Effects of dichloroacetate on hemodynamic responses to dynamic exercise in dogs.
To determine whether lactic acid production contributes significantly to the cardiac responses to muscular dynamic exercise, we administered intravenous sodium dichloroacetate (32 mumol.kg-1.min-1), a pyruvate dehydrogenase activator that facilitates lactate metabolism via the tricarboxylic cycle, in 12 dogs during two graded levels of treadmill exercise. Similar exercise was carried out in nine normal dogs receiving equimolar doses of NaCl. In the latter group, arterial lactate increased progressively from 0.80 +/- 0.11 (SE) mmol/l at rest to 2.13 +/- 0.28 mmol/l by the end of exercise. In contrast, arterial lactate did not change significantly (0.98 +/- 0.12 to 0.95 +/- 0.11 mmol/l) during exercise in dogs receiving dichloroacetate infusion. Dichloroacetate infusion also reduced the increases in plasma norepinephrine, heart rate, and left ventricular contractile indexes that occurred during exercise, suggesting that the sympathetic cardiac stimulation occurring during exercise may be related to the production of lactic acid. However, dichloroacetate affected neither the net increase in cardiac output nor the relationship between total body oxygen consumption and cardiac output that occurred during exercise. Thus we conclude that lactic acid production is not essential to the increase in cardiac output that occurs during mild-to-moderate exercise.
Delehanty
J M
JM
Department of Medicine (Cardiology Unit), University of Rochester Medical Center, New York 14642.
Imai
N
N
Liang
C S
CS
D000222:Adaptation, Physiological; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D005082:Physical Exertion / Q000502:physiology*; D011773:Pyruvates / Q000097:blood; D019289:Pyruvic Acid
D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid; D003999:Dichloroacetic Acid; D009638:Norepinephrine; D004837:Epinephrine