Role of central sympathoexcitation in enhanced hypercapnic chemosensitivity in patients with heart failure.
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.
Yamada
Kunihiro
K
Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Asanoi
Hidetsugu
H
Ueno
Hiroshi
H
Joho
Shuji
S
Takagawa
Junya
J
Kameyama
Tomoki
T
Hirai
Tadakazu
T
Nozawa
Takashi
T
Inoue
Hiroshi
H
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
D013565:Sympatholytics; D002245:Carbon Dioxide; D016316:Guanfacine; D010100:Oxygen; D009638:Norepinephrine