Temporal and Spatial Dynamics in the Regulation of Myocardial Metabolism During the Ischemia-Reperfusion Process

Although cardiac metabolic adaptation has been observed in response to the ischemia-reperfusion, the specific temporal and spatial changes occurring in the main regulators of myocardial glucolipid metabolism in the infarcted heart have not been fully characterized. Myocardial infarction (MI) was induced in female swine by transient coronary occlusion. The study design consisted of one control and four MI groups (no reperfusion, 1 min, 1 week, and 1 month after reperfusion). Metabolites obtained from the coronary sinus were determined at baseline, during ischemia, and after coronary reperfusion. mRNA expression of genes related to beta-oxidation and glucose transport were quantified in the five experimental groups and in three myocardial regions (infarcted, adjacent, and remote). In the coronary sinus, reduced glucose and increased lactate levels were detected during ischemia and soon after reperfusion. However, non-esterified fatty acids increased during reperfusion. A general upregulation of genes implicated in glycolysis and beta-oxidation occurred during ischemia and few minutes after reperfusion. Contrarily, heightened mRNA expression of glucose transporters and decay in regulators of beta-oxidation were observed one week after coronary reperfusion. Glycolysis and beta-oxidation are activated during ischemia and few minutes after coronary reopening, while a shift from beta-oxidation to glycolysis is evidenced a few days afterwards.