ALTERATIONS OF METABOLISM IN ISCHEMIC MYOCARDIUM

这些建议的目的是确定新陈代谢的限度 缺血心肌的适应性及对几种干预措施的评价 以提高能量生产和/或机械功能。我们观察到 以前认为心肌缺血的损害不仅仅是由于丢失 在氧气输送中，还会受到几种积聚的抑制 代谢物。尽管如此，修改或规避 这些产物可能会受到影响，以刺激残余的氧化磷酸化。 对工作猪心的研究计划继续这些研究。 重点将具体放在确定底物的影响上。 增强，记录旨在钝化效果的制剂的影响 脂肪酸过量，并进一步详细说明冠状动脉清洗的影响。 在提供以下方面可能具有特定优势的替代基板 乙酰辅酶A含量增加的线粒体，将在 即将到来的资助年度包括：乙酸盐、β-羟基丁酸酯和丙酮酸 二氯乙酸酯。用于改善脂肪酸过量的特定试剂 将是肉碱的各种异构体(L、D和DL)。实验将是 以评估和确定地震的大小和分布 肉碱的细胞内掺入及其异构体的影响 立体特异性，以及它们对修饰的潜在影响 改善缺血组织的能量产生。评估影响的研究 冠状动脉冲刷对保持新陈代谢和机械功能的作用 有计划的。研究将确定脑缺血是否会改变血管 再分配和含氧量。希望对这一问题的批评 通过这几种干预措施，心脏代谢和能量产生将 提供对未来可能的治疗方案的见解，以保护缺血 心肌。

The objects of these proposals are to establish the limits of metabolic adaptation in ischemic myocardium and to evaluate several interventions designed to improve energy production and/or mechanical function. We have observed previously that the damages of myocardial ischemia result not only from the loss in oxygen delivery, but also from an accumulation of several inhibitory metabolites. Nevertheless, manipulations which either modify or circumvent these products can be affected to stimulate residual oxidative phosphorylation. Studies in working swine hearts are planned to continue these investigations. Emphasis will be specifically directed at determining the effects of substrate enhancement, documenting the influence of agents designed to blunt the effects of fatty acid excess, and further detailing the impact of coronary washout. Alternate substrates which may have specific advantages in providing mitochondria with increased amount of acetyl-CoA and which will be evaluated in the coming grant year include: acetate, beta-hydroxybutyrate and pyruvate with dichloro acetate. Specific agents to be used in modifying fatty acid excess will be the various isomers (L, D and DL) of carnitine. Experiments will be formed to evaluate and determine the magnitude and distribution of the intracellular incorporation of carnitine, the effects of their isomeric stereospecificity, and their potential impact on modifying and hopefully improving energy production in ischemic tissue. Studies to evaluate the impact of coronary washout on preserving metabolic and mechanical functions are also planned. Studies will determine whether washout in ischemia alters vascular redistribution and oxygen content. It is hoped that a critical evaluation of cardiac metabolism and energy production with these several interventions will provide insights to possible future therapeutic options for protecting ischemic myocardium.