METABOLIC EFFECTS OF CARDIOPLEGIA SUBSTRATE ENHANCEMENTS IN MYOCARDIUM

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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)