doi: 10.1161/hc4301.098282
(Circulation. 2001;104:2194.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Nonselective Versus Selective ß-Adrenergic Receptor Blockade in Congestive Heart Failure
Differential Effects on Sympathetic Activity
From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Ontario, and the Section of Cardiology, Department of Medicine, St Boniface Hospital, University of Manitoba (E.R.A.), Winnipeg, Canada.
Correspondence to John D. Parker, MD, Associate Professor of Medicine, Division of Cardiology, Mount Sinai Hospital, University of Toronto, 600 University Ave, Suite 1609, Toronto, Ontario, Canada M5G-1X5. E-mail jdp{at}inforamp.net
Background— Activation of the sympathetic nervous system has important prognostic implications in chronic heart failure. Nonselective versus selective ß-adrenergic receptor antagonists may have differential effects on norepinephrine release from nerve terminals mediated by prejunctional ß2-adrenergic receptors.
Methods and Results —— Thirty-six patients with chronic heart failure were randomized to the nonselective ß-blocker carvedilol or the selective ß-blocker metoprolol (double-blind). Measurements of hemodynamics and cardiac and systemic norepinephrine spillover as well as microneurographic recordings of muscle sympathetic nerve traffic were made before and after 4 months of therapy. In the carvedilol group (n=17), there were significant reductions in both total body (-1.7±0.5 nmol/min, P<0.01) and cardiac norepinephrine spillover (-87±29 pmol/min, P<0.01). By contrast, in the metoprolol group (n=14), there were no significant changes in total body or cardiac norepinephrine spillover. Responses in the carvedilol group were significantly different from those observed in the metoprolol group (P<0.05). Both agents caused a reduction in heart rate and increases in pulse pressure, although mean arterial pressure did not change. Importantly, microneurographic measures of sympathetic nerve traffic to skeletal muscle did not change in either group.
Conclusions— Therapy with carvedilol caused significant decreases in systemic and cardiac norepinephrine spillover, an indirect measure of norepinephrine release. Such changes were not observed in patients treated with metoprolol. There was no effect of either agent on sympathetic efferent neuronal discharge to skeletal muscle. These findings suggest that carvedilol, a nonselective ß-blocker, caused its sympathoinhibitory effect by blocking peripheral, prejunctional ß-adrenergic receptors.
Key Words: heart failure • receptors, adrenergic, beta • nervous system, autonomic • norepinephrine
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