Acute effects of beta 1-selective and nonselective beta-adrenergic receptor blockade on cardiac sympathetic activity in congestive heart failure

Abstract

Background: beta-Blockers may reduce cardiac sympathetic activity in patients with heart failure by antagonizing beta-adrenergic receptors that facilitate sympathetic outflow to the heart. To explore this possible effect of beta-blockade, we measured cardiac norepinephrine spillover responses in patients with heart failure after the acute administration of either propranolol, a nonselective beta-blocker, or metoprolol, a beta 1-selective agent.

Methods and results: Eighteen patients were studied. Repeated intravenous doses of propranolol (0.5 mg; nine patients; left ventricular ejection fraction, 14 +/- 2%) or metoprolol (1.0 mg; nine patients; left ventricular ejection fraction, 18 +/- 2%) were administered until one of the following end points was reached: a 15% decrease in heart rate, left ventricular +dP/dt, or mean arterial blood pressure or a 5 mm Hg increase in left ventricular end-diastolic pressure. Propranolol (mean dose, 2.0 mg) and metoprolol (mean dose, 3.6 mg) caused similar reductions in heart rate, +dP/dt, and coronary sinus plasma flow. Cardiac norepinephrine spillover was reduced after propranolol (277 +/- 55 to 262 +/- 53 pmol/min, P < .05) but was increased after metoprolol (233 +/- 57 to 296 +/- 82 pmol/min, P < .05). In a comparison of the two groups, the decrease in spillover after propranolol was significantly different than the increase seen after metoprolol (P < .01).

Conclusions: The administration of a beta 1-selective antagonist was associated with increased cardiac norepinephrine spillover. In contrast, the administration of a nonselective beta-blocker until similar hemodynamic end points were reached caused a reduction in norepinephrine spillover. This suggests that in patients with heart failure, nonselective beta-blockade may have favorable inhibitory effects on cardiac sympathetic activity.