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European Journal of Heart Failure 2005 7(5):878-881; doi:10.1016/j.ejheart.2004.10.012
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© 2004 European Society of Cardiology

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

Toshihiko Kubo1, John D. Parker, Eduardo R. Azevedo, Deborah J. Atchison, Gary E. Newton, Peter Picton and John S. Floras*

Division of Cardiology, Mount Sinai Hospital and University Health Network Department of Medicine University of Toronto, 600 University Avenue Suite 1614, Toronto, Ontario, Canada, M5G 1X5

* Corresponding author. Tel.: +1 416 586 8704; fax: +1 416 586 8702. E-mial address: john.floras{at}utoronto.ca


  Abstract

We have documented a pre-junctional β-2 adrenoceptor mediated reduction in cardiac norepinephrine spillover (CNES) in heart failure patients receiving chronic β-blockade. Our present objective was to ascertain the consequence of this decrease for vagal heart rate (HR) regulation by determining CNES, arterial baroreflex sensitivity for HR (BRS) and arterial baroreflex modulation of muscle sympathetic nerve activity (MSNA) before and upon 4 months of β-blockade with either carvedilol or metoprolol. In 19 heart failure patients in sinus rhythm (age: 55±2 [mean±S.E.]; ejection fraction: 20±2%), β-blockade increased BRS from 4.8±0.9 to 7.9±1.3 ms/mm 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 β-blockade in heart failure augments reflex vagal control of HR at an efferent site of interaction involving blockade of cardiac sympathetic pre-junctional β-2 adrenoceptors that facilitate NE release.

Key Words: Adrenergic receptor blockers • Autonomic nervous system • Baroreflex • Heart rate variability • Receptors, adrenergic, beta • Sympathetic nervous system

Received May 10, 2004; Revised August 4, 2004; Accepted October 14, 2004

1 Current address: Matsuyama Red Cross Hospital, Masuyama Ehime 790-0826, Japan.


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