Joshua C. Tremblay

High‐altitude hypoxia elicits several profound physiological responses, including substantial increases in muscle sympathetic nerve activity (MSNA); however, the association of this heightened MSNA with cardiovascular and cerebrovascular haemodynamics remains unclear in lowlanders and indigenous highlander populations. We hypothesized that at high altitude resting MSNA would be associated with resting cardiovascular and cerebrovascular haemodynamics in lowlanders ( n = 26), and Sherpa ( n = 8) and Andean ( n = 23) indigenous highlanders. Data were retrospectively analysed from two separate high‐altitude expeditions to Nepal (2016; 5050 m) and Peru (2018; 4300 m). We assessed resting MSNA via radial or peroneal microneurography, and measured , heart rate, mean arterial pressure, brachial artery blood flow and endothelial function, and internal carotid and vertebral artery diameter, velocity, and blood flow. Resting MSNA demonstrated limited, population‐specific associations with vascular haemodynamics. Lowlanders showed the most consistent relationships, including positive associations between MSNA and heart rate, vertebral artery diameter and blood flow, and internal carotid artery velocity, while Sherpa and Andean highlanders showed few systemic or cerebrovascular associations with MSNA. No relationship was observed between MSNA and , brachial artery blood flow or endothelial function across populations. Sensitivity analysis confirmed that most directional relationships were robust to the removal of influential participants, although some associations, including the negative relationship between MSNA and brachial artery blood flow in Sherpa, were attenuated. These data highlight that single time‐point, resting MSNA may have limited predictive value for cardiovascular and cerebrovascular haemodynamics at high altitude within these specific populations; however, these data should be interpreted with caution, given the small cross‐sectional sample sizes.

Cardiac disease is a leading cause of death in chimpanzees (Pan troglodytes), although existing data largely derive from animals housed in zoological and research facilities. To evaluate the influence of environment on cardiac health, we compared echocardiographic measures of left ventricular (LV) structure and function in age- and sex-matched chimpanzees living in a research facility and African sanctuaries (n = 144). Chimpanzees in the research facility were heavier and exhibited significantly greater LV mass and relative wall thickness, consistent with concentric LV hypertrophy. Early mitral inflow velocities were similar between groups, whereas late mitral inflow velocities were higher in research-housed chimpanzees, suggestive of impaired diastolic function. Although differences in body mass partially explained these findings, substantial group differences persisted, suggesting that additional aspects of the captive research environment contribute to adverse LV remodelling. Across the cohort, markers of altered LV structure were associated with lower indices of diastolic function, paralleling patterns observed in humans. Overall, chimpanzees housed in research facilities exhibited structural and functional cardiac changes consistent with pathological cardiac ageing, in contrast to those living in African sanctuaries. These results highlight the importance of environmental factors in chimpanzee cardiovascular health and underscore the need for longitudinal studies to disentangle the individual and combined effects of management practices on cardiac outcomes.

Far‐infrared (FIR) saunas are increasingly used as a passive heating and ‘wellness’ modality, yet their capacity to elevate core temperature remains unclear, particularly given prior work at lower temperatures (∼45°C) reports limited net heat storage. We therefore examined whether FIR sauna exposure at an ambient temperature more typical of traditional sauna bathing (65°C) increases core (rectal) temperature and evokes thermoregulatory, cardiovascular, haematological and perceptual responses associated with heat strain. Twelve healthy adults (6 female) completed a single 45‐min FIR sauna exposure. Rectal temperature, skin temperature, heart rate, blood pressure, plasma volume changes and perceptual measures were assessed throughout. Rectal temperature increased by 1.4°C (95% CI: 0.9, 1.8; P  < 0.001), with elevations evident from ∼20 min. Skin temperature rose rapidly (+7.4°C [95% CI: 5.4, 9.5] at 5 min; P  < 0.001) and remained elevated thereafter. Heart rate increased from 74 ± 15 to 153 ± 20 bpm ( P  < 0.001), while mean arterial pressure decreased immediately post‐exposure (−9 mmHg [95% CI: −2, −16]; P  = 0.012), driven by reductions in diastolic pressure. Plasma volume contracted by −11.6% (95% CI: −15.9, −7.2; P  < 0.001), with a sweat rate of 1.4 ± 0.5 L h ^{− 1} . Thermal sensation and discomfort increased to ‘extremely hot’ and ‘extremely uncomfortable’, respectively ( P  < 0.001). In summary, FIR sauna exposure at 65°C elicits substantial increases in rectal temperature and systemic physiological strain comparable to values previously reported in the passive heating literature. These findings indicate that the effectiveness of FIR sauna to increase core temperature is governed by the thermal load imposed, supporting its potential as a heat‐based intervention when applied at sufficiently high temperatures.

