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(Circulation Research. 2008;102:633.)
© 2008 American Heart Association, Inc.

Report

Beneficial Effect of the Central Nervous System β-Adrenoceptor Blockade on the Failing Heart

Andrey Gourine, Svetlana I. Bondar, K. Michael Spyer, Alexander V. Gourine

From the Department of Physiology, University College London, United Kingdom.

Correspondence to Alexander V. Gourine, PhD, Department of Physiology, University College London, Gower St, London WC1E 6BT, United Kingdom. E-mail a.gourine{at}ucl.ac.uk

Heart failure patients are routinely given β-adrenoceptor antagonists (β-blockers), although the mechanism(s) underlying their beneficial effects is not fully resolved. It is not entirely clear how long-term application of negative inotropic compounds improves cardiac performance, slows remodeling processes, and decreases mortality. All β-blockers, which produce a beneficial effect in heart failure, have in common a high degree of lipophilicity and, therefore, have the ability to cross the blood–brain barrier. Here, we show that blockade of β-adrenoceptors directly in the brain (chronic intracerebroventricular administration of metoprolol) attenuates the progression of left ventricular remodeling in a rat model of myocardial infarction-induced heart failure. These results provide the first direct evidence that the action of certain β-blockers in the brain could contribute to their beneficial effect on the failing heart.

Key Words: central nervous system • β-blockers • heart failure • left ventricular remodeling • myocardial infarction