SUBSTRATE MODIFICATION FOR MYOCARDIAL PROTECTION

目前研究的目标之一是开发和测试 用于心脏停搏液的底物增强剂的替代形式， 作为心脏直视手术心肌保护策略的补充 手术 我们对二氯醋酸盐（DCA）的影响进行了研究， 在前面的研究亮点部分已经介绍过了。 我们有 还启动了丙酸盐的研究， 细胞能量学，在文献中得到支持，但没有 被测试为心脏停搏液的添加剂。 我们的初步研究 已经进行了调查这种干预的背景下， 成人心肌无保护的全脑缺血，因为这代表了 对心肌的“纯”缺血性挑战。 这项研究提供了一个 心脏停搏期间的实验基础。 四组 研究心脏：常氧对照，缺血20分钟， 常氧加5 mM丙酸盐，缺血20分钟加5 mM丙酸盐 缺血后丙酸。 常氧组的比较表明， 丙酸引起轻微（但不显著）减少， 速率-压力乘积，但是，像DCA一样，引起底物的主要变化 利用模式，抑制脂肪酸的利用， 乙酰乙酸，并刺激乳酸和未标记的氧化 源 回补作用大大增加。 缺血比较 组表明，丙酸导致显着改善， 缺血后心室功能 像DCA一样，它的代谢作用 虽然乙酰乙酸酯的使用量下降了， 显著地，乳酸盐和未标记来源的选择增加。 重要的是，回补显著上升（超过2倍） 与对照组相比。 （协作3）报告期： (09（1997年1月至1998年8月31日）

One of the goals of the current research is to develop and test alternate forms of substrate enhancements for use in cardioplegia or as adjuncts to myocardial protective strategies for open-heart surgery. Our examination of the effects of dichloroacetate (DCA) has been presented earlier in the Research Highlights section. We have also initiated the study of propionate which has a basis for improving cellular energetics that is supported in the literature, but has not been tested as an additive to cardioplegia. Our preliminary studies have been performed investigating this intervention in the setting of unprotected global ischemia in adult myocardium, as this represents a "pure" ischemic challenge to the myocardium. This study provides a basis for experiments during cardioplegic arrest. Four groups of hearts were studied: normoxic control, ischemia for 20 minutes, normoxia plus 5 mM propionate, and 20 mins of ischemia plus 5 mM propionate post-ischemia. Comparison of normoxic groups indicate that propionate caused a slight (but not significant) decrease in rate-pressure product, but, like DCA, caused major shifts in substrate utilization patterns, inhibiting utilization of fatty acids and acetoacetate, and stimulating oxidation of lactate and unlabeled sources. Anaplerosis was greatly increased. Comparison of ischemia groups indicate that propionate led to a significant improvement in post-ischemic ventricular function. Like DCA, its metabolic effects were relatively blunted, although acetoacetate use declined significantly and selection of lactate and unlabeled sources rose. Importantly, anaplerosis rose significantly (more than 2-fold) compared to the control group. (Collaborative 3) REPORT PERIOD: (09/01/97-08/31/98)