REDUCTION OF INFARCT SIZE AFTER SURGICAL REPURFUSION

急性缺血和梗死心肌的再灌注 通过链激酶/溶栓，通过PTCA，通过急性冠状动脉 手术或所有这些方法的组合已经成为 越来越多地使用。 因此，术中心肌 保护缺血心肌，减少 冠状动脉闭塞再灌注后心肌损伤 仍然是最高优先事项。 根据我们的工作 从1981年开始，并继续通过RO 1赠款期间，我们 已经建立了更复杂的技术来评估当地的 急性冠状动脉闭塞后的整体心肌功能， 已经开始评估增加氧气输送的药物 缺血心肌或干扰 缺血和再灌注的影响。 在这段时间里，我们将继续努力， 在再灌注前准备缺血区域以及 治疗急性心肌梗塞的病理生理效应 缺血并发症。 我们将评估1）自由氧自由基 在急性和慢性缺血模型中，以及 体内保存的心脏，以更精确地定义 它们的作用，2）血栓素合成酶抑制剂， 急性和慢性模型，3）钙通道阻滞剂和4）药物 增加对缺血心肌的氧气输送， 氧合晶体心脏停搏液、血液心脏停搏液和 碳氟化合物 此外，我们还打算探索使用其他 保护剂，特别是氧合心脏停搏剂 应用于冠状动脉闭塞部位远端的化合物 在我们的模拟冠状动脉PTCA治疗的闭合胸部模型中， 闭塞 这些研究将对前- 医院，侵入性和手术治疗急性心肌梗死，领先 美国的死因通过减少 改善局部心肌功能 这些实验方法，早期和晚期死亡后， 心肌梗死应得到改善。

Reperfusion of the acutely ischemic and infarcted human myocardium by Streptokinase/thrombolysis, by PTCA, by acute coronary artery surgery or a combination of all these methods has become increasingly utilized. Therefore, intraoperative myocardial protection of the ischemic myocardium to reduce the magnitude of the myocardial injury after coronary occlusion and reperfusion continues to be of the highest priority. Based on our work beginning in 1981, and continuing through the RO1 grant period, we have established more sophisticated techniques to evaluate local and global myocardial function after acute coronary occlusion and have begun to evaluate agents to either increase delivery of oxygen to ischemic myocardium or to interfere with the pathophysiologic effects of ischemia and reperfusion. In this grant period we will continue to pursue the concept of preparation of the ischemic area prior to reperfusion as well as treatment of the pathophysiologic effects of acute myocardial ischemia concurrently. We will evaluate 1) free oxygen radicals in both the acute and chronic ischemia models as well as the ex vivo preserved heart to define more precisely the mechanisms of their action, 2) thromboxane synthetase inhibitors in both the acute and chronic model, 3) calcium channel blockers and 4) agents that increase oxygen delivery to the ischemic myocardium, oxygenated crystalloid cardioplegia, blood cardioplegia and fluocarbons. In addition we intend to explore the use of other protective agents, particularly the oxygenated cardioplegic compounds applied distal to the site of coronary artery occlusion in our closed chest model simulating PTCA treatment of coronary occlusion. These studies will impact positively on the pre- hospital, invasive and operative treatment of acute MI, the leading cause of death in America. By reducing the total amount of infarcted muscle and improving regional myocardial function by these experimental approaches, the early and late mortality after myocardial infarction should be improved.