Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease.
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.
Wargovich
T J
TJ
Department of Medicine, University of Florida, Gainesville 32610.
MacDonald
R G
RG
Hill
J A
JA
Feldman
R L
RL
Stacpoole
P W
PW
Pepine
C J
CJ
D000085:Acetates / Q000627:therapeutic use*; D000368:Aged; D006328:Cardiac Catheterization; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged
D000085:Acetates; D007773:Lactates; D003999:Dichloroacetic Acid