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Original Research: Sleep Disorders |

Sex and Acetazolamide Effects on Chemoreflex and Periodic Breathing During Sleep at AltitudeSex, Acetazolamide and Breathing at Altitude

Sergio Caravita, MD; Andrea Faini, PhD; Carolina Lombardi, MD, PhD; Mariaconsuelo Valentini, MD; Francesca Gregorini, MSc; Jessica Rossi, MD; Paolo Meriggi, PhD; Marco Di Rienzo, MSc; Grzegorz Bilo, MD, PhD; Piergiuseppe Agostoni, MD, PhD; Gianfranco Parati, MD, PhD
Author and Funding Information

From Istituto Auxologico Italiano (Drs Caravita, Faini, Lombardi, Valentini, Rossi, Bilo, and Parati and Ms Gregorini), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Department of Cardiovascular, Neural and Metabolic Sciences, S. Luca Hospital; the Department of Health Sciences (Drs Caravita and Parati), University of Milano-Bicocca; Polo Tecnologico (Dr Meriggi and Mr Di Rienzo), Biomedical Technology Department, Fondazione Don Carlo Gnocchi Onlus; Centro Cardiologico Monzino (Dr Agostoni), IRCCS; and the Department of Clinical Sciences and Community Health (Dr Agostoni), University of Milan, Milan, Italy.

CORRESPONDENCE TO: Gianfranco Parati, MD, PhD, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico, Department of Cardiovascular, Neural and Metabolic Sciences, S. Luca Hospital, Piazzale Brescia 20, 20149 Milan, Italy; e-mail: gianfranco.parati@unimib.it


Drs Caravita, Faini, and Lombardi contributed equally to this manuscript.

Part of this article has been presented in abstract form (Lombardi C, Faini A, Meriggi P, et al. Acetazolamide effect on high altitude periodic breathing during sleep. The HIGHCARE Alps project. Eur Heart J. 2013;34(S1):312) and presented at the European Society of Cardiology Congress, August 31–September 4, 2013, Amsterdam, The Netherlands.

FUNDING/SUPPORT: This study was supported primarily by a research grant from the Italian Ministry of Health. Supplementary financial support was provided by the IRCCS Istituto Auxologico Italiano, Milan, Italy. Tao Med provided the metabolic chart for high altitude recordings.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(1):120-131. doi:10.1378/chest.14-0317
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OBJECTIVE:  Nocturnal periodic breathing occurs more frequently in men than in women with various clinical and pathophysiologic conditions. The mechanisms accounting for this sex-related difference are not completely understood. Acetazolamide effectively counteracts nocturnal periodic breathing, but it has been investigated almost exclusively in men. Our aim was to explore possible determinants of nocturnal periodic breathing in a high-altitude setting both in men and in women. We hypothesized that increased hypoxic chemosensitivity in men could be associated with the development of nocturnal periodic breathing at altitude more frequently than in women, and that acetazolamide, by leftward shifting the CO2 ventilatory response, could improve nocturnal periodic breathing at altitude in a sex-independent manner.

METHODS:  Forty-four healthy lowlanders (21 women), randomized to acetazolamide or placebo, underwent cardiorespiratory sleep studies at sea level off treatment and under treatment on the first night after arrival at a 4,559-m altitude. Hypoxic and hypercapnic chemosensitivities were assessed at sea level.

RESULTS:  Men, more frequently than women, exhibited increased hypoxic chemosensitivity and displayed nocturnal periodic breathing at altitude. Acetazolamide leftward shifted the CO2 set point and, at altitude, improved oxygenation and reduced periodic breathing in both sexes, but to a larger extent in men. Hypoxic chemosensitivity directly correlated with the number of apneas/hypopneas at altitude in the placebo group but not in the acetazolamide group.

CONCLUSIONS:  The greater severity of periodic breathing during sleep displayed by men at altitude could be attributed to their increased hypoxic chemosensitivity. Acetazolamide counteracted the occurrence of periodic breathing at altitude in both sexes, modifying the apneic threshold and improving oxygenation.

TRIAL REGISTRY:  EU Clinical Trials Register, EudraCT; No.: 2010-019986-27; URL: https://www.clinicaltrialsregister.eu

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