DEMAND INDUCED ISCHEMIA IN A BLOOD PERFUSED LANGENDORFF

需求引起血液灌注兰根多夫缺血

• 批准号: 3354893
• 负责人: ROBERT C MARSHALL
• 金额: $ 6.69万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3354893
• 关键词: angina pectoris; coronary disorder; enzyme substrate; glucose metabolism; heart circulation; heart function; heart metabolism; high energy compound; isolation perfusion; myocardial infarction; myocardial ischemia /hypoxia; oxidation; oxygen consumption; phosphates

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.

本提案的总体目标是描述 缺血在代谢，结构和功能方面的改变， 血液灌满了兰根多夫 在临床上，需求诱导是见证 每日在冠状动脉疾病和劳力性心绞痛患者中， 可能存在于患者远离梗死组织的区域， 急性心肌梗死期间的多支血管疾病。 需求诱导 局部缺血是通过在维持氧气的同时增加氧气需求而产生的 供应常数，是一个先前未表征的病理生理模型 心肌缺血 Langedorff灌注的血液是最近 开发了具有生理灌注的离体心脏制备， 代谢率 需求诱导的缺血的表征将是 通过比较代谢，结构和功能 在血流减少缺血期间观察到的变化， 常氧增加功。 具体来说，氧气消耗的差异， 葡萄糖和棕榈酸氧化，乳酸和丙酮酸产生， 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价，并与 氧气供需失衡的严重程度。 的形态学证据 在60分钟的需求诱导的局部缺血之后的局部缺血损伤将 寻求并与减少血流缺血和 常氧增加工作实验。 因为氧化代谢是 相对于减少的血流缺血， 两种组织中酰基-Co和肉毒碱的积累可能不同 不同类型的缺血可能产生不同的敏感性， 增加灌注液棕榈酸酯浓度的有害影响 缺血性左心室功能。 提出了一个具体的协议， 调查这些可能性。 最后，绝对灌注的效果 将评价血流减少缺血期间葡萄糖利用率 在缓冲液和血液灌注的心脏中。 这些项目的完成将 提供并初步表征一种新的临床相关模型， 生理性离体心脏制备中的心肌缺血。