Role of central sympathoexcitation in enhanced hypercapnic chemosensitivity in patients with heart failure

Yamada, Kunihiro; Asanoi, Hidetsugu; Ueno, Hiroshi; Joho, Shuji; Takagawa, Junya; Kameyama, Tomoki; Hirai, Tadakazu; Nozawa, Takashi; Inoue, Hiroshi

doi:10.1016/j.ahj.2004.05.030

« Previous Next »American Heart Journal
Volume 148, Issue 6 , Pages 964-970, December 2004

Role of central sympathoexcitation in enhanced hypercapnic chemosensitivity in patients with heart failure☆

Kunihiro Yamada, MD
- Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Hidetsugu Asanoi, MD
- Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
- Reprint requests: Hidetsugu Asanoi, MD, Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani Toyama 930-0194, Japan
Hiroshi Ueno, MD
- Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Shuji Joho, MD
- Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Junya Takagawa, MD
- Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Tomoki Kameyama, MD
- Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Tadakazu Hirai, MD
- Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Takashi Nozawa, MD
- Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Hiroshi Inoue, MD
- Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan

Received 9 August 2003; accepted 2 May 2004.

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 α 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 α 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.