Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans

• Published in: PloS one 2016-01, Vol.11 (1), p.e0146087
• Main Authors: Basaran, Kemal Erdem, Villongco, Michael, Ho, Baran, Ellis, Erika, Zarndt, Rachel, Antonova, Julie, Hopkins, Susan R, Powell, Frank L
• Format: Article
• Language: English
• Subjects: Acclimatization; Acclimatization - drug effects; Adolescent; Adult; Altitude; Altitude effects; Animal models; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Brain stem; Breathing; Carotid body; Carotid Body - drug effects; Carotid Body - physiopathology; Chemoreceptor Cells - drug effects; Chemoreceptors; Chemoreceptors (internal); Chronic Disease; Cross-Over Studies; Dosage and administration; Double-Blind Method; Female; Gene expression; High altitude; High-altitude environments; Humans; Hypoventilation; Hypoxemia; Hypoxia; Hypoxia (Aquatic ecology); Hypoxia - physiopathology; Ibuprofen; Ibuprofen - adverse effects; Ibuprofen - pharmacology; Inflammation; Lung diseases; Male; Measurement methods; Medicine; Neural plasticity; Neuronal Plasticity - drug effects; Neuroplasticity; Nonsteroidal anti-inflammatory drugs; Oxygen - blood; Pain; Partial Pressure; Physiology; Respiration - drug effects; Respiratory Center - drug effects; Respiratory Center - physiopathology; Rodents; Sea level; Signaling; Ventilation; Ventilatory behavior; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146087

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.