Acute and chronic effects of the dihydropyridine calcium antagonist nisoldipine on the resting and exercise hemodynamics,neurohumoral parameters,and functional capacity of patients with chronic heart failure

Summary The acute and chronic effects of the dihydropyridine calcium antagonist nisoldipine were studied in patients with chronic heart failure (LV EF<.35; peak VO₂<25 ml/kg/min) caused by idiopathic or postinfarction cardiomyopathy. The study group initially consisted of 16 patients; two patients were excluded from the acute study due to side effects of the drug and two more patients were excluded during the chronic part of the study because of excessive tachycardia or worsening heart failure, respectively; therefore, the final study group consisted of 12 patients. Each patient was evaluated at rest, in the supine and sitting positions, and during maximal bicycle exercise, before and after acute and chronic (2–3 months) oral nisoldipine therapy (20 mg bid). Plasma levels of renin activity, aldosterone, norepinephrine, and epinephrine were measured before and 1 hour after nisoldipine in 10 patients. Concomitant therapy with digitalis and diuretics was kept constant throughout the study. At rest, in the supine position, nisoldipine (20 mg orally) induced an acute increase of cardiac index from 2.87±0.52 to 3.93±1.52 1/min/m², with a reduction of mean arterial pressure from 97±7 to 85±9 mmHg and systemic vascular resistance from 1417±201 to 968±257 dynes sec/sec cm⁵ without significant changes of right atrial and pulmonary pressures. Hemodynamic effects peaked 1 hour after its administration and persisted for 6 hours. Similar changes were observed in the resting sitting position. At maximal exercise nisoldipine significantly increased cardiac index from 5.47±2.06 to 6.11±2.14 1/min/m² and reduced mean arterial pressure from 115±13 to 106±16 mmHg, systemic vascular resistances from 1008±333 to 770±234 dynes sec cm⁵, and pulmonary wedge pressure from 37±11 to 30±13 mmHg. Plasma norepinephrine levels showed a slight but significant increase at rest (389±108 to 580±195 pg/ml) but not at peak exercise. Plasma renin activity and aldosterone did not significantly change after nisoldipine. Two patients did not tolerate chronic nisoldipine therapy because of pulmonary edema in one case and excessive tachycardia in the other and were withdrawn from the study. After chronic therapy, the hemodynamics before nisoldipine administration were not significantly changed in comparison with baseline; the hemodynamic changes after nisoldipine were similar to those observed in the acute study. No significant change of exercise duration and peak oxygen consumption was observed after both acute and chronic nisoldipine therapy.