REPEATED BRIEF CORONARY OCCLUSIONS: EFFECT ON FUNCTION

人的短暂性心肌缺血，如果足够短暂，通常是 被认为是一种可逆的侮辱，恢复得很快很彻底。 然而，在动物模型中短暂的冠状动脉闭塞表明 心肌收缩的局部异常可以延长，很好 超过缺血期。初步调查显示 证明了反复短暂的冠状动脉闭塞会导致 进行性和显著的节段性心功能不全 永久性细胞损伤的证据。由于反复出现的短暂发作 已知缺血发生在人身上，可能是频繁的，也可能没有 症状，重要的是要定义这些事件的后果 心肌功能。这项建议将检查异常机械 犬反复短暂冠脉病变慢性模型的功能研究 闭塞。局部功能将用植入的超声进行测量 时间传递测量仪；心肌血流量将从 注射放射性标记的微球；以及细胞 损伤将通过组织化学染色和组织学来确定。这个 机械损伤的程度和持续时间将作为函数进行检查 缺血发作的次数、频率和持续时间。一次尝试 将通过以下方式来确定潜在的病理生理机制 腺嘌呤核苷酸、线粒体的定量测量 呼吸作用和肌浆网钙摄取。最后， 逆转或预防机械功能障碍的治疗策略 将会被检查。这些研究将定义 反复出现短暂的缺血发作，可能会导致对 缺血性心肌病的发病机制及治疗。

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.