Acute hemodynamic responses to sublingual nifedipine: dependence on left ventricular function.
Authors: P A Ludbrook, A J Tiefenbrunn, F R Reed, B E Sobel
Journal: Circulation (1982)

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 reduc- tion of LV afterload in patients with impaired baseline LV function.Nifedipine reduced myocardial oxygen requirements, enhanced diastolic performance and consequently improved systemic and pulmonary hemo- dynamics, 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 an- tagonists modify the movement of calcium ions across cell membranes -particularly in myocardium and vascular smooth muscle -by inhibiting the slow in- ward 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 induc- ing a negative inotropic effect.'Similarly, in vascular smooth muscle, calcium antagonists diminish smooth muscle contractility, which results in vasodilatation.8Although net consequences vary, combinations of these two effects appear to underlie the therapeutic