Dichloroacetate enhances myocardial functional and metabolic recovery following global ischemia

Abstract

This study was undertaken to determine the effect of dichloroacetate (DCA) on myocardial functional and metabolic recovery following global ischemia. Sixteen isolated rabbit hearts were subjected to 120 minutes of mildly hypothermic (34°C) cardioplegic arrest with multi-dose, modified St. Thomas' cardioplegia. Following ischemia, hearts were reperfused with either a physiologic salt solution (PSS) as controls, (CON, N = 10), or PSS containing DCA (DCA, N = 6) at a concentration of 1 mmol/L. Functional and metabolic indices were determined at baseline and at 15, 30, and 45 minutes of reperfusion. Results were analyzed using analysis of variance (ANOVA, Sheffe F test) and significance was defined as P < 0.05. Functional recovery was significantly better in hearts reperfused with DCA. Developed pressure (DP) recovered to 62 ± 4% of baseline in DCA hearts, compared to 37 ± 8% in CON hearts. Recovery of dP/dt was also improved in DCA versus CON hearts (67 ± 5 v43 ± 10%). Coronary blood flow was not different between groups either at baseline or during reperfusion, but myocardial oxygen consumption (MVO 2) was increased in the DCA versus CON hearts (71 ± 10% of baseline, v 51 ± 19%). Diastolic compliance during reperfusion was improved in those hearts receiving DCA, as was myocardial mechanical use efficiency (DP/MVO 2). Correction of myocardial tissue pH to baseline values was similar in both groups, indicating that the beneficial effect on functional recovery seen with DCA was not solely related to amelioration of acidosis. The enhanced myocardial function and improved metabolic status noted with DCA may result from increased oxidative phosphorylation due to altered pyruvate dehydrogenase (PDH) activity.