title: Role of central sympathoexcitation in enhanced hypercapnic chemosensitivity in patients with heart failure.
abstract: BACKGROUND
  Enhanced central hypercapnic chemosensitivity is known to mediate excessive exercise ventilation and to indicate a poor prognosis in patients with chronic heart failure. The present study was designed to elucidate the role of central sympathetic activity in the enhancement of hypercapnic chemosensitivity.
  
  
  METHODS
  Central hypercapnic chemosensitivity and plasma norepinephrine were measured in 99 patients with chronic heart failure. In 40 patients, the alpha index was derived from simultaneous analysis of R-R interval and systolic blood pressure variability. The effects of a central sympatholytic agent, guanfacine (0.25 mg/day), on hypercapnic chemosensitivity and exercise ventilatory response were studied in 20 of these patients.
  
  
  RESULTS
  Hypercapnic chemosensitivity was enhanced in 76% of the patients and correlated significantly with plasma norepinephrine levels (r = 0.49, P < .01) at rest. There was a significant inverse relationship between central chemosensitivity and the alpha index (r = -0.41, P < .01). Guanfacine significantly reduced plasma norepinephrine levels by 29% (P < .01) and chemosensitivity by 31% (P < .01). The beneficial effect of central sympathoinhibition with guanfacine was observed specifically in patients who had enhanced chemosensitivity prior to drug administration. Similarly, the patients with excessive exercise ventilation showed a greater reduction in exercise ventilation with this agent.
  
  
  CONCLUSIONS
  The present findings suggest that central sympathoexcitation could play an important role in the pathogenesis of enhanced hypercapnic chemosensitivity and a resultant increase in exercise ventilation in chronic heart failure.
authors.affiliation: Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamada
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Asanoi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Shuji
authors.initials: S
authors.lastname: Joho
authors.forename: Junya
authors.initials: J
authors.lastname: Takagawa
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kameyama
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Hirai
authors.forename: Takashi
authors.initials: T
authors.lastname: Nozawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
mesh_terms: D002245:Carbon Dioxide / Q000097:blood / Q000502:physiology; D004417:Dyspnea / Q000209:etiology; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D016316:Guanfacine / Q000494:pharmacology; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006935:Hypercapnia / Q000150:complications / Q000503:physiopathology*; D006985:Hyperventilation / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010100:Oxygen / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013565:Sympatholytics / Q000494:pharmacology
chemical_list: D013565:Sympatholytics; D002245:Carbon Dioxide; D016316:Guanfacine; D010100:Oxygen; D009638:Norepinephrine