title: Hypercapnia is essential to reduce the cerebral oxidative metabolism during extreme apnea in humans.
abstract: The cerebral metabolic rate of oxygen (CMRO2) is reduced during apnea that yields profound hypoxia and hypercapnia. In this study, to dissociate the impact of hypoxia and hypercapnia on the reduction in CMRO2, 11 breath-hold competitors completed three apneas under: (a) normal conditions (NM), yielding severe hypercapnia and hypoxemia, (b) with prior hyperventilation (HV), yielding severe hypoxemia only, and (c) with prior 100% oxygen breathing (HX), yielding the greatest level of hypercapnia, but in the absence of hypoxemia. The CMRO2was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-jugular venous oxygen content difference (cannulation). Secondary measures included net-cerebral glucose/lactate exchange and nonoxidative metabolism. Reductions in CMRO2were largest in the HX condition (-44 ± 15%, p < 0.05), with the most severe hypercapnia (PaCO2= 58 ± 5 mmHg) but maintained oxygen saturation. The CMRO2was reduced by 24 ± 27% in NM ( p = 0.05), but unchanged in the HV apnea where hypercapnia was absent. A net-cerebral lactate release was observed at the end of apnea in the HV and NM condition, but not in the HX apnea (main effect p < 0.05). These novel data support hypercapnia/pH as a key mechanism mediating reductions in CMRO2during apnea, and show that severe hypoxemia stimulates lactate release from the brain.
authors.affiliation: 1 Centre for Heart Lung and Vascular Health, University of British Columbia, Kelowna, BC, Canada.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Bain
authors.affiliation: 1 Centre for Heart Lung and Vascular Health, University of British Columbia, Kelowna, BC, Canada.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ainslie
authors.affiliation: 2 School of Medicine, University of Split, Split, Croatia.
authors.forename: Otto F
authors.initials: OF
authors.lastname: Barak
authors.affiliation: 3 Faculty of Medicine, University of Novi Sad, Serbia.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Hoiland
authors.affiliation: 4 School of Kinesiology, University of Zagreb, Zagreb, Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Drvis
authors.affiliation: 2 School of Medicine, University of Split, Split, Croatia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Mijacika
authors.affiliation: 5 Faculty of Life Sciences and Education, University of South Wales, Glamorgan, UK.
authors.forename: Damian M
authors.initials: DM
authors.lastname: Bailey
authors.affiliation: 6 Duke University Medical Center, Durham, NC, USA.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Santoro
authors.affiliation: 6 Duke University Medical Center, Durham, NC, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: DeMasi
authors.affiliation: 2 School of Medicine, University of Split, Split, Croatia.
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Dujic
authors.affiliation: 6 Duke University Medical Center, Durham, NC, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: MacLeod
mesh_terms: D000328:Adult; D001049:Apnea / Q000378:metabolism* / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000502:physiology; D062485:Breath Holding; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D007601:Jugular Veins; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood
chemical_list: D019344:Lactic Acid; D010100:Oxygen
keywords: Hypoxia; brain metabolism; breath-holding; cerebral lactate release; cerebral nonoxidative metabolism