Acetazolamide and inhaled carbon dioxide reduce periodic breathing during exercise in patients with chronic heart failure.
BACKGROUND
Periodic breathing (PB) during sleep and exercise in heart failure (HF) is related to respiratory acid-base status, CO2 chemosensitivity, and temporal dynamics of CO2 and O2 sensing. We studied inhaled CO2 and acetazolamide to alter these factors and reduce PB.


METHODS AND RESULTS
We measured expired and arterial gases and PB amplitude and duration in 20 HF patients during exercise before and after acetazolamide given acutely (500 mg intravenously) and prolonged (24 hours, 2 g orally), and we performed overnight polysomnography. We studied CO2 inhalation (1%-2%) during constant workload exercise. PB disappeared in 19/20 and 2/7 patients during 2% and 1% CO2. No changes in cardiorespiratory parameters were observed after acute acetazolamide. With prolonged acetazolamide at rest: ventilation +2.04 ± 4.0 L/min (P = .001), tidal volume +0.11 ± 1.13 L (P = .003), respiratory rate +1.24 ± 4.63 breaths/min (NS), end-tidal PO2 +4.62 ± 2.43 mm Hg (P = .001), and end-tidal PCO2 -2.59 ± 9.7 mm Hg (P < .001). At maximum exercise: Watts -10% (P < .02), VO2 -61 ± 109 mL/min (P = .04) and VCO2 101 ± 151 mL/min (P < .02). Among 20 patients, PB disappeared in 1 and 7 subjects after acute and prolonged acetazolamide, respectively. PB was present 80% ± 26, 65% ± 28, and 43% ± 39 of exercise time before and after acute and prolonged acetazolamide, respectively. Overnight apnea/hypopnea index decreased from 30.8 ± 83.8 to 21.1 ± 16.9 (P = .003).


CONCLUSIONS
In HF, inhaled CO2 and acetazolamide reduce exercise PB with additional benefits of acetazolamide on sleep PB.