High‐altitude exposure increases haemoglobin mass (Hb _mass ), a key determinant of arterial oxygen‐carrying capacity, but following descent this adaptation can regress toward baseline within 7 days. Long‐term heat acclimation has emerged as an alternative stimulus for Hb _mass expansion; however, whether post‐altitude passive‐heat exposure can preserve altitude‐induced increases in Hb _mass remains unclear. Furthermore, the extent to which any preservation of Hb _mass is supported by sustained erythropoietin (EPO) production, and whether this support is mediated by plasma volume expansion or acute alterations in renal haemodynamics, has yet to be explored. Twenty‐one healthy adults (8F) sojourned at 3800 m for 14 days and, following descent to 1250 m, were allocated to either hot‐water immersion (HWI; 45 min at 40°C for 4 days; n  = 11) or control (CON; n  = 10). Hb _mass , intravascular volumes (carbon monoxide rebreathing) and circulating EPO were measured on high‐altitude day 1 (HA1), day 14 (HA14), and post‐descent day 5 (P5). Renal‐artery blood velocity (Doppler‐ultrasound) was measured before and after HWI on the day of descent. Hb _mass increased by 24 g [95% CI: 8, 40] across all participants during the altitude sojourn ( P  = 0.005). Following descent, Hb _mass decreased in CON (∆ = −18 g [95% CI: −36, 0], P  = 0.045) but was maintained in HWI (∆ = +9 g [95% CI: −8, 26], P  = 0.285). Circulating EPO declined after descent ( P  < 0.001) with no between‐condition difference at P5 ( P  = 0.239), despite a transient reduction in renal‐artery blood velocity following HWI ( P  = 0.025) and similar plasma volume expansion across groups (time: P  < 0.001). Hot‐water immersion offers a practical, lower‐impact alternative to exercise‐heat methods for preserving altitude‐derived Hb _mass expansion, although the mechanisms underlying this response remain elusive.

Facial cooling can increase ventilation and augment the hypoxic ventilatory response. Whole body cooling increases both carotid body tonic activity and sensitivity; however, whether isolated facial cooling induces similar carotid body hyperexcitability was unknown. We investigated whether facial cooling alters carotid body function by assessing tonic activity and hypoxic sensitivity. Fourteen healthy adults (11 M/3 F; age 26 ± 4 years) completed a counterbalanced, crossover study involving transient hyperoxia and poikilocapnic hypoxia (9.5% O ₂ ) under thermoneutral (facial temperature: 34.2 ± 1.2°C) and facial cooling (19.4 ± 3.3°C) conditions. Carotid body tonic activity was inferred from the ventilatory suppression during transient hyperoxia. Sensitivity was assessed via the change in end‐tidal CO ₂ () relative to oxygen saturation () during hypoxia. Facial cooling induced hyperventilation, evidenced by reduced (35 ± 8 vs. 41 ± 3 mmHg; P = 0.008), and elevated ventilatory equivalent for CO ₂ production (28 ± 6 vs. 23 ± 2; P = 0.02). Carotid body tonic activity did not differ between facial cooling and thermoneutral conditions, but carotid body sensitivity was reduced during facial cooling (0.20 ± 0.14 vs. 0.28 ± 0.13 mmHg/%; P = 0.044). The reduction in experienced during facial cooling correlated with enhanced carotid body tonic activity ( R ² = 0.39, P = 0.022) and reduced sensitivity ( R ² = 0.33, P = 0.03). Collectively, facial cooling induces hyperventilation and the attendant hypocapnia reduces carotid body sensitivity. Although this hyperventilation is related to carotid body tonic activity, facial cooling likely produces a cold shock response that stimulates ventilation separately from the carotid body. These findings offer new insights on the interaction between stimuli relevant to outdoor activities in cold environments (e.g., snow shovelling, mountaineering, cold water swimming) and carotid body function.

