Circulatory improvement after hydralazine or isosorbide dinitrate administration in patients with heart failure. Effect on metabolic responses to submaximal exercise.

Hydralazine and isosorbide dinitrate can increase the cardiac output during submaximal exercise in patients with heart failure but whether this increase improves oxygen delivery to underperfused exercising muscle is uncertain. To investigate this question, we measured three systemic markers of skeletal muscle oxygen availability--exercise VO2, mixed venous lactate concentration and oxygen debt--during submaximal exercise in 15 patients with heart failure both before after hydralazine (nine patients) or isosorbide dinitrate (eight patients) administration. Hydralazine increased the cardiac output during exercise from 4.9 +/- 1.2 liter/min to 6.5 +/- 1.8 liter/min (p less than 0.01) but had no effect on exercise VO2 (control, 531 +/- 135 ml/min; hydralazine, 489 +/- 102 ml/min), peak lactate concentration (control, 18.3 +/- 4.2 mg/dl; hydralazine, 17.9 +/- 3.6 mg/dl) or oxygen debt (control, 474 +/- 213 ml; hydralazine, 465 +/- 170 ml) (all p greater than 0.10). Isosorbide dinitrate increased the cardiac output during exercise from 4.6 +/- 0.9 liter/min to 5.3 +/- 0.8 liter/min (p less than 0.01) but also did not change exercise VO2 (control, 488 +/- 62 ml/min; isosorbide, 473 +/- 44 ml/min), peak lactate concentration (control, 19.2 +/- 6.0 mg/dl; isosorbide, 21.4 +/- 8.2 mg/dl) or oxygen debt (control, 522 +/- 154 ml; isosorbide, 445 +/- 147 ml) (all p less than 0.10). We conclude that short-term administration of hydralazine or nitrates to patients with heart failure can substantially improve circulatory function during exercise but that this improvement probably does not enhance skeletal muscle nutritional flow.