High-altitude cerebral edema (HACE) and acute mountain sickness (AMS) are neuropathologies associated with rapid exposure to hypoxia. However, speculation remains regarding the exact etiology of both HACE and AMS and whether they share a common mechanistic pathology. This review outlines the basic principles of HACE development, highlighting how edema could develop from 1) a progression from cytotoxic swelling to ionic edema or 2) permeation of the blood brain barrier (BBB) with or without ionic edema. Thereafter, discussion turns to the available neuroimaging literature in the context of cytotoxic, ionic, or vasogenic edema in both HACE and AMS. Although HACE is clearly caused by an increase in brain water of ionic and/or vasogenic origin, there is very little evidence that this type of edema is present when AMS develops. However, cerebral vasodilation, increased intracranial blood volume, and concomitant intracranial fluid shifts from the extracellular to the intracellular space, as interpreted from changes in diffusion indices within white matter, are observed consistently in persons acutely exposed to hypoxia and with AMS. Therefore, herein we explore the idea that intracellular swelling occurs alongside AMS, and is a critical precursor to extracellular ionic edema formation. We propose that this process produces a subtle modulation of the BBB, which either together with or independent of vasogenic edema provides a transvascular segue from the end-stage of AMS to HACE. Ultimately, this review seeks to shed light on the possible processes underlying HACE pathophysiology, and thus highlights potential avenues for future prevention and treatment.

Although not a barrier to perform sport, cold weather environments (low ambient temperature, high wind speeds, and increased precipitation, i.e., rain/water/snow) may influence sport performance. Despite the obvious requirement for practical recommendations and guidelines to better facilitate training and competition in such cold environments, the current scientific evidence-base is lacking. Nonetheless, this review summarizes the current available knowledge specifically related to the physiological impact of cold exposure, in an attempt to provide practitioners and coaches alike with practical recommendations to minimize any potential negative performance effects, mitigate health issues, and best optimize athlete preparation across various sporting disciplines. Herein, the review is split into sections which explore some of the key physiological effects of cold exposure on performance (i.e., endurance exercise capacity and explosive athletic power), potential health issues (short-term and long-term), and what is currently known with regard to best preparation or mitigation strategies considered to negate the potential negative effects of cold on performance. Specific focus is given to “winter” sports that are usually completed in cold environments and practical recommendations for physical preparation.

Key points: Acclimatization to hypoxia leads to a reduction in plasma volume (PV) that restores arterial O₂ content. Findings from studies investigating the mechanisms underlying this PV contraction have been controversial, possibly as experimental conditions were inadequately controlled. We examined the mechanisms underlying the PV contraction evoked by 4 days of exposure to hypobaric hypoxia (HH) in 11 healthy lowlanders, while strictly controlling water intake, diet, temperature and physical activity. Exposure to HH‐induced an ∼10% PV contraction that was accompanied by a reduction in total circulating protein mass, whereas diuretic fluid loss and total body water remained unchanged. Our data support an oncotically driven fluid redistribution from the intra‐ to the extravascular space, rather than fluid loss, as the mechanism underlying HH‐induced PV contraction. Extended hypoxic exposure reduces plasma volume (PV). The mechanisms underlying this effect are controversial, possibly as previous studies have been confounded by inconsistent experimental conditions. Here, we investigated the effect of hypobaric hypoxia (HH) on PV in a cross‐over study that strictly controlled for diet, water intake, physical activity and temperature. Eleven males completed two 4‐day sojourns in a hypobaric chamber, one in normoxia (NX) and one in HH equivalent to 3500 m altitude. PV, urine output, volume‐regulating hormones and plasma protein concentration were determined daily. Total body water (TBW) was determined at the end of both sojourns by deuterium dilution. Although PV was 8.1 ± 5.8% lower in HH than in NX after 24 h and remained ∼10% lower thereafter (all P < 0.002), no differences were detected in TBW (P = 0.17) or in 24 h urine volumes (all P > 0.23). Plasma renin activity and circulating aldosterone were suppressed in HH during the first half of the sojourn (all P < 0.05) but thereafter similar to NX, whereas no differences were detected for copeptin between sojourns (all P > 0.05). Markers for atrial natriuretic peptide were higher in HH than NX after 30 min (P = 0.001) but lower during the last 2 days (P < 0.001). While plasma protein concentration was similar between sojourns, total circulating protein mass (TCP) was reduced in HH at the same time points as PV (all P < 0.03). Despite transient hormonal changes favouring increased diuresis, HH did not enhance urine output. Instead, the maintained TBW and reduced TCP support an oncotically driven fluid redistribution into the extravascular compartment as the mechanism underlying PV contraction.

Using a normoxic crossover study design, we examined the impact of hypobaric hypoxia (4 days; altitude equivalent, 3,500 m) and hemoconcentration on blood viscosity, shear stress, and endothelial function. Blood viscosity increased during the hypoxic exposure and was accompanied by elevated resting and exercising arterial shear stress. Flow-mediated dilation stimulated by reactive hyperemia and handgrip exercise was preserved throughout the hypoxic exposure. Plasma volume expansion reversed the hypoxia-associated hemoconcentration and selectively increased handgrip exercise flow-mediated dilation.

This study is the first to investigate the mechanisms underlying plasma volume (PV) contraction in response to hypoxia in women while strictly controlling for confounders. PV contraction in women has a similar time course and magnitude as in men and is driven by the same mechanism, namely, oncotically driven redistribution rather than loss of fluid. We further report that hypoxia facilitates an increase in diuresis, that is, however, short-lived and of little relevance for PV regulation.

A sufficient supply of oxygen is crucial to avoid hypoxic cardiac arrest and brain damage within 30 min in completely-buried avalanche victims. Snow density influences levels of hypoxia and hypercapnia. The goal of this study was to investigate the effects of hypoxia and hypercapnia on cerebral oxygenation (ScO2) in humans breathing into an artificial air pocket. Each subject breathed into a closed system (air-tight face mask - plastic tube - snow air-pocket of 4 L) up to 30 min. Each subject performed three tests in different snow densities. ScO2 was measured by a near-infrared spectroscopy (NIRS) device. Measurements included peripheral oxygen saturation (SpO2), end-tidal carbon dioxide (ETCO2), air pocket gases and blood gases. Snow density was assessed via standard methods and micro-computed tomography. Based on predetermined criteria, tests were classified based on whether they were terminated before 30 min and the reason for termination. The categories were: completed tests (30 min), tests terminated before 30 min when SpO2 dropped to ≤75% and tests that were terminated before 30 min by requests of the subjects. General linear models were used to compare termination groups for changes in ScO2, ETCO2, SpO2 and air pocket gases, and a multivariate analysis was used to detect factor independent effects on ScO2. ScO2 was decreased in the group in which the tests were terminated for SpO2≤75% caused by a decrease in oxygen supply in high snow densities. In the completed tests, an increase in ScO2 occurred despite decreased oxygen supply and decreased carbon dioxide removal. Our data show that ScO2 determined by NIRS was not always impaired in humans breathing into an artificial air pocket despite decreased oxygen supply and decreased carbon dioxide removal. This may indicate that in medium to low snow densities brain oxygenation can be sufficient, which may reflect the initial stage of the triple H (hypothermia, hypoxia, and hypercapnia) syndrome. In high snow densities, ScO2 showed a significant decrease caused by a critical decrease in oxygen supply. This could lead to a higher risk of hypoxic cardiac arrest and brain damage.