High‐altitude acclimatisation increases muscle sympathetic nerve activity (MSNA) via activation of the arterial chemoreflex, pulmonary arterial baroreceptors and resetting of the sympathetic vascular baroreflex. However attempting to silence these mechanisms only partially normalises MSNA, implicating other contributory mechanisms. Increased oxidant production may modulate central sympathetic outflow, while potentially modifying chemosensitivity and vasomotor signalling to the peripheral and pulmonary vasculature. Therefore we tested the hypothesis that blunting oxidative stress would reduce MSNA at high altitude. MSNA (microneurography of the peroneal nerve), continuous arterial pressure (photoplethysmography), vascular tone (duplex ultrasound of the brachial artery), pulmonary artery systolic pressure (PASP, echocardiography) and carotid body tonic activity (1‐min hyperoxia) were measured pre‐ and post‐ascorbic acid infusion (200 mg/min for 15‐min and then 40 mg/min) in healthy lowlanders ( n = 15) after 3–7 days of high‐altitude exposure (3800 m). Ascorbic acid infusion improved the redox environment, determined by an increase in whole cell nuclear factor erythroid 2‐related factor 2 activity ( P = 0.005). Post‐infusion MSNA burst frequency (−2 ± 2 bursts/min, P = 0.007) and incidence (−5 ± 4 bursts/100 heartbeats (HB), P = 0.006) decreased. However the infusion increased mean arterial (9 ± 4 mmHg, P ≤0.001), systolic (11 ± 8 mmHg, P  ≤ 0.004) and diastolic pressure (7 ± 4 mmHg, P  ≤ 0.001) and total peripheral resistance ( P = 0.013) concomitantly with a reduction in brachial diameter (−0.12 ± 0.14 mm, P = 0.002). Carotid body tonic activity ( P = 0.247) and PASP ( P = 0.365) remained unchanged by ascorbic acid infusion. In conclusion improving the antioxidant environment lowered MSNA at high altitude; however the small reduction is likely a consequence of the increased blood pressure secondary to the blunting of hypoxic vasodilation rather than a direct effect on sympathetic outflow. image Key points: High‐altitude acclimatisation increases muscle sympathetic nerve activity (MSNA) from sea level values. Pulmonary artery systolic pressure (PASP), peripheral arterial chemoreflex and high altitude‐induced hypovolaemia are involved in the increase in MSNA; however current evidence indicates additional contributory mechanisms. Hypoxia associated with high altitude results in an increase in the production of reactive oxygen species (ROS), which may be sympathoexcitatory. Therefore we tested the hypothesis that improving the redox environment using an ascorbic acid infusion would lower sympathetic nerve activity. After the infusion, sympathetic nerve activity was reduced alongside an increase in vascular tone and elevation in blood pressure. The reduction in MSNA occurred independently of changes in PASP and chemoreflex activity. Our findings demonstrate that ROS elevates sympathetic nerve activity at high altitude; however this reduction is likely a result of the elevated blood pressure after the blunting of hypoxic vasodilation.

Hemoglobin concentration is often interpreted as a marker for total hemoglobin mass in studies investigating high‐altitude adaptation. However, hemoglobin concentration is determined by both plasma volume and total hemoglobin mass. Therefore, using hemoglobin concentration as a marker for hemoglobin mass can obscure variation in total hemoglobin mass and/or plasma volume and lead to flawed conclusions about adaptation. In this short commentary, we highlight examples from athletic, clinical and high‐altitude populations and responses to environmental stressors illustrating the dissociations between intravascular volumes and hemoglobin concentration. The reliance on hemoglobin concentration has reinforced the prevailing, but potentially incorrect, interpretation of blunted hypoxia‐induced erythropoiesis in Tibetan and Ethiopian highlanders. We argue that measures of plasma volume and total hemoglobin mass, which can easily be obtained using the carbon monoxide rebreathing technique, provide more physiologically relevant phenotypes. We propose that future genetic and evolutionary studies of high‐altitude adaptation should move beyond hemoglobin concentration and focus on measurements of total hemoglobin mass and intravascular volumes.

Long‐term heat acclimation has been shown to elevate haemoglobin mass (Hb _mass ) and enhance maximal oxygen consumption (). To date, however, all evidence derives from exercise‐induced heat stress, making it unclear whether passive strategies, which allow athletes to maintain training intensities, can produce similar adaptations. Moreover, while heat‐induced increases in are often attributed to haematological changes, adaptation of other convective components of oxygen transport may underpin these improvements. To investigate whether 5 weeks of hot‐water immersion (HWI) would enhance , 10 well‐trained runners (nine male; = 64.5 ± 8.1 mL min ⁻¹ kg ⁻¹ ) completed a within‐subject, counterbalanced cross‐over intervention involving HWI (5 × 45 min week ⁻¹ ; ≥40°C) and a time‐matched control, alongside habitual training. Haematological and cardiac adaptations were assessed using carbon‐monoxide rebreathing (in duplicate) and four‐dimensional (4D) speckle‐tracking echocardiography, respectively. HWI increased Hb _mass (+33 g, P < 0.001; [95% confidence interval (CI) 18 to 49]), blood volume (+284 mL, P < 0.001; [95% CI 113 to 455]) and left ventricular end‐diastolic volume (LVEDV; +10 mL, P < 0.001; [95% CI 6 to 13]), without altering 4D global peak longitudinal strain, diastolic‐strain rate or diastolic‐filling rate. These changes facilitated a 2.7 mL kg ⁻¹ min ⁻¹ improvement in ( P < 0.001; [95% CI 1.4 to 4.1]) and a 0.8 km h ⁻¹ increase in treadmill speed at ( P < 0.001; [95% CI 0.5 to 1.1]). Best subset regression analysis identified Hb _mass as the strongest independent predictor of (β = 3.8, P < 0.001), with cardiac adaptations contributing additional explanatory value ( R ² = 0.825 fixed effects; 0.961 full model). Our findings demonstrate that passive heat exposure elicits coordinated adaptations to multiple convective components of the oxygen transport chain, and represents a physiologically effective and sustainable strategy for enhancing in well‐trained populations. image Key points: Long‐term heat acclimation can increase haemoglobin mass and maximal oxygen uptake; whether passive heat can produce similar effects was previously unknown. Whether cardiac adaptation contributes to the heat‐induced improvements in maximal oxygen consumption remains unclear. In a within‐subject, counterbalanced cross‐over design, 10 well‐trained runners completed 5 weeks of hot‐water immersion alongside their normal training and a time‐matched control period. Passive heating increased haemoglobin mass, total blood volume, and left‐ventricular end‐diastolic volume. These haematological and cardiac adaptations explained the observed improvement in maximal oxygen uptake, indicating that passive heat can enhance aerobic performance via coordinated effects across multiple components of the oxygen transport chain.

