OPTIMIZING CORONARY FLOW TO REDUCE MYOCARDIAL STUNNING

优化冠状动脉血流以减少心肌顿抑

• 批准号: 6204204
• 负责人: ALICE HSI HUANG
• 金额: $ 9.59万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6204204
• 关键词: acid base balance; calcium ion; free radical oxygen; heart circulation; heart contraction; heart function; ion transport; laboratory rat; myocardial ischemia /hypoxia; myocardium; myocardium disorder; oxygen consumption; reperfusion; vascular smooth muscle

The myocardium becomes ischemic and is reperfused under pathological conditions, such as coronary vasospasm, and also in the course of treatments such as coronary angioplasty and various cardiothoracic surgical procedures. After such a period of ischemia, the contractile function of the myocardium may be impaired for hours or days, although there is no evidence of infarction, and the myocardium does eventually recover normal function. The pilot research project proposed here is designed to test the hypothesis that this myocardial stunning is mediated, at least in part, by delivery of excess blood flow to the myocardium during reperfusion, due to impairment of coronary vascular smooth muscle function. Experiments will be performed with Langendorff perfused isolated rat hearts, under both conditions of controlled flow, and conditions of controlled perfusion pressure. The specific aims are (1) to define a protocol for producing consistent and severe myocardial stunning, (2) to identify reperfusion protocols that reduce stunning, (3) to test possible mechanisms by which excess blood flow mediates myocardial stunning, and (4) to test possible coronary vascular mechanisms responsible for excess delivery of flow to the myocardium during reperfusion. Mechanisms that will be considered, for both the changes in myocardial functions and the changes in coronary vascular function, include (1) generation of harmful quantities of oxygen-derived free radicals, 92) acid-based derangements secondary to inappropriate accumulation or washout of carbon dioxide, and (3) impairment of Ca/++-transport by the myocytes or vascular smooth muscle cells, secondary to changes in electrochemical gradients. An understanding of the mechanisms by which excess is delivered to the myocardium, and the mechanisms by which excess flow promoters myocardial stunning is fundamental to the development of clinically applicable procedures for preventing or reversing myocardial stunning, as well as to basic understanding of coronary and myocardial function.

心肌缺血并在病理条件下再灌注 条件，如冠状动脉血管痉挛，也在过程中， 冠状动脉血管成形术和各种心胸外科手术等治疗 外科手术经过这样一段时间的缺血， 心肌功能可能受损数小时或数天，尽管 没有梗塞的证据，心肌最终 恢复正常功能。这里提出的试点研究项目是 旨在检验这种心肌顿抑是介导的假设， 至少部分地通过向心肌输送过量的血流 在再灌注期间，由于冠状动脉血管平滑肌受损， 功能实验将使用Langendoff灌注隔离进行 大鼠心脏，在两种条件下的控制流，和条件下， 控制灌注压。具体目标是：（1）确定一个 产生一致和严重心肌顿抑的方案，（2）至 确定减少昏厥的再灌注方案，（3）测试可能的 过量血流介导心肌顿抑的机制，以及 (4)以测试可能的冠状血管机制， 在再灌注期间将血流输送到心肌。机制 将考虑心肌功能的变化和 冠状动脉血管功能的变化，包括（1）有害的生成 氧自由基的数量，92）酸基紊乱 其次是二氧化碳的不适当积累或清除，以及 (3)心肌细胞或血管平滑肌Ca/++转运障碍 肌肉细胞，继发于电化学梯度的变化。一个 了解过剩输送到 心肌，以及过度血流促进心肌 致晕是临床应用的基础 预防或逆转心肌顿抑的方法，以及 对冠状动脉和心肌功能有基本了解。