Molecular oxygen (O) is a vital element in human survival and plays a major role in a diverse range of biological and physiological processes. Although normobaric hyperoxia can increase arterial oxygen content ([Formula: see text]), it also causes vasoconstriction and hence reduces O delivery in various vascular beds, including the heart, skeletal muscle, and brain. Thus, a seemingly paradoxical situation exists in which the administration of oxygen may place tissues at increased risk of hypoxic stress. Nevertheless, with various degrees of effectiveness, and not without consequences, supplemental oxygen is used clinically in an attempt to correct tissue hypoxia (e.g., brain ischemia, traumatic brain injury, carbon monoxide poisoning, etc.) and chronic hypoxemia (e.g., severe COPD, etc.) and to help with wound healing, necrosis, or reperfusion injuries (e.g., compromised grafts). Hyperoxia has also been used liberally by athletes in a belief that it offers performance-enhancing benefits; such benefits also extend to hypoxemic patients both at rest and during rehabilitation. This review aims to provide a comprehensive overview of the effects of hyperoxia in humans from the "bench to bedside." The first section will focus on the basic physiological principles of partial pressure of arterial O, [Formula: see text], and barometric pressure and how these changes lead to variation in regional O delivery. This review provides an overview of the evidence for and against the use of hyperoxia as an aid to enhance physical performance. The final section addresses pathophysiological concepts, clinical studies, and implications for therapy. The potential of O toxicity and future research directions are also considered.

Relative to 37 °C, ICE ingestion caused disproportionately greater reductions in Esk relative to Hfluid, resulting in a lower HLnet and greater S. Mechanistically, LSR and possibly SkBF were suppressed independently of Tre or Tsk, reaffirming the concept of human abdominal thermoreception. From a heat balance perspective, recommendations for ICE ingestion during exercise in warm, dry conditions should be reconsidered.

A greater ωmax occurred after 8 wk of aerobic training, but ωmax was further augmented with heat acclimation, indicating only a partially increased heat loss capacity with training. These ωmax values may assist future predictions of heat stress risk in untrained/trained unacclimated individuals and trained heat-acclimated individuals.

We sought to determine 1) the influence of adiposity on thermoregulatory responses independently of the confounding biophysical factors of body mass and metabolic heat production (Hprod); and 2) whether differences in adiposity should be accounted for by prescribing an exercise intensity eliciting a fixed Hprod per kilogram of lean body mass (LBM). Nine low (LO-BF) and nine high (HI-BF) body fat males matched in pairs for total body mass (TBM; LO-BF: 88.7 ± 8.4 kg, HI-BF: 90.1 ± 7.9 kg; P = 0.72), but with distinctly different percentage body fat (%BF; LO-BF: 10.8 ± 3.6%; HI-BF: 32.0 ± 5.6%; P < 0.001), cycled for 60 min at 28.1 ± 0.2 °C, 26 ± 8% relative humidity (RH), at a target Hprod of 1) 550 W (FHP trial) and 2) 7.5 W/kg LBM (LBM trial). Changes in rectal temperature (ΔTre) and local sweat rate (LSR) were measured continuously while whole body sweat loss (WBSL) and net heat loss (Hloss) were estimated over 60 min. In the FHP trial, ΔTre (LO-BF: 0.66 ± 0.21 °C, HI-BF: 0.87 ± 0.18 °C; P = 0.02) was greater in HI-BF, whereas mean LSR (LO-BF 0.52 ± 0.19, HI-BF 0.43 ± 0.15 mg·cm(-2)·min(-1); P = 0.19), WBSL (LO-BF 586 ± 82 ml, HI-BF 559 ± 75 ml; P = 0.47) and Hloss (LO-BF 1,867 ± 208 kJ, HI-BF 1,826 ± 224 kJ; P = 0.69) were all similar. In the LBM trial, ΔTre (LO-BF 0.82 ± 0.18 °C, HI-BF 0.54 ± 0.19 °C; P < 0.001), mean LSR (LO-BF 0.59 ± 0.20, HI-BF 0.38 ± 0.12 mg·cm(-2)·min(-1); P = 0.04), WBSL (LO-BF 580 ± 106 ml, HI-BF 381 ± 68 ml; P < 0.001), and Hloss (LO-BF 1,884 ± 277 kJ, HI-BF 1,341 ± 184 kJ; P < 0.001) were all greater at end-exercise in LO-BF. In conclusion, high %BF individuals demonstrate a greater ΔTre independently of differences in mass and Hprod, possibly due to a lower mean specific heat capacity or impaired sudomotor control. However, thermoregulatory responses of groups with different adiposity levels should not be compared using a fixed Hprod in watts per kilogram lean body mass.

