Effects of captopril versus milrinone therapy in modulating the adrenergic nervous system response to exercise in congestive heart failure.

The potential adverse consequences of increased adrenergic nervous system activity in patients with heart failure are now recognized. Modulation of the plasma noradrenaline response to submaximal exercise should be desirable. The long-term (9 weeks) effects of milrinone (10 mg 4 times a day) or captopril (50 mg 3 times a day) compared to placebo were evaluated in a double-blind crossover study, in 16 patients with stable, congestive heart failure receiving digoxin and furosemide. After treatment, clinical status (score range 0 to 14 points) improved significantly with both milrinone (4.4 +/- 0.5, p less than 0.01) and captopril (4.1 +/- 0.4, p less than 0.01). Plasma noradrenaline at rest was similar with both drugs and not significantly different from placebo. During submaximal exercise it increased significantly to 1,228 +/- 58 pg/ml with placebo and to 1,295 +/- 174 pg/ml with milrinone; this response was reduced significantly with captopril, to 820 +/- 100 pg/ml (p less than 0.01). Thus, long-term therapy with both captopril and milrinone improved the clinical score, but only captopril reduced the plasma noradrenaline response to submaximal exercise. These findings suggest that angiotensin-enzyme inhibition with captopril will modulate the adrenergic system response to daily activities in patients with chronic congestive heart failure and therefore could have additional salutary effects beyond vasodilatation.