ENHANCED GLUCOSE-OXIDATION IN EXERCISE-INDUCED MYOCARDIAL-ISCHEMIA

BACKGROUND: In animal models, dichloroacetate (DCA) facilitates recove ry from severe myocardial ischemia by stimulating glucose oxidation. O BJECTIVE: To evaluate the acute efficacy of DCA as a metabolic anti-is chemic intervention in patients with coronary artery disease (CAD) and exercise-induced myodcardial ischemia in a clinical trial. METHODS: D ouble-blind, randomized, crossover comparison of single dose (50 mg/kg intravenously) DCA versus placebo on clinical and electrocardiographi c variables in seven patients with single vessel CAD 34 patients with multiple vessel CAD during standard dynamic exercise testing. RESULTS: Blood pressure did not differ with placebo or DCA but mean heart rate was higher with DCA at rest (62 versus 59, P<0.004) and at 5 mins of recovery (78 versus 75, P<0.02). Exercise duration averaged 538 s with DCA and 534 s with placebo (not significant). Chest pain occurred in 14 patients in both tests, clinical ST depression occurred, in 34 plac ebo tests and 37 DCA tests (not significant). Body surface potential m aps (BSPM) of the decrease in the area under the ST curve from rest to peak exercise averaged -5096 mu V.s with DCA and -5159 mu V.s with pl acebo (not significant). BSPM at 1 and 5 mins postexercise also showed no differences in rate of ST integral recovery. CONCLUSIONS: In the t ransient regional model of human myocardial ischemia induced by dynami c exercise, the acute administration of the pyruvate dehydrogenase ago nist DCA was not associated with clinical or electrocardiographic mode ration of, nor accelerated recovery from, ischemia. Whether DCA or met abolically similar agents that enhance oxidative metabolism are benefi cial in other ischemic settings, such as the no flow states of acute S T elevation myocardial infarction or angioplasty, requires further sys tematic evaluation.