title: Vagal heart rate responses to chronic beta-blockade in human heart failure relate to cardiac norepinephrine spillover.
abstract: 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 baroreflex 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/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 beta-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.
authors.affiliation: 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.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kubo
authors.forename: John D
authors.initials: JD
authors.lastname: Parker
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Azevedo
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Atchison
authors.forename: Gary E
authors.initials: GE
authors.lastname: Newton
authors.forename: Peter
authors.initials: P
authors.lastname: Picton
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D017704:Baroreflex / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008790:Metoprolol / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol; D009638:Norepinephrine