REPEATED BRIEF CORONARY OCCLUSIONS: EFFECT ON FUNCTION

人的短暂心肌缺血，如果时间足够短， 被认为是一种可逆的损伤，可以迅速而完全地恢复。 然而，动物模型中的短暂冠状动脉闭塞表明， 心肌收缩的局部异常可以延长， 超过缺血期。 初步调查显示， 表明反复短暂的冠状动脉闭塞可以产生 进行性和显著的局部心室功能障碍， 永久性细胞损伤的证据。 由于反复发作的 已知局部缺血发生在人体中，且可能是频繁且没有 症状，重要的是要确定这些事件的后果， 心肌功能 这项建议将检查异常的机械 在反复短暂冠状动脉粥样硬化后的慢性犬模型中的功能 闭塞。 将使用植入式超声波测量局部功能 时间传输计;心肌血流量将从 注射放射性标记的微球;和细胞的证据 损伤将由组织化学染色和组织学确定。 的 机械损伤的程度和持续时间将作为一个函数进行检查 缺血发作的次数、频率和持续时间。 试图 将确定潜在的病理生理机制， 腺嘌呤核苷酸的定量测量，线粒体 呼吸和肌浆网钙摄取。 最后， 逆转或预防机械功能障碍的治疗策略 将被审查。 这些研究将确定的功能意义 反复短暂的缺血发作，并可能导致新的见解， 缺血性心肌病的机制和治疗。

Transient myocardial ischemia in man, if sufficiently brief, is generally regarded as a reversible insult from which recovery is rapid and complete. Brief coronary artery occlusion in animal models, however, has shown that regional abnormalities of myocardial contraction can be prolonged, well beyond the period of ischemia. A preliminary investigation has demonstrated that repeated brief coronary occlusions can produce progressive and significant regional ventricular dysfunction without evidence of permanent cellular injury. Since recurrent brief episodes of ischemia are known to occur in man and may be frequent and without symptoms, it is important to define the consequences of these episodes on myocardial function. This proposal will examine abnormal mechanical function in a chronic dog model following repeated brief coronary occlusions. Regional function will be measured with implanted ultrasonic time transit gauges; myocardial blood flow will be quantitated from injections of radioactively labeled microspheres; and evidence of cellular damage will be determined from histochemical stains and histology. The degree and duration of mechanical impairment will be examined as a function of the number, frequency, and duration of ischemic episodes. An attempt will be made to determine the underlying pathophysiologic mechanism by quantitative measurements of adenine neucleotides, mitochondrial respiration, and sarcoplasmic reticulum calcium uptake. Finally, therapeutic strategies to reverse or prevent the mechanical dysfunction will be examined. These studies will define the functional significance of recurrent brief episodes of ischemia and may lead to new insight into the mechanism and therapy of ischemic cardiomyopathy.