Brachial artery (BA) shear-mediated dilatation is a widely used assessment of vascular function with links to coronary artery health and cardiovascular risk. r Cerebral vascular health is often interrogated using cerebrovascular (middle cerebral artery velocity) reactivity to carbon dioxide. r We show that endothelium-dependent diameter (dilator) responses are not significantly related between the internal carotid artery (ICA) and BA; nor are endothelium-independent responses. r Additionally, ICA endothelium-dependent responses are not related to middle cerebral artery velocity or ICA blood flow reactivity responses to carbon dioxide. r Therefore, assessment of large extracranial cerebral artery vascular health should be quantified via methods specific to the vessel, not via peripheral endothelial function or cerebrovascular reactivity to carbon dioxide.

Ascent to high-altitude elicits compensatory physiological adaptations in order to improve oxygenation throughout the body. The brain is particularly vulnerable to the hypoxemia of terrestrial altitude exposure. Herein we review the ventilatory and cerebrovascular changes at altitude and how they are both implicated in the maintenance of oxygen delivery to the brain. Further, the interdependence of ventilation and cerebral blood flow at altitude is discussed. Following the acute hypoxic ventilatory response, acclimatization leads to progressive increases in ventilation, and a partial mitigation of hypoxemia. Simultaneously, cerebral blood flow increases during initial exposure to altitude when hypoxemia is the greatest. Following ventilatory acclimatization to altitude, and an increase in hemoglobin concentration-which both underscore improvements in arterial oxygen content over time at altitude-cerebral blood flow progressively decreases back to sea-level values. The complimentary nature of these responses (ventilatory, hematological and cerebral) lead to a tightly maintained cerebral oxygen delivery while at altitude. Despite this general maintenance of global cerebral oxygen delivery, the manner in which this occurs reflects integration of these physiological responses. Indeed, ventilation directly influences cerebral blood flow by determining the prevailing blood gas and acid/base stimuli at altitude, but cerebral blood flow may also influence ventilation by altering central chemoreceptor stimulation via central CO washout. The causes and consequences of the integration of ventilatory and cerebral blood flow regulation at high altitude are outlined.

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.

Cardiovascular diseases (CVD) are highly prevalent in spinal cord injury (SCI), and peripheral vascular dysfunction might be a contributing factor. Recent evidence demonstrates that exposure to heat stress can improve vascular function and reduce the risk of CVD in uninjured populations. We therefore aimed to examine the extent of vascular dysfunction in SCI and the acute effects of passive heating. Fifteen participants with cervical SCI and 15 uninjured control (CON) participants underwent ultrasound assessments of vascular function and venous blood sampling for biomarkers of endothelial activation (i.e., CD62e+) and apoptosis (i.e., CD31+/42b−) before and after a 60-min exposure to lower limb hot water immersion (40°C). In SCI, macrovascular endothelial function was reduced in the brachial artery [SCI: 4.8 (3.2)% vs. CON: 7.6 (3.4)%, P = 0.04] but not the femoral artery [SCI: 3.7 (2.6)% vs. CON: 4.0 (2.1)%, P = 0.70]. Microvascular function, via reactive hyperemia, was ~40% lower in SCI versus CON in both the femoral and brachial arteries ( P < 0.01). Circulating concentrations of CD62e+ were elevated in SCI versus CON [SCI: 152 (106) microparticles/µl vs. CON: 58 (24) microparticles/µl, P < 0.05]. In response to heating, macrovascular and microvascular function remained unchanged, whereas increases (+83%) and decreases (−93%) in antegrade and retrograde shear rates, respectively, were associated with heat-induced reductions of CD62e+ concentrations in SCI to levels similar to CON ( P = 0.05). These data highlight the potential of acute heating to provide a safe and practical strategy to improve vascular function in SCI. The chronic effects of controlled heating warrant long-term testing. NEW & NOTEWORTHY Individuals with cervical level spinal cord injury exhibit selectively lower flow-mediated dilation in the brachial but not femoral artery, whereas peak reactive hyperemia was lower in both arteries compared with uninjured controls. After 60 min of lower limb hot water immersion, femoral artery blood flow and shear patterns were acutely improved in both groups. Elevated biomarkers of endothelial activation in the spinal cord injury group decreased with heating, but these biomarkers remained unchanged in controls.