The Contribution of Arterial Blood Gases in Cerebral Blood Flow Regulation and Fuel Utilization in Man at High Altitude

Willie, Christopher K.; MacLeod, David B.; Smith, Kurt J.; Lewis, Nia C. S.; Foster, Glen E.; Ikeda, Keita; Hoiland, Ryan L.; Ainslie, Philip N.

doi:10.1038/jcbfm.2015.4

Cited by 45 publications

(67 citation statements)

References 44 publications

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“…; Willie et al . ). This is largely explained by the combined effects of reduced hydrogen buffering capacity and increased cerebral perfusion pressure (Fan et al .…”

Section: Discussionmentioning

confidence: 97%

Global REACH 2018: The influence of acute and chronic hypoxia on cerebral haemodynamics and related functional outcomes during cold and heat stress

Gibbons

Tymko

Thomas

et al. 2020

The Journal of Physiology

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Key points Thermal and hypoxic stress commonly coexist in environmental, occupational and clinical settings, yet how the brain tolerates these multi‐stressor environments is unknown Core cooling by 1.0°C reduced cerebral blood flow (CBF) by 20–30% and cerebral oxygen delivery (CDO2) by 12–19% at sea level and high altitude, whereas core heating by 1.5°C did not reliably reduce CBF or CDO2 Oxygen content in arterial blood was fully restored with acclimatisation to 4330 m, but concurrent cold stress reduced CBF and CDO2 Gross indices of cognition were not impaired by any combination of thermal and hypoxic stress despite large reductions in CDO2 Chronic hypoxia renders the brain susceptible to large reductions in oxygen delivery with concurrent cold stress, which might make monitoring core temperature more important in this context Abstract Real‐world settings are composed of multiple environmental stressors, yet the majority of research in environmental physiology investigates these stressors in isolation. The brain is central in both behavioural and physiological responses to threatening stimuli and, given its tight metabolic and haemodynamic requirements, is particularly susceptible to environmental stress. We measured cerebral blood flow (CBF, duplex ultrasound), cerebral oxygen delivery (CDO2), oesophageal temperature, and arterial blood gases during exposure to three commonly experienced environmental stressors – heat, cold and hypoxia – in isolation, and in combination. Twelve healthy male subjects (27 ± 11 years) underwent core cooling by 1.0°C and core heating by 1.5°C in randomised order at sea level; acute hypoxia (PET,O2 = 50 mm Hg) was imposed at baseline and at each thermal extreme. Core cooling and heating protocols were repeated after 16 ± 4 days residing at 4330 m to investigate any interactions with high altitude acclimatisation. Cold stress decreased CBF by 20–30% and CDO2 by 12–19% (both P < 0.01) irrespective of altitude, whereas heating did not reliably change either CBF or CDO2 (both P > 0.08). The increases in CBF with acute hypoxia during thermal stress were appropriate to maintain CDO2 at normothermic, normoxic values. Reaction time was faster and slower by 6–9% with heating and cooling, respectively (both P < 0.01), but central (brain) processes were not impaired by any combination of environmental stressors. These findings highlight the powerful influence of core cooling in reducing CDO2. Despite these large reductions in CDO2 with cold stress, gross indices of cognition remained stable.

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“…; Willie et al . ). This is largely explained by the combined effects of reduced hydrogen buffering capacity and increased cerebral perfusion pressure (Fan et al .…”

Section: Discussionmentioning

confidence: 97%

Global REACH 2018: The influence of acute and chronic hypoxia on cerebral haemodynamics and related functional outcomes during cold and heat stress

Gibbons

Tymko

Thomas

et al. 2020

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…, Willie et al . ). At present, the cause of this discrepancy is unclear, although at least three explanations are conceivable.…”

Section: Discussionmentioning

confidence: 97%

“…; Willie et al . ) and with acclimatization to hypoxia, make these observations difficult to explain (Möller et al . ).…”

Section: Discussionmentioning

confidence: 99%

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Unexpected reductions in regional cerebral perfusion during prolonged hypoxia

