title: Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans.
abstract: Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400 mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease.
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, San Diego, California, United States of America.|Department of Medical Physiology, Faculty of Medicine, Erciyes University, Melikgazi, Kayseri, Turkey.
authors.forename: Kemal Erdem
authors.initials: KE
authors.lastname: Basaran
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Villongco
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Baran
authors.initials: B
authors.lastname: Ho
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Erika
authors.initials: E
authors.lastname: Ellis
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Zarndt
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Antonova
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, San Diego, California, United States of America.|Department of Radiology, University of California San Diego, San Diego, California, United States of America.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Hopkins
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Powell
mesh_terms: D000064:Acclimatization / Q000187:drug effects*; D000293:Adolescent; D000328:Adult; D000531:Altitude; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D002344:Carotid Body / Q000187:drug effects* / Q000503:physiopathology; D002628:Chemoreceptor Cells / Q000187:drug effects*; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007052:Ibuprofen / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D012119:Respiration / Q000187:drug effects*; D012125:Respiratory Center / Q000187:drug effects* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010100:Oxygen; D007052:Ibuprofen