title: β-blockade restores muscle sympathetic rhythmicity in human heart failure.
abstract: BACKGROUND
  Muscle sympathetic nerve firing rate increases as chronic heart failure (CHF) progresses, yet its oscillation, particularly within the frequency range encompassing 0.13 Hz, diminishes. The current study tested the hypothesis that chronic therapy with lipophilic β-adrenoceptor antagonists augments the modulation of muscle sympathetic nerve activity variability (MSNAV) at this frequency range.
  
  
  RESULTS
  In 21 CHF angiotensin converting enzyme (ACE) inhibitor-treated patients (age: 53 ± 2, ejection fraction: 20 ± 2%), MSNA was recorded before and after 4 months of β-blockade with either metoprolol (up to 50mg b.i.d.) or carvedilol (up to 25mg b.i.d.). Harmonic MSNAV was assessed by coarse graining spectral analysis. Both drugs lowered heart rate similarly (-13 ± 2 beats/min; P < 0.001) but neither affected MSNA burst frequency (-7 ± 4 bursts/min, not significant). Before β-blockade, harmonic MSNA power in the region encompassing 0.13 Hz was essentially absent. Beta-blockade increased the mean values for total power (from 0.00 to 0.50 Hz; 5.2 ± 0.8 to 6.8 ± 1.2U(2); P < 0.001) and for harmonic MSNA spectral power across the 0.1-0.22 Hz frequency range (from 0.48 ± 0.10 to 1.50 ± 0.32 U(2), F = 12.2; P < 0.001). Both carvedilol and metoprolol had a similar effect.
  
  
  CONCLUSIONS
  In patients with CHF receiving ACE inhibitors, adding a β-adrenoceptor antagonist restores low and high frequency harmonic oscillations in MSNA. Beta-1 antagonism is sufficient to achieve this response. Augmented modulation of sympathetic outflow could contribute to the beneficial effects of β-blockade in CHF on sudden death and disease progression.
authors.affiliation: Division of Cardiology, Matsuyama Red Cross Hospital, Matsuyama, Japan. toskub@gmail.com
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kubo
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Azevedo
authors.forename: Gary E
authors.initials: GE
authors.lastname: Newton
authors.forename: Peter
authors.initials: P
authors.lastname: Picton
authors.forename: John D
authors.initials: JD
authors.lastname: Parker
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation*; D009864:Ontario; D010507:Periodicity; D010543:Peroneal Nerve / Q000187:drug effects* / Q000503:physiopathology; D011412:Propanolamines / Q000627:therapeutic use*; D012815:Signal Processing, Computer-Assisted; D013318:Stroke Volume / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol