HEMODYNAMIC, INOTROPIC AND DROMOTROPIC EFFECTS OF CALCIUM-ANTAGONISTS AT REST AND DURING EXERCISE IN HEALTHY-SUBJECTS

The hemodynamic, inotropic and dromotropic effects of three calcium antagonists both at rest and during exercise were compared in 15 healthy subjects (mean age 25 ± 6 years). After a single dose of diltiazem 120 mg, verapamil 160 mg and nifedipine 20 mg in a double-blind, cross-over, randomized manner the following measurements were performed 1, 2, 4 and 6 h after drug intake and were compared with the predrug values: blood pressure, electrocardiogram, systolic time intervals, venous occlusion plethysmography and an orthostatic test. Resting diastolic blood pressure decreased significantly after diltiazem and nifedipine. The P-Q interval was prolonged maximally by 46 ms (p < 0.001) after verapamil, by 19 ms (p < 0.01) after diltiazem but remained unchanged after nifedipine. Calculated peripheral resistance (mean blood pressure/arterial flow) decreased by 23-29% after all three drugs (p < 0.01); the effect peaked at 1 h after nifedipine and at 4 h after diltiazem and verapamil. Preejection period (PEP) decreased significantly by 10-15% after all three drugs. The orthostatic test induced an immediate increase in heart rate of 26 beats per minute (bpm) after nifedipine (p < 0.001), 20 bpm after verapamil (p < 0.05) and 16 bpm after diltiazem (n.s.), the predrug increase being 10-12 bpm. During exercise at an average heart rate of 142 bpm neither blood pressure nor heart rate changed after diltiazem or verapamil compared with predrug values. Nifedipine decreased exercise systolic and diastolic blood pressures compared with predrug values by 4-5 mm Hg (p < 0.05) and increased heart rate by 12 bpm (p < 0.001). PEP, recorded during exercise, remained unchanged after all three drugs compared with predrug values. We conclude that, with the doses used (1) the reported negative inotropic effect in vitro of diltiazem and verapamil is compensated by a decrease in afterload in healthy subjects, (2) diltiazem has, in contrast to nifedipine, negligible orthostatic effects and (3) only nifedipine has any significant effect on exercise hemodynamics.