with the technical assistance ofMichael R. Courtois, M.A.SUMMARY To characterize the acute effects of nifedipine on left ventricular (LV) systolic and diastolic function, we studied 32 patients stratified with respect to baseline LV function before and 30 minutes after nifedipine (20 mg sublingually) with a randomized, single-blind protocol. Nineteen patients received nifedipine and 13 received placebo. No change occurred in any variable after placebo. Nifedipine lowered left ventricular afterload, reflected by significant decreases in systolic, mean and diastolic arterial pressures of 13%, 10% and 17%, respectively. LV systolic pressure fell by 13%, ejection fraction, mean Vcf, mean normalized systolic ejection rate (MNSER), and the end-systolic pressure/volume (P-V) ratio increased by 14%, 41%, 25% and 19%, respectively, and cardiac index rose by 16% (p < 0.05 for each). Overall, diastolic LV function did not change; diastolic pressures, early diastolic relaxation, diastolic exponential P-V and P-V elasticity relations and end-diastolic stiffness remained constant. However, among patients stratified according to baseline LV function (group 1: end-diastolic volume < 90 ml/m2, end-diastolic pressure < 20 mm Hg; group 2: enddiastolic volume > 90 ml/M2, end-diastolic pressure > 20 mm Hg) striking differences were evident. In group 2 patients, nifedipine decreased LV systolic and end-diastolic pressures, while LV end-diastolic and systolic volumes, and systemic and pulmonary vascular resistance all declined significantly, by 13%, 27%, 41% and 52%, respectively. Enhancement of ejection fraction (34%), Vcf (46%) and MNSER (41%) in group 2 patients was substantially more prominent than that in patients with normal baseline LV function (9%, 35% and 15%, respectively). Relaxation and diastolic stiffness properties were insignificantly changed in both groups, but the diastolic exponential P-V relation was displaced downward by nifedipine in patients with impaired baseline ventricular function, and cardiac output was increased by 25%, compared with a negligible change (3%) in group 1 patients.These results show that nifedipine has significant, clinically favorable effects due predominantly to reduction of LV afterload in patients with impaired baseline LV function. Nifedipine reduced myocardial oxygen requirements, enhanced diastolic performance and consequently improved systemic and pulmonary hemodynamics, LV ejection function and cardiac output. NIFEDIPINE appears to relieve variant' and typical angina pectoris,2 though its mechanisms have not been completely defined. Nifedipine and other calcium antagonists modify the movement of calcium ions across cell membranes -particularly in myocardium and vascular smooth muscle -by inhibiting the slow inward calcium channel. In cardiac muscle, calcium activates ATPase of the contractile proteins. Thus, calcium antagonists inhibit excitation-contraction coupling, favoring relaxation of the muscle and inducing a negative inotropic effect.' Similarly, in vascular smooth muscle, ca...

No abstract

No abstract

Either augmentation or impairment of left ventricular function has previously been reported in different patients, in response to isometric exercise. To identify the mechanisms associated with these disparate responses, the effects of submaximal sustained handgrip upon left ventricular systolic and diastolic properties were studied in 29 patients during diagnostic catheterization. In 16 patients (group I), ejection fraction, mean Vcf, and the mean systolic ejection rate remained constant, while the ratio of peak systolic pressure to end systolic volume increased significantly from 2.81 +/- 0.6 to 3.17 +/- 0.6 ml/mm Hg. In 13 patients (group II) ejection fraction declined from 0.6 +/- 0.03 to 0.51 +/- 0.03, Vcf from 0.96 +/- 0.09 to 0.85 +/- 0.09 circ/sec, mean normalized systolic ejection rate from 1.79 +/- 0.1 to 1.50 +/- 0.09 sec-1, and the peak systolic pressure to end systolic volume ratio from 2.23 +/- 0.3 to 1.99 +/- 0.3 (p less than 0.05 for each). Systemic arterial mean pressure increased similarly by 19% and 21% in groups I and II, respectively (p less than 0.05 for each). Systemic vascular resistance increased significantly by 23% in group I and by 5% in group II (p less than 0.05). Left ventricular end diastolic volume declined from 85.4 +/- 7 to 77.3 +/- 11 ml/m2 in group I, while end diastolic and end systolic volumes increased by 13% and 35%, respectively in group II (p less than 0.05 for each). In both groups, baseline exponential pressure-volume relations were similar, though higher intercepts on the pressure-volume relations upon the Y-axis suggested greater "diastolic tone," and steeper volume-normalized pressure-volume elasticity relations indicated "stiffer" left ventricular chambers in group II patients. While the incidence of coronary artery disease was similar, both the severity and extent of left ventricular asynergy were greater in group II patients. We conclude that dilatation and deterioration of left ventricular ejection function in response to isometric exercise are causally related to, and comprise a useful predictor of, severe underlying left ventricular asynergy and impaired chamber distensibility.