Effect of flecainide on regional left ventricular wall motion after acute intravenous, acute oral and chronic oral administration late after coronary artery bypass grafting.

Epicardial marker motion was measured in 14 patients before flecainide administration, immediately after an intravenous dose of 2 mg/kg over 15 minutes (maximum 150 mg) and 15 minutes thereafter. Platinum epicardial markers had been implanted more than 4 years earlier at the time of coronary artery bypass grafting. Maximal and minimal marker separation (Lmax and Lmin) during the cardiac cycle were measured and regional shortening fraction (Lmax - Lmin)/Lmax) was determined as a percentage. After intravenous flecainide, a significant increase in end-diastolic (immediately after 2.8%; after 15 minutes 2.1%) and end-systolic (3.6% and 3.2%) regional dimensions was observed, together with a decrease in regional myocardial shortening (9.3% and 9.0%). One week later, after a single oral dose of 200 mg of flecainide, Lmax and Lmin had increased 2.4% and 2.7%, while regional myocardial shortening did not differ significantly from baseline values. In 10 patients measurements were repeated after 6 weeks of chronic oral treatment with 300 mg/day. Despite plasma flecainide levels similar to those after intravenous administration, no significant changes in end-diastolic and end-systolic dimensions or regional shortening fraction were observed. Thus, acute intravenous or oral flecainide administration increases regional end-diastolic and end-systolic dimensions, but only intravenous administration decreases regional shortening fraction. Values during chronic administration indicate that regional myocardial function is more affected at the time of rising or acutely changing flecainide plasma levels than when stable plasma levels are achieved.

The haemodynamic effects of nifedipine, verapamil and diltiazem in patients with coronary artery disease. A review.

Of the 3 most widely used calcium antagonists--nifedipine, verapamil and diltiazem--nifedipine is the most potent arterial vasodilator. Increases in cardiac output and coronary blood flow following nifedipine administration result in part from the afterload reduction. Reflex adrenergic stimulation produces an increase in heart rate and masks a direct inhibitory effect on myocardial contractility. The negative inotropic action of nifedipine is observed during intracoronary administration or may be made apparent by concurrent beta-blocker therapy. While verapamil is also a potent vasodilator, negative inotropic and dromotropic properties are more apparent in therapeutically used dosages. Reflex sympathetic activation is also triggered by verapamil, with an offsetting of the negative inotropic effects such that little change in cardiac output results. A decrease in myocardial oxygen consumption, with or without a decrease in coronary sinus blood flow, has regularly been observed following verapamil administration. Reduced oxygen demand appears to be a major mechanism of its antianginal effect. The heart rate X systolic pressure product is decreased both by the fall in arterial pressure and, particularly after oral administration, by a decrease in heart rate. Diltiazem produces similar haemodynamic and electrophysiological effects to those of verapamil but has less potency in inducing arterial dilatation and more of a tendency to slow the heart rate. Diltiazem does not appear to cause significant increases in coronary blood flow or bring about improvement in ejectional and isovolumic indices of myocardial contraction - evidence of its intrinsic negative inotropic effect.

Acute effects of intravenous nisoldipine on left ventricular function and coronary hemodynamics.

The hemodynamic effects of nisoldipine were investigated in 16 patients with suspected coronary artery disease who underwent routine cardiac catheterization. Nisoldipine was given intravenously in a dose of 6 micrograms/kg over 3 minutes and measurements made before and after drug administration during spontaneous and matched atrial paced heart rate. During sinus rhythm, nisoldipine produced a significant increase in heart rate (19%, p less than 10(-5]. Left ventricular systolic pressure decreased 28% (p less than 10(-6) and left ventricular end-diastolic pressure did not change significantly (5%, difference not significant). Coronary sinus and great cardiac vein blood flow increased by 21% (p less than 0.02) and 25% (p less than 0.005), respectively, after nisoldipine administration. Simultaneously, mean aortic pressure decreased 33% (p less than 10(-6]; consequently, the global and regional coronary vascular resistances decreased by 50% (p less than 10(-4]. The decreases in global (-8%) and regional (-4%) myocardial oxygen consumption did not reach statistical significance. A 6% (not significant) increase in end-diastolic volume and an 11% (p less than 0.002) decrease in end-systolic volume resulted in an increase of 21% in stroke volume (p less than 10(-4] with a consistent increase in ejection fraction (+16%, p less than 10(-5]. Total systemic vascular resistance was reduced by 30% (p less than 0.0002). During spontaneous heart rate and matched atrial pacing, the time constant of isovolumic relaxation as assessed by a biexponential model, was significantly shortened.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-anginal, electrophysiologic and hemodynamic effects of combined beta-blocker/calcium antagonist therapy.

Nitrates and beta-blockers have been the mainstay in the therapy of chronic stable angina pectoris for many years. Since an important number of patients remains symptomatic, new potent anti-ischemic agents like the calcium antagonists fulfil a great clinical need. Combined therapy with beta-blockers and calcium antagonists is attractive, since both classes of drugs have differing and eventually complementary modes of action. On the other hand, both have direct negative inotropic and chronotropic effects. We reviewed the anti-anginal, electrophysiologic and hemodynamic effects of combined treatment with a beta-blocker and verapamil or nifedipine. Combined therapy provides greater symptomatic relief than monotherapy with beta-blockers or slow channel blockers alone. While incidental adverse negative inotropic and chronotropic interactions have been reported, particularly when verapamil is involved, their hemodynamic interplay appears beneficial rather than detrimental in the majority of patients. Indeed, combined therapy is effective and safe, at least when a preserved or only moderately impaired left ventricular function is present. However, caution must be exercised in patients with more impaired left ventricular function, and combined therapy with verapamil must be avoided when conduction disturbances are likely to occur.