title: AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent.
abstract: An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America; Department of Biology, University of Colorado Colorado Springs, Colorado Springs, Colorado, United States of America.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Subudhi
authors.affiliation: Institute of Sports Sciences and Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bourdillon
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Jenna
authors.initials: J
authors.lastname: Bucher
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Davis
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Elliott
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Morgan
authors.initials: M
authors.lastname: Eutermoster
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Oghenero
authors.initials: O
authors.lastname: Evero
authors.affiliation: Institute of Sports Sciences and Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland; Lemanic Doctoral School of Neuroscience, University of Lausanne, Lausanne, Switzerland.
authors.forename: Jui-Lin
authors.initials: JL
authors.lastname: Fan
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Sonja
authors.initials: S
authors.lastname: Jameson-Van Houten
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Colleen G
authors.initials: CG
authors.lastname: Julian
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kark
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Sherri
authors.initials: S
authors.lastname: Kark
authors.affiliation: Institute of Sports Sciences and Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Bengt
authors.initials: B
authors.lastname: Kayser
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Julia P
authors.initials: JP
authors.lastname: Kern
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: See Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: AnthroTronix, Inc., Silver Spring, Maryland, United States of America.
authors.forename: Corinna
authors.initials: C
authors.lastname: Lathan
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Laurie
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Lovering
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Paterson
authors.affiliation: Departments of Anesthesiology and Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Polaner
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States of America.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Ryan
authors.affiliation: United States Department of Veterans Affairs, National Center for PTSD, Pacific Islands Health Care System, and Department of Psychiatry, University of Hawaii John A. Burns School of Medicine, Honolulu, Hawaii, United States of America.
authors.forename: James L
authors.initials: JL
authors.lastname: Spira
authors.affiliation: Wounded, Ill & Injured Directorate (M9), United States Navy Bureau of Medicine and Surgery, Falls Church, Virginia, United States of America.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Tsao
authors.affiliation: Department of Sports Medicine/Sports Physiology, University of Bayreuth, Bayreuth, Germany.
authors.forename: Nadine B
authors.initials: NB
authors.lastname: Wachsmuth
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Roach
mesh_terms: D000064:Acclimatization / Q000502:physiology*; D000531:Altitude; D000532:Altitude Sickness / Q000503:physiopathology*; D001784:Blood Gas Analysis; D003071:Cognition / Q000502:physiology; D005080:Exercise Test; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000097:blood; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D010100:Oxygen