DEMAND INDUCED ISCHEMIA IN A BLOOD PERFUSED LANGENDORFF

该提案的总体目标是描述需求诱导的特征 脑缺血在代谢、结构和功能方面的改变 兰登多夫浑身是血。临床上，可以观察到需求诱导 冠心病和劳力性心绞痛患者的日常生活和 可能存在于远离脑梗塞组织的患者 急性心肌梗死期间的多支血管疾病。需求诱导 缺血是在维持氧气的同时增加需氧量而产生的。 供应常数，是一种既往无特征性的病理生理模型 心肌缺血的症状。朗格多夫的血液是最近才出现的 开发了具有生理灌流的离体心制剂和 代谢率。需求诱导的缺血的特征将是 通过比较代谢、结构和功能 在血流减少的缺血和再灌注期间观察到的变化 常氧增加了工作。具体地说，氧气消耗的差异， 葡萄糖和棕榈酸的氧化，乳酸和丙酮酸的产生， 大鼠心肌高能磷酸、糖原、乳酸和丙酮酸含量 将对需求诱导和减少的血流缺血进行评估并与 氧供需失衡的严重程度。形态上的证据 按需诱导的缺血60分钟后的缺血损伤将 寻找并比较在减少血流缺血和脑缺血中获得的结果 常氧增功实验。因为氧化代谢是 需求诱导的缺血相对减少的血流缺血增加， 酰基钴和肉碱在组织中的蓄积可能有所不同 不同类型的缺血对血管紧张素转换酶的敏感性不同 棕榈酸灌流液浓度升高对心脏的不良影响 缺血左心功能。提出了一种特定的协议来 调查这些可能性。最后，绝对灌流的效果 将评估减少血流缺血期间的葡萄糖利用率 在缓冲液和血液灌流的心脏。这些项目的完成将 提供并初步描述了一种新的、与临床相关的模型 生理性离体心制剂中的心肌缺血。

The overall goal of this proposal is to characterize demand induced ischemia in terms of alterations in metabolism, structure and function in the blood perfused Langendorff. Clinically, demand induced is witnessed daily in patients with coronary artery disease and exertional angina and may exist in regions remote from infarcted tissue in patients with multivessel disease during an acute myocardial infarction. Demand induced ischemia is produced by increasing oxygen demand while maintaining oxygen supply constant and is a previoulsy uncharacterized pathophysiologic model of myocardial ischemia. The blood perfused Langedorff is a recently developed isolated heart preparation with physiologic perfusion and metabolic rates. Characterization of demand induced ischemia will be undertaken by comparing the metabolic, structural and functional alterations observed to those encountered during reduced flow ischemia and normoxic increased work. Specifically, differences in oxygen consumption, glucose and palmitate oxidation, lactate and pyruvate production, myocardial high energy phosphate, glycogen, lactate and pyruvate content in demand induced and reduced flow ischemia will be evaluated and related to the severity of oxygen supply-demand imbalance. Morphologic evidence of ischemia injury following 60 minutes of demand induced ischemia will be sought and compared to results obtained in reduced flow ischemia and normoxic increased work experiments. Because oxidative metabolism is increased in demand induced ischemia relative to reduced flow ischemia, tissue accumulation of acyl-Co and carnitine might be different in the two types of ischemia which could produce differing sensitivities to the deleterious effects of increased perfusate palmitate concentration on ischemia left ventricular performance. A specific protocol is proposed to investigate these possibilities. Finally, the effect of absolute perfusion rate on glucose utilization during reduced flow ischemia will be evaluated in buffer and blood perfused hearts. Completion of these projects will provide and initial characterization of a new, clinically relevant model of myocardial ischemia in a physiologic isolated heart preparation.