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

The acute and chronic effects of the dihydropyridine calcium antagonis t nisoldipine were studied in patients with chronic heart failure (LV EF < .35; peak VO2 < 25 ml/kg/min) caused by idiopathic or postinfarct ion 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 par t of the study because of excessive tachycardia or worsening heart fai lure, respectively; therefore, the final study group consisted of 12 p atients. Each patient was evaluated at rest, in the supine and sitting positions, and during maximal bicycle exercise, before and after acut e and chronic (2-3 months) oral nisoldipine therapy (20 mg bid). Plasm a levels of renin activity, aldosterone, norepinephrine, and epinephri ne were measured before and 1 hour after nisoldipine in 10 patients. C oncomitant therapy with digitalis and diuretics was kept constant thro ughout 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 l/min/m2, with a reduction of mean arterial pressure from 97 +/- 7 to 85 +/- 9 mmHg and systemic vascular resistance from 1 417 +/- 201 to 968 +/- 257 dynes sec/sec cm5 without significant chang es of right atrial and pulmonary pressures. Hemodynamic effects peaked 1 hour after its administration and persisted for 6 hours. Similar ch anges were observed in the resting sitting position. At maximal exerci se nisoldipine significantly increased cardiac index from 5.47 +/- 2.0 6 to 6.11 +/- 2.14 l/min/m2 and reduced mean arterial pressure from 11 5 +/- 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 sl ight but significant increase at rest (389 +/- 108 to 580 +/- 195 pg/m l) but not at peak exercise. Plasma renin activity and aldosterone did not significantly change after nisoldipine. Two patients did not tole rate chronic nisoldipine therapy because of pulmonary edema in one cas e and excessive tachycardia in the other and were withdrawn from the s tudy. After chronic therapy, the hemodynamics before nisoldipine admin istration were not significantly changed in comparison with baseline; the hemodynamic changes after nisoldipine were similar to those observ ed in the acute study. No significant change of exercise duration and peak oxygen consumption was observed after both acute and chronic niso ldipine therapy.