在位心脏的缺血。