PROTECTION FROM CARDIAC REPERFUSION INJURY BY ETHANOL

申请人摘要：适度使用乙醇与保护有关 对抗致命的冠心病 然而，除了减少 冠状动脉事件的发生率，事件后恢复的改善可能是 在乙醇预防冠状动脉疾病致死性结局中的重要性 疾病 减轻缺血后再灌注损伤是一种机制， 心肌恢复，从而存活率，可以改善后， 冠心病事件 初步研究表明，适度使用乙醇会减弱 腺苷受体激活对豚鼠再灌注损伤的影响 心中 将针对问题1 -5对假设I和II进行检验： I.适度使用乙醇可保护心肌缺血后 再灌注 损伤 1. 适度使用乙醇是否能改善功能和代谢 恢复 在再灌注过程中？ 2. 缺血再灌注后，适度使用乙醇 减少灌注心脏中心肌细胞坏死的量， 体内梗死面积？ 3. 适度使用乙醇是否可以防止在 缺血再灌注后 二. 适量乙醇对再灌注损伤的保护作用 损伤 是腺苷受体介导的蛋白激酶C 易位 4. 乙醇的保护作用是否被腺苷A1，A2， 和/或A3受体拮抗剂？ 5. 乙醇引起的心肌细胞中δ和β-PKC转位 暴露的心脏和对照的心脏 离体豚鼠心脏（喂食10%乙醇6周）将经历 缺血再灌注。 能源消耗和恢复将通过 31 P-MRS;肌酸激酶释放引起的肌细胞坏死; indo-1荧光和PKC同工酶易位 定位和蛋白质印迹分析。 在体内，梗死面积将是 在左冠状动脉闭塞-再灌注后测量。 本研究的最终目标是：1）建立起一种机制， 适度饮酒与心脏病之间的正相关性 2）帮助制定治疗干预措施， 在有致命性冠状动脉事件风险的患者中模拟这种效应， 选择性或紧急再灌注。

APPLICANT'S ABSTRACT: Moderate ethanol use is associated with protection against fatal coronary events. However, in addition to a decreased incidence of coronary events, improved recovery following an event may be important in ethanol's prevention of fatal outcomes due to coronary artery disease. Attenuation of post-ischemic reperfusion injury is a mechanism by which myocardial recovery, and thereby survival, may be improved following a coronary event. Pilot studies suggest that moderate ethanol use attenuates reperfusion injury through activation of adenosine receptors in guinea pig hearts. Hypotheses I and II will be tested addressing questions #1-5: I. Moderate ethanol use protects against myocardial post-ischemic reperfusion injury. 1. Does moderate ethanol use improve functional and metabolic recovery during reperfusion? 2. Following post-ischemic reperfusion, does moderate ethanol use decrease the amount of myocyte necrosis in perfused hearts and infarct size in vivo? 3. Does moderate ethanol use protect against Ca2+ overload during post-ischemic reperfusion? II. The protective effect of moderate ethanol use against reperfusion injury is the result of adenosine receptor mediated protein kinase C translocation. 4. Is ethanol's protective effect abolished by adenosine A1, A2, and/or A3 receptor antagonists? 5. Are delta and epsilon PKC translocated in myocytes from ethanol exposed hearts versus controls? Isolated guinea pig hearts (fed 10% ethanol for 6 weeks) will undergo ischemia - reperfusion. Energy depletion and recovery will be assessed with 31P-MRS; myocyte necrosis by creatine kinase release; cytosolic CA2+ by indo-1 fluorescence; and PKC isozyme translocation by immunofluorescence localization and western blot analysis. In vivo, infarct size will be measured after occlusion-reperfusion of the left coronary artery. The ultimate goals of this research are 1) to establish the mechanisms underlying the positive association between moderate alcohol use and cardiac health and 2) aid in the development of therapeutic interventions which mimic this effect in patients at risk for fatal coronary events who require elective or emergent reperfusion.