title: Acetazolamide and inhaled carbon dioxide reduce periodic breathing during exercise in patients with chronic heart failure.
abstract: 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.
  
  
  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.
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Apostolo
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. Electronic address: piergiuseppe.agostoni@unimi.it.
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Agostoni
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Contini
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Antonioli
authors.affiliation: Pulmonary and Critical Care Medicine, Veterans Administration Puget Sound Health Care System, University of Washington, Seattle, Washington.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Swenson
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002245:Carbon Dioxide / Q000008:administration & dosage*; D004232:Diuretics / Q000008:administration & dosage; D005080:Exercise Test / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D011379:Prognosis; D012119:Respiration / Q000187:drug effects*; D012890:Sleep / Q000502:physiology*; D055815:Young Adult
chemical_list: D004232:Diuretics; D002245:Carbon Dioxide; D000086:Acetazolamide
keywords: Oscillatory ventilation; cardiopulmonary exercise test; polysomnography