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(Circulation. 2003;107:2395.)
© 2003 American Heart Association, Inc.

Editorial

How Do ß-Blockers Improve Ventricular Function in Patients With Congestive Heart Failure?

William H. Barry, MD; E. Michael Gilbert, MD

From the Cardiology Division, University of Utah Health Sciences Center, Salt Lake City.

Correspondence to William H. Barry, MD, Division of Cardiology, University of Utah Health Sciences Center, 50 North Medical Dr, Salt Lake City, UT 84132. E-mail whbarry@med.utah.edu

Key Words: Editorials • heart failure • ventricles • receptors, adrenergic, beta

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The binding of ß-adrenergic agonists such as norepinephrine and isoproterenol to the ß-1 adrenergic receptor (AR) in the sarcolemma of the ventricular myocyte increases intracellular levels of cAMP via G_s protein-induced stimulation of adenyl cyclase. cAMP activates protein kinase A (PKA), which causes phosphorylation of proteins involved in Ca²⁺ homeostasis, such as phospholamban and the L-type Ca²⁺ channel, increasing the intracellular calcium ion concentration ([Ca²⁺]_i) transient, and thus causing a positive inotropic effect. It is now very well established that patients with congestive heart failure due to ischemic or idiopathic dilated cardiomyopathy are in a hyperadrenergic state.¹ Treatment of these patients with ß-adrenergic receptor-blocking drugs reduces morbidity and mortality,² improves ventricular function, and reverses pathological remodeling.³ Clinical and experimental animal studies have suggested a number of mechanisms by which chronic exposure to this class of drugs, which have a negative inotropic effect in normal myocardium, could have an apparently paradoxical beneficial effect in failing myocardium.

See p 2459

Seminal work by Bristow and associates⁴ showed that ß-1 AR density is reduced in the failing myocardium, and receptor density is increased by treatment with some ß-AR blockers.⁵ An increase in ß-receptor density may restore toward normal an available positive inotropic reserve in patients with heart failure. In isolated myocytes, a cytotoxic effect of prolonged adrenergic stimulation can be demonstrated,⁶ suggesting that ß-blockade may reduce a deleterious effect of the chronic hyperadrenergic state on myocyte survival. Treatment with ß-blockers also slows the heart rate. Because failing myocardium displays a decrease . . . [Full Text of this Article]

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