Elsevier

American Heart Journal

Volume 148, Issue 6, December 2004, Pages 964-970
American Heart Journal

Clinical investigations: Congestive heart failure
Role of central sympathoexcitation in enhanced hypercapnic chemosensitivity in patients with heart failure

https://doi.org/10.1016/j.ahj.2004.05.030Get rights and content

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.

Section snippets

Study patients

Ninety-nine patients with stable chronic heart failure (77 men, 22 women) were studied (Table I). The causes of cardiac disease were dilated cardiomyopathy in 51 patients, prior myocardial infarction in 12, valvular heart disease in 15, and miscellaneous causes in 21. Functional status was New York Heart Association (NYHA) functional class I in 47 patients, class II in 18, and class III in 34. Specific activity scales7 obtained from interviewing daily physical activities were 5.6 ± 1.8

Hypercapnic chemosensitivity and functional impairment

The relationship between hypercapnic chemosensitivity and ventilatory, cardiac, and neurohumoral variables is summarized in Table II.Although hypercapnic chemosensitivity did not correlate with exercise capacity assessed by peak Vo2 and the anaerobic threshold, there was a significant inverse correlation between chemosensitivity and ordinary physical activity assessed by the specific activity scale. A close positive correlation was found between chemosensitivity and exercise ventilatory

Discussion

The present study revealed the causative relationship between sympathetic nerve activity and enhanced hypercapnic chemosensitivity in patients with chronic heart failure. Another important finding of this study is that the effect of the sympatholytic agent on hypercapnic chemosensitivity depends on the baseline chemosensitivity. Patients with a higher hypercapnic chemosensitivity benefited more from the central sympatholytic agent guanfacine. Similarly, central sympathoinhibition resulted in a

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    Supported by Grant-in-Aid for General Scientific Research No 13670697 from the Ministry of Education, Science and Culture of Japan.

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