Effect of acetazolamide on chemosensitivity, Cheyne-Stokes respiration, and response to effort in patients with heart failure.

Abstract

Increased chemosensitivity to hypoxia and hypercapnia, together with a prolonged circulatory time, are the main determinants of Cheyne-Stokes (C-S) respiration in heart failure. To evaluate the effect of acetazolamide, a carbonic anhydrase inhibitor, on chemosensitivity and respiratory dynamics in patients with heart failure with C-S respiration, 12 patients (mean age 62 ± 9 years, mean left ventricular ejection fraction 24 ± 9%) and C-S respiration (mean apnea-hypopnea index 23 ± 13) who underwent 4 consecutive days of oral acetazolamide treatment (250 mg twice daily) were enrolled in this study. Assessment of chemosensitivity to hypoxia and hypercapnia, cardiopulmonary stress testing, 24-hour cardiorespiratory polygraphy, and neurohormonal characterization were performed at baseline and at the end of treatment. Acetazolamide improved central apneas (apnea-hypopnea index 23 ± 13 to 15 ± 9, p = 0.012) and the percentage of time spent below an arterial oxyhemoglobin saturation of 90% (16 ± 23% to 10 ± 18%, p = 0.005). Chemosensitivity to hypoxia was blunted (1.03 ± 0.69 to 0.78 ± 0.55 L/min/mm Hg, p = 0.032), while chemosensitivity to hypercapnia increased after acetazolamide (1.27 ± 0.71 to 1.54 ± 0.78 L/min/% arterial oxygen saturation, p = 0.023); patients achieved a lower workload (90 ± 30 to 81 ± 30 W, p <0.001), with no differences in peak oxygen consumption, while there was an increment in the regression slope relating minute ventilation to carbon dioxide output (39 ± 10 to 43 ± 9, p = 0.010). In conclusion, in patients with heart failure, acetazolamide diminishes C-S respiration and improves oxyhemoglobin saturation, likely by decreasing chemosensitivity to hypoxia. However, it is associated with reduced maximal workload achieved during effort and increased chemosensitivity to hypercapnia, inducing a reduction in the ventilatory efficiency.

• Authors: Marianna Fontana, Michele Emdin, Alberto Giannoni, Giovanni Iudice, Resham Baruah, Claudio Passino
• Journal: The American journal of cardiology (Am J Cardiol) Vol. 107 Issue 11 Pg. 1675-80 (Jun 01 2011) ISSN: 1879-1913 [Electronic] United States
• PMID: 21420051 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Carbonic Anhydrase Inhibitors
• Acetazolamide

Topics

• Acetazolamide (pharmacology)
• Aged
• Carbonic Anhydrase Inhibitors (pharmacology)
• Cheyne-Stokes Respiration (drug therapy)
• Female
• Heart Failure (drug therapy)
• Humans
• Hypercapnia (drug therapy)
• Male
• Middle Aged
• Treatment Outcome