ENERGETICS & CATION MOVEMENTS IN POSTISCHEMIC HEART

能量学

• 批准号: 3361694
• 负责人: JOANNE S INGWALL
• 金额: $ 27.01万
• 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/3361694
• 关键词: adenosinetriphosphatase; calcium; cations; electrochemistry; ferrets; heart circulation; heart contraction; heart metabolism; high energy compound; hydrogen; ion transport; laboratory rat; membrane potentials; membrane transport proteins; myocardial ischemia /hypoxia; nuclear magnetic resonance spectroscopy; potassium; sarcolemma; sodium

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.

心肌收缩功能降低的机制 缺血性损伤包括两个相互关联过程：能量受损 生产、利用或转让，以及 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 在缺血损伤后的再灌注期间， 问题.采用新开发的31 p、23 Na和39 K技术， 核磁共振光谱，我们现在处于一个独特的位置，以定义的变化， 能量学和跨膜阳离子梯度及其关系， 和缺血性损伤后。通过使用开发的阳离子NMR技术， 在这个实验室里，我们现在可以定义跨肌膜质子， 以及缺血性损伤期间和之后的钾梯度。在这 应用，我们提出了四个具体的目标，使用核磁共振光谱， 成像以确定高能磷酸盐含量和周转率， 阳离子H+、NA+、K+和Ca 2+的跨膜梯度，而 同时监测缺血后心肌中的心脏性能。 1)为了确定Na+、K+、H+和Ca 2+穿过肌膜的运动， 轻度（顿抑）、中度和重度缺血后心肌 缺血; 2）构建描述这些运动的动力学模型; 3） 将这些阳离子运输的变化与高能 磷酸盐含量和周转率;和40使用23 Na化学位移 成像与阳离子位移试剂组合以追踪 在区域性脑缺血期间和之后，细胞内和细胞外Na+的运动 在离体心脏和原位心脏中的缺血。