Lawley

Macdonald

Oliver

et al. 2016

The Journal of Physiology

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Hypoxia causes an increase in global cerebral blood flow, which maintains global cerebral oxygen delivery and metabolism. However, neurological deficits are abundant under hypoxic conditions. We investigated regional cerebral microvascular responses to acute (2 h) and prolonged (10 h) poikilocapnic normobaric hypoxia. We found that 2 h of hypoxia caused an expected increase in frontal cortical grey matter perfusion but unexpected perfusion decreases in regions of the brain normally associated with the 'default mode' or 'task negative' network. After 10 h in hypoxia, decreased blood flow to the major nodes of the default mode network became more pronounced and widespread. The use of a hypercapnic challenge (5% CO ) confirmed that these reductions in cerebral blood flow from hypoxia were related to vasoconstriction. Our findings demonstrate steady-state deactivation of the default network under acute hypoxia, which become more pronounced over time. Moreover, these data provide a unique insight into the nuanced localized cerebrovascular response to hypoxia that is not attainable through traditional methods. The observation of reduced perfusion in the posterior cingulate and cuneal cortex, which are regions assumed to play a role in declarative and procedural memory, provides an anatomical mechanism through which hypoxia may cause deficits in working memory.

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“…This study was part of a larger research expedition conducted in April-June 2012 Lewis et al 2014;Smirl et al 2014;Smith et al 2014;Willie et al 2014Willie et al , 2015Stembridge et al 2015). All participants provided written informed consent before participation in this study.…”

Section: Methodsmentioning

confidence: 99%

Reduced blood flow through intrapulmonary arteriovenous anastomoses during exercise in lowlanders acclimatizing to high altitude

Boulet

Lovering

Tymko

et al. 2017

Experimental Physiology

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What is the central question of this study? The aim was to determine, using the technique of agitated saline contrast echocardiography, whether exercise after 4-7 days at 5050 m would affect blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) compared with exercise at sea level. What is the main finding and its importance? Despite a significant increase in both cardiac output and pulmonary pressure during exercise at high altitude, there is very little Q̇IPAVA at rest or during exercise after 4-7 days of acclimatization. Mathematical modelling suggests that bubble instability at high altitude is an unlikely explanation for the reduced Q̇IPAVA. Blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) is elevated during exercise at sea level (SL) and at rest in acute normobaric hypoxia. After high altitude (HA) acclimatization, resting Q̇IPAVA is similar to that at SL, but it is unknown whether this is true during exercise at HA. We reasoned that exercise at HA (5050 m) would exacerbate Q̇IPAVA as a result of heightened pulmonary arterial pressure. Using a supine cycle ergometer, seven healthy adults free from intracardiac shunts underwent an incremental exercise test at SL [25, 50 and 75% of SL peak oxygen consumption (V̇O2 peak )] and at HA (25 and 50% of SL V̇O2 peak ). Echocardiography was used to determine cardiac output (Q̇) and pulmonary artery systolic pressure (PASP), and agitated saline contrast was used to determine Q̇IPAVA (bubble score; 0-5). The principal findings were as follows: (i) Q̇ was similar at SL rest (3.9 ± 0.47 l min ) compared with HA rest (4.5 ± 0.49 l min ; P = 0.382), but increased from rest during both SL and HA exercise (P < 0.001); (ii) PASP increased from SL rest (19.2 ± 0.7 mmHg) to HA rest (33.7 ± 2.8 mmHg; P = 0.001) and, compared with SL, PASP was further elevated during HA exercise (P = 0.003); (iii) Q̇IPAVA was increased from SL rest (0) to HA rest (median = 1; P = 0.04) and increased from resting values during SL exercise (P < 0.05), but was unchanged during HA exercise (P = 0.91), despite significant increases in Q̇ and PASP. Theoretical modelling of microbubble dissolution suggests that the lack of Q̇IPAVA in response to exercise at HA is unlikely to be caused by saline contrast instability.

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The Contribution of Arterial Blood Gases in Cerebral Blood Flow Regulation and Fuel Utilization in Man at High Altitude

Cited by 45 publications

References 44 publications

Global REACH 2018: The influence of acute and chronic hypoxia on cerebral haemodynamics and related functional outcomes during cold and heat stress

Global REACH 2018: The influence of acute and chronic hypoxia on cerebral haemodynamics and related functional outcomes during cold and heat stress

Unexpected reductions in regional cerebral perfusion during prolonged hypoxia

Reduced blood flow through intrapulmonary arteriovenous anastomoses during exercise in lowlanders acclimatizing to high altitude

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