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Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease
T J Wargovich1, R G MacDonald, J A Hill
1Department of Medicine, University of Florida, Gainesville 32610.
Insights
Dichloroacetate (DCA) enhances myocardial efficiency and lactate utilization in coronary artery disease patients. This study shows DCA improves stroke volume and vasodilation, benefiting cardiac function.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Dichloroacetate (DCA) activates pyruvate dehydrogenase, potentially improving energy metabolism.
- Limited data exists on DCA's effects in patients with coronary artery disease (CAD).
Purpose of the Study:
- To investigate the hemodynamic and metabolic effects of DCA in patients with CAD and angina.
- To assess DCA's impact on myocardial substrate utilization and efficiency.
Main Methods:
- Nine patients with CAD undergoing catheterization received intravenous DCA.
- Systemic and coronary hemodynamic and metabolic measurements were recorded before and during DCA administration.
Main Results:
- DCA increased left ventricular stroke volume and decreased systemic vascular resistance.
- Myocardial efficiency index significantly improved, while myocardial oxygen consumption remained unchanged.
- Myocardial lactate consumption was maintained at lower arterial lactate concentrations.
Conclusions:
- DCA stimulates myocardial lactate utilization at lower arterial concentrations in CAD patients.
- DCA causes peripheral vasodilation, augments stroke volume, and enhances myocardial efficiency.
- DCA shows potential therapeutic benefits for patients with coronary artery disease.
Abstract:
Dichloroacetate (DCA), which activates pyruvate dehydrogenase, has the potential to enhance carbohydrate and lactate utilization in animals, but data from patients with coronary artery disease are lacking. Accordingly, 9 patients (ages 49 to 72 years) with angina and coronary artery disease undergoing catheterization were studied. Systemic and coronary hemodynamic and metabolic measurements were made before and during DCA administration (mean dose 35 mg/kg, intravenously). DCA increased left ventricular (LV) stroke volume from 77 +/- 7 to 87 +/- 7 ml and decreased systemic vascular resistance from 1,573 +/- 199 to 1,319 +/- 180 dynes.s.cm-5 (both, p less than 0.01). There were no significant changes in heart rate, mean aortic pressure, LV end-diastolic pressure, LV dP/dt max, coronary sinus flow, coronary resistance or myocardial oxygen consumption, but myocardial efficiency index (LV work/myocardial oxygen consumption) improved from 24 to 32% (p less than 0.05). Myocardial lactate consumption was maintained (21 +/- 8 vs 19 +/- 11 X 10(-3) mEq/min, p is not significant at p less than or equal to 0.05 level) at a lower arterial lactate concentration (0.72 +/- 0.09 to 0.47 +/- 0.08 mEq/liter, p less than 0.05). DCA appears to stimulate myocardial lactate utilization at a lower arterial concentration, cause peripheral vasodilation, augment stroke volume and enhance myocardial efficiency in patients with coronary artery disease.