Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m

Brain blood flow increases during the first week of living at high altitude. We do not understand completely what causes the increase or how the factors that regulate brain blood flow are affected by the high‐altitude environment. Our results show that the balance of oxygen (O2) and carbon dioxide (CO2) pressures in arterial blood explains 40% of the change in brain blood flow upon arrival at high altitude (5050 m). We also show that blood vessels in the brain respond to increases and decreases in CO2 differently at high altitude compared to sea level, and that this can affect breathing responses as well. These results help us to better understand the regulation of brain blood flow at high altitude and are also relevant to diseases that are accompanied by reductions in the pressure of oxygen in the blood.

[1]  N. Toda,et al.  Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances , 2009, Pharmacological Reviews.

[2]  P Richards,et al.  High Altitude Illness , 2011, Journal of the Royal Army Medical Corps.

[3]  L. Celi,et al.  Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation: alterations with hyperoxia. , 2008, Journal of applied physiology.

[4]  P. Ainslie,et al.  Alterations in cerebral dynamics at high altitude following partial acclimatization in humans: wakefulness and sleep. , 2007, Journal of applied physiology.

[5]  C B Wolff,et al.  Cerebral blood flow and oxygen delivery at high altitude. , 2000, High altitude medicine & biology.

[6]  J. Calbet Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans , 2003, The Journal of physiology.

[7]  J. Severinghaus,et al.  Respiratory insensitivity to hypoxia in chronically hypoxic man. , 1966, Respiration physiology.

[8]  Philip N. Ainslie,et al.  Cardiorespiratory and cerebrovascular responses to hyperoxic and hypoxic rebreathing: Effects of acclimatization to high altitude , 2008, Respiratory Physiology & Neurobiology.

[9]  Rong Zhang,et al.  Transcranial Doppler estimation of cerebral blood flow and cerebrovascular conductance during modified rebreathing. , 2007, Journal of applied physiology.

[10]  P. Ainslie,et al.  Influence of indomethacin on ventilatory and cerebrovascular responsiveness to CO2 and breathing stability: the influence of PCO2 gradients. , 2010, American journal of physiology. Regulatory, integrative and comparative physiology.

[11]  Olaf B. Paulson,et al.  Unchanged Cerebral Blood Flow and Oxidative Metabolism after Acclimatization to High Altitude , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  P. Ainslie,et al.  Cardiorespiratory and cerebrovascular responses to acute poikilocapnic hypoxia following intermittent and continuous exposure to hypoxia in humans. , 2007, Journal of applied physiology.

[13]  T. Hornbein,et al.  Cerebral Circulation at High Altitude , 2001 .

[14]  P. Ainslie,et al.  Exacerbation of obstructive sleep apnea by oral indomethacin. , 2010, Chest.

[15]  Kojiro Ide,et al.  Relationship between middle cerebral artery blood velocity and end-tidal PCO2 in the hypocapnic-hypercapnic range in humans. , 2003, Journal of applied physiology.

[16]  N. Laird,et al.  Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. , 1997, Statistics in medicine.

[17]  B. Townes,et al.  The cost to the central nervous system of climbing to extremely high altitude. , 1989, The New England journal of medicine.

[18]  E. Skinhøj,et al.  Cerebral blood-flow. , 1972 .

[19]  B. Basnyat,et al.  Cerebral vasomotor reactivity at high altitude in humans. , 1999, Journal of applied physiology.

[20]  Charles S. Houston,et al.  THE LAKE-LOUISE ACUTE MOUNTAIN-SICKNESS SCORING SYSTEM , 1993 .

[21]  C. Lundby,et al.  Transcerebral Exchange Kinetics of Nitrite and Calcitonin Gene-Related Peptide in Acute Mountain Sickness: Evidence Against Trigeminovascular Activation? , 2009, Stroke.

[22]  D J Reis,et al.  Neurons of a Limited Subthalamic Area Mediate Elevations in Cortical Cerebral Blood Flow Evoked by Hypoxia and Excitation of Neurons of the Rostral Ventrolateral Medulla , 2001, The Journal of Neuroscience.

[23]  Thomas F. Hornbein,et al.  Cerebral Blood Flow In Man at High Altitude: Role of Cerebrospinal Fluid pH in Normalization of Flow in Chronic Hypocapnia , 1966, Circulation research.

[24]  B. Levine,et al.  Impaired Dynamic Cerebral Autoregulation at Extreme High Altitude Even after Acclimatization , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  A. Ngai,et al.  Changes in Pial Arteriolar Diameter and CSF Adenosine Concentrations during Hypoxia , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  J A Dempsey,et al.  Mediation of Ventilatory Adaptations. , 1982, Physiological reviews.

[27]  M. Rostrup Catecholamines, hypoxia and high altitude. , 1998, Acta physiologica Scandinavica.

[28]  J. Dempsey,et al.  Cerebrovascular response to carbon dioxide in patients with congestive heart failure. , 2005, American journal of respiratory and critical care medicine.