Brain‐derived neurotrophic factor (BDNF) is an essential mediator of exercise‐induced neuroplasticity. The majority of BDNF in circulation (∼99%) is stored bound to platelets. Platelet activation by exercise stimulates the release of their contents, representing a dynamic, bioavailable pool of BDNF. Hypoxia also independently activates platelets; therefore the combination of these stressors provides a unique model to examine the role of platelets in liberating BDNF and to quantify its flux across the brain during exercise. Twelve healthy adults (six women; 28 ± 4 years) performed exercise to exhaustion at sea level (340 m) and after 6–8 days at high altitude (3800 m) in a repeated‐measures cross‐over design. Simultaneous radial arterial and internal jugular venous blood samples were collected within the last 2 min of maximal exercise to quantify BDNF across the brain, alongside platelet concentration and platelet factor 4 (PF4), another neurogenic factor and a biomarker of platelet activation. At sea level, maximal exercise doubled free BDNF ( P < 0.001) with no difference between arterial and venous circulations ( P = 0.849). At high altitude, there was a pronounced veno‐arterial difference indicating net release of BDNF ( P = 0.003), and in addition, exercise caused a similar doubling in free BDNF ( P < 0.001). Platelet concentration decreased by a third across the brain with exercise at high altitude ( P = 0.002), but not sea level, and PF4 release was strongly correlated with BDNF release (r = 0.61, P < 0.001). Platelet activation across the human brain during exercise and hypoxia liberates BDNF and PF4 and may contribute to the neurotrophic effect of exercise. image Key points: Brain‐derived neurotrophic factor (BDNF) is a protein involved in synaptic plasticity and neuronal growth, and it may mediate some of the neuroprotective effects of exercise. The majority of BDNF in circulation is stored bound to platelets, released as free BDNF into the plasma by platelet activation (e.g. by exercise or hypoxia). At sea level, maximal exercise doubled free BDNF to a similar extent between arterial and venous circulations. At high altitude, at rest, a net release of BDNF from the brain was observed (veno‐arterial difference), with a similar doubling in free BDNF with maximal exercise. Platelet factor 4, a metric of platelet activation, was correlated with BDNF release, indicating that platelet activation offers an explanation for the increased liberation of BDNF during exercise and hypoxia.

Cholesterol, triglycerides, high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), and very-low-density lipoproteins (VLDLs) were evaluated in chimpanzees at Tacugama Chimpanzee Sanctuary, Sierra Leone. Blood from 75 visually healthy chimpanzees was collected, centrifuged within one hour of collection, and analyzed at Choithram Hospital within 24 h. Statistical analyses assessed differences and interactions based on age, body condition score (BCS), housing group, and sex. HDLs varied widely by housing group; HDLs and LDLs were higher in males than in females. Cholesterol and LDLs were higher in prepubertal individuals while VLDLs and triglycerides were higher in postpubertal individuals. Lipid biomarker differences by age and age ∗ sex statistical interactions were not observed. These data represent a novel compilation of serum lipid biomarkers from a large population of sanctuary-housed Western chimpanzees (Pan troglodytes verus) within a range country, a population not previously studied with regard to serum lipid biomarkers. This study has documented significant differences compared to known values from managed chimpanzees and human reference ranges. The relationship of serum lipid biomarkers with health and disease in great apes remains understudied, but the present data set provides a basis for future studies to ascertain whether these differences are healthy biomarker variations or represent an elevated risk factor for disease.