Enhanced glucose oxidation in exercise-induced myocardial ischemia.
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BACKGROUND: In animal models, dichloroacetate (DCA) facilitates recovery from severe myocardial ischemia by stimulating glucose oxidation. OBJECTIVE: To evaluate the acute efficacy of DCA as a metabolic anti-ischemic intervention in patients with coronary artery disease (CAD) and exercise-induced myocardial ischemia in a clinical trial. METHODS: Double-blind, randomized, crossover comparison of single dose (50 mg/kg intravenously) DCA versus placebo on clinical and electrocardiographic variables in seven patients with single vessel CAD and 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 placebo tests and 37 DCA tests (not significant). Body surface potential maps (BSPM) of the decrease in the area under the ST curve from rest to peak exercise averaged -5096 microV's with DCA and -5159 microV's with placebo (not significant). BSPM at 1 and 5 mins postexercise also showed no differences in rate of ST integral recovery. CONCLUSIONS: In the transient regional model of human myocardial ischemia induced by dynamic exercise, the acute administration of the pyruvate dehydrogenase agonist DCA was not associated with clinical or electrocardiographic moderation of, nor accelerated recovery from, ischemia. Whether DCA or metabolically similar agents that enhance oxidative metabolism are beneficial in other ischemic settings, such as the no-flow states of acute ST elevation myocardial infarction or angioplasty, requires further systematic evaluation.
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