[29]  C. Ince,et al.  Role of the altitude level on cerebral autoregulation in residents at high altitude. , 2007, Journal of applied physiology.

[30]  Sujoy B. Roy,et al.  Immediate Circulatory Response to High Altitude Hypoxia in Man , 1968, Nature.

[31]  J. V. van Lieshout,et al.  Cerebral blood flow and metabolism during exercise: implications for fatigue. , 2008, Journal of applied physiology.

[32]  R. Aaslid,et al.  Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. , 1982, Journal of neurosurgery.

[33]  Shigehiko Ogoh,et al.  Regulation of cerebral blood flow in mammals during chronic hypoxia: a matter of balance , 2010, Experimental physiology.

[34]  Jean-Jacques Moraine,et al.  Effects of High Altitude Exposure on Cerebral Hemodynamics in Normal Subjects , 2005, Stroke.

[35]  E. Swenson,et al.  Acetazolamide 125 mg BD is not significantly different from 375 mg BD in the prevention of acute mountain sickness: the prophylactic acetazolamide dosage comparison for efficacy (PACE) trial. , 2006, High altitude medicine & biology.

[36]  F. Faraci,et al.  Nitric Oxide and the Cerebral Circulation , 1994, Stroke.

[37]  J T Reeves,et al.  Internal carotid and vertebral arterial flow velocity in men at high altitude. , 1987, Journal of applied physiology.

[38]  A. Delabays,et al.  Augmented sympathetic activation during short-term hypoxia and high-altitude exposure in subjects susceptible to high-altitude pulmonary edema. , 1999, Circulation.

[39]  R. Panerai,et al.  Effects of Hypobaric Hypoxia on Cerebral Autoregulation , 2010, Stroke.

[40]  K. Kallenberg,et al.  Free Radical-Mediated Damage to Barrier Function is not Associated with Altered Brain Morphology in High-Altitude Headache , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  F. Léon-Velarde,et al.  Acetazolamide: a treatment for chronic mountain sickness. , 2005, American journal of respiratory and critical care medicine.

[42]  N. Lassen,et al.  Cerebral glucose metabolism and cerebral blood flow in high-altitude residents. , 1974, Journal of applied physiology.

[43]  Bruno Chenuel,et al.  Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans , 2006, The Journal of physiology.

[44]  P. Ainslie,et al.  Initial orthostatic hypotension at high altitude. , 2010, High altitude medicine & biology.

[45]  Stanton Newman,et al.  The cerebral effects of ascent to high altitudes , 2009, The Lancet Neurology.

[46]  R L Burse,et al.  Procedures for the measurement of acute mountain sickness. , 1983, Aviation, space, and environmental medicine.

[47]  A. Blaber,et al.  Effect of acute exposure to 3660 m altitude on orthostatic responses and tolerance. , 2003, Journal of applied physiology.

[48]  S. Kety,et al.  THE EFFECTS OF ALTERED ARTERIAL TENSIONS OF CARBON DIOXIDE AND OXYGEN ON CEREBRAL BLOOD FLOW AND CEREBRAL OXYGEN CONSUMPTION OF NORMAL YOUNG MEN. , 1948, The Journal of clinical investigation.

[49]  Joseph Donnelly,et al.  Influence of cerebral blood flow on breathing stability , 2009 .

[50]  P N Ainslie,et al.  On the regulation of the blood supply to the brain: old age concepts and new age ideas. , 2010, Journal of applied physiology.

[51]  J. Skatrud,et al.  Impaired vascular regulation in patients with obstructive sleep apnea: effects of continuous positive airway pressure treatment. , 2009, American journal of respiratory and critical care medicine.

[52]  T. Mano,et al.  Responses in muscle sympathetic activity to acute hypoxia in humans. , 1988, Journal of applied physiology.

[53]  M. Reivich,et al.  Effects of hypoxia and normocarbia on cerebral blood flow and metabolism in conscious man. , 1967, Journal of applied physiology.

[54]  D J Reis,et al.  Contribution of oxygen‐sensitive neurons of the rostral ventrolateral medulla to hypoxic cerebral vasodilatation in the rat. , 1996, The Journal of physiology.

[55]  Kojiro Ide,et al.  Differential responses to CO2 and sympathetic stimulation in the cerebral and femoral circulations in humans , 2005, The Journal of physiology.

[56]  James Duffin,et al.  Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation. , 2009, American journal of physiology. Regulatory, integrative and comparative physiology.

[57]  M. Sander,et al.  Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia , 2003, The Journal of physiology.

[58]  Leo Celi,et al.  Human cerebrovascular and ventilatory CO2 reactivity to end‐tidal, arterial and internal jugular vein PCO2 , 2007, The Journal of physiology.

[59]  W. Ritschel,et al.  Pharmacokinetics of Acetazolamide in Healthy Volunteers after Short‐ and Long‐Term Exposure to High Altitude , 1996, Journal of clinical pharmacology.