The Rational for the Use of Ã -Blockers in the Treatment of Congestive Heart Failure.
Limited clinical data suggest that in particular types of congestive heart failure, the cautious use of low-dose Ã -blockers may be beneficial, despite the well-known cardiodepressant effect of these drugs. Downregulation of cardiac Ã -adrenoceptors has been demonstrated repeatedly in various forms of congestive heart failure. This phenomenon is caused by the long-term exposure of these receptors to endogenous noradrenaline (a Ã -adrenoceptor agonist), which is known to reach markedly elevated plasma concentrations in severe congestive heart failure. As but one example, the downregulation of Ã -adrenoceptors explains the well-known tachyphylaxis in the inotropic response to Ã -adrenoceptor agonists such as dobutamine. A beneficial effect of low-dose Ã -blockers has been shown for metoprolol and bucindolol given for several months. Most studies with such agents have been done in patients with severe congestive heart failure resulting from dilated cardiomyopathy. The beneficial effect of such therapy may be explained by Ã -adrenoceptor upregulation, thus allowing a better response to endogenous noradrenaline. Alternatively, the therapy may exert its effect by inhibiting tachycardia, which is known to accompany congestive heart failure.
van Zwieten
Pieter A.
PA
Professor and Chairman, Departments of Pharmacotherapy and Cardiology, Academic Medical Center, University of Amsterdam, The Netherlands.