(Circulation. 1996;94:353-358.)
© 1996 American Heart Association, Inc.
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the Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Correspondence to John D. Parker, MD, Cardiovascular Division, Mount Sinai Hospital, Suite 1609, 600 University Ave, Toronto, Ontario, Canada M5G 1X5.
Background ß-Blockers may reduce cardiac sympathetic activity in patients with heart failure by antagonizing ß-adrenergic receptors that facilitate sympathetic outflow to the heart. To explore this possible effect of ß-blockade, we measured cardiac norepinephrine spillover responses in patients with heart failure after the acute administration of either propranolol, a nonselective ß-blocker, or metoprolol, a ß1-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 ß1-selective antagonist was associated with increased cardiac norepinephrine spillover. In contrast, the administration of a nonselective ß-blocker until similar hemodynamic end points were reached caused a reduction in norepinephrine spillover. This suggests that in patients with heart failure, nonselective ß-blockade may have favorable inhibitory effects on cardiac sympathetic activity.
Key Words: heart failure nervous system, autonomic norepinephrine ß-adrenergic antagonists
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