METABOLIC EFFECTS OF CARDIOPLEGIA SUBSTRATE ENHANCEMENTS IN MYOCARDIUM

当前研究的目标之一是开发和测试 用于心脏停搏液或心脏停搏液的替代形式的底物增强 作为心内直视手术心肌保护策略的补充 做手术。我们对二氯乙酸酯(DCA)的影响进行了检查 已在早些时候的研究要点部分介绍过。我们有 也开启了丙酸酯的研究，为今后的改进奠定了基础 细胞能量学，在文献中得到支持，但没有 已被测试为心脏停搏液的添加剂。我们的初步研究 已经对这一干预进行了调查， 成人心肌无保护的全脑缺血，因为这代表一种 “纯”缺血对心肌的挑战。这项研究提供了一个 在心脏停搏期间的实验基础。四组 对心脏进行研究：常氧对照组，缺血20分钟， 常氧加5 mM丙酸，缺血20分钟加5 mM 丙酸缺血后。常氧组的比较表明 丙酸引起了轻微(但不显著)的下降 率压产物，但与DCA一样，导致底物发生重大变化 利用模式，抑制脂肪酸的利用和 乙酰乙酸酯，并刺激乳酸和未标记的氧化 消息来源。退伍军人人数大大增加。缺血的比较 研究小组指出，丙酸能显著改善 缺血后的心功能。和DCA一样，它的新陈代谢效应 相对迟钝，尽管乙酰乙酸酯的使用量有所下降 乳酸盐和未标记来源的选择显著增加。 重要的是，复苏显著上升(超过2倍) 与对照组比较。(协作性3)报告期： (09/01/97-08/31/98)

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)