Vagal heart rate responses to chronic beta-blockade in human heart failure relate to cardiac norepinephrine spillover

We have documented a pre-junctional beta-2 adrenoceptor mediated reduction in cardiac norepinephrine spillover (CNES) in heart failure patients receiving chronic beta-blockade. Our present objective was to ascertain the consequence of this decrease for vagal heart rate (HR) regulation by determining CNES, arterial baroreflcx sensitivity for HR (BRS) and arterial baroreflex modulation of muscle sympathetic nerve activity (MSNA) before and upon 4 months of beta -blockade with either carvedilol or metoprolol. In 19 heart failure patients in sinus rhythm (age: 55 +/- 2 [mean +/- S.E.]; ejection fraction: 20 +/- 2%), beta -blockade increased BRS from 4.8 +/- 0.9 to 7.9 +/- 1.3 ms/min Hg (P < 0.005) but had no effect on arterial baroreflex modulation of MSNA. Changes in CNES and BRS were inversely related (r=-0.52; n=16, P < 0.05). Chronic blockade in heart failure augments reflex vagal control of HR at an efferent site of interaction involving blockade of cardiac sympathetic pre-junctional beta-2 adrenoceptors that facilitate NE release. (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.