AltitudeOmics: The Integrative Physiology of Human Acclimatization to Hypobaric Hypoxia and Its Retention upon Reascent.

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention

Cross-sectional and longitudinal associations between different exercise types and food cravings in free-living healthy young adults

Introduction: An increase in energy intake due to alterations in hedonic appetite sensations may, at least in part, contribute to lower-than-expected weight loss in exercise interventions. The aim of this study was to examine cross-sectional and longitudinal associations between habitual exercise participation and food cravings in free-living young adults. Methods: A total of 417 adults (49% male, 28 ± 4 years) reported frequency and duration of walking, aerobic exercise, resistance exercise and other exercise at baseline and every 3 months over a 12-month period. Food cravings were assessed via the Control of Eating Questionnaire at baseline and 12-month follow-up. Results: Cross-sectional analyses revealed more frequent cravings for chocolate and a greater difficulty to resist food cravings in women compared to men (p < 0.01). Only with resistance exercise significant sex by exercise interaction effects were observed with favorable responses in men but not in women. Significant main effects were shown for walking and aerobic exercise with exercisers reporting more frequent food cravings for chocolate and fruits and greater difficulty to resist eating compared to non-exercisers (p < 0.05). Longitudinal analyses revealed significant interaction effects for other exercise (p < 0.05) with favorable results in men but not women. Furthermore, significant main effects were observed for aerobic exercise, resistance exercise and total exercise with an increase in exercise being associated with a reduced difficulty to resist food cravings (p < 0.05). Discussion: The association between exercise participation and hedonic appetite sensations varies by exercise type and sex. Even though exercise was associated with more frequent and greater difficulty to food cravings in the cross-sectional analyses, which may be attributed to greater energy demands, longitudinal results indicate beneficial effects of increased exercise on appetite control, particularly in men

Estimulação cerebral na promoção da saúde e melhoria do desempenho físico

O avanço tecnológico das últimas décadas tem proporcionado o uso eficaz de técnicas não-invasivas na neuromodulação cerebral. Atualmente, as principais técnicas de neuromodulação são a estimulação magnética transcraniana (EMT) e a estimulação transcraniana por corrente contínua (ETCC). Por meio de revisão da literatura, o presente estudo aborda: a) história da estimulação cerebral; b) mecanismos de ação estudados através da neurofisiologia motora, farmacologia, neuroimagem e animais experimentais; c) perspectivas de aplicações da estimulação cerebral para promoção da saúde e melhoria do desempenho físico, incluindo o controle autonômico cardíaco e hipotensão pós-exercício, o controle de apetite e a modulação da fadiga e desempenho físico; e d) aspectos de segurança referentes ao uso da ETCC. Dessa forma, a ETCC parece ser uma técnica efetiva e segura para modular a função cerebral e podemos vislumbrar algumas perspectivas de aplicação no âmbito da ingestão alimentar, saúde cardiovascular e desempenho físico.The technological advances of the last decades have provided the effective use of noninvasive techniques in neuromodulation with concomitant health benefits. Currently, the main neuromodulation techniques are transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Through literature review, this study addresses the a) history of brain stimulation and the b) mechanisms of action studied by motor neurophysiology, pharmacology, neuroimaging, and experimental animals. Moreover, it is presented the c) perspectives for applications of brain stimulation for promoting health and improving physical performance, including cardiac autonomic control and post-exercise hypotension, control and modulation of appetite, fatigue and physical performance. Finally, we describe d) the security aspects related to the use of tDCS. Thus, tDCS seems to be an effective and safe technique to modulate brain function and suggests some application associated to food intake, cardiovascular health and physical performance

AltitudeOmics: effects of 16 days acclimatization to hypobaric hypoxia on muscle oxygen extraction during incremental exercise.

Acute altitude exposure lowers arterial oxygen content ([Formula: see text]) and cardiac output ([Formula: see text]) at peak exercise, whereas O &lt;sub&gt;2&lt;/sub&gt; extraction from blood to working muscles remains similar. Acclimatization normalizes [Formula: see text] but not peak [Formula: see text] nor peak oxygen consumption (V̇o &lt;sub&gt;2peak&lt;/sub&gt; ). To what extent acclimatization impacts muscle O &lt;sub&gt;2&lt;/sub&gt; extraction remains unresolved. Twenty-one sea-level residents performed an incremental cycling exercise to exhaustion near sea level (SL), in acute (ALT1) and chronic (ALT16) hypoxia (5,260 m). Arterial blood gases, gas exchange at the mouth and oxy- (O &lt;sub&gt;2&lt;/sub&gt; Hb) and deoxyhemoglobin (HHb) of the vastus lateralis were recorded to assess arterial O &lt;sub&gt;2&lt;/sub&gt; content ([Formula: see text]), [Formula: see text], and V̇o &lt;sub&gt;2&lt;/sub&gt; . The HHb-V̇o &lt;sub&gt;2&lt;/sub&gt; slope was taken as a surrogate for muscle O &lt;sub&gt;2&lt;/sub&gt; extraction. During moderate-intensity exercise, HHb-V̇o &lt;sub&gt;2&lt;/sub&gt; slope increased to a comparable extent at ALT1 (2.13 ± 0.94) and ALT16 (2.03 ± 0.88) compared with SL (1.27 ± 0.12), indicating increased O &lt;sub&gt;2&lt;/sub&gt; extraction. However, the HHb/[Formula: see text] ratio increased from SL to ALT1 and then tended to go back to SL values at ALT16. During high-intensity exercise, HHb-V̇o &lt;sub&gt;2&lt;/sub&gt; slope reached a break point beyond which it decreased at SL and ALT1, but not at ALT16. Increased muscle O &lt;sub&gt;2&lt;/sub&gt; extraction during submaximal exercise was associated with decreased [Formula: see text] in acute hypoxia. The significantly greater muscle O &lt;sub&gt;2&lt;/sub&gt; extraction during maximal exercise in chronic hypoxia is suggestive of an O &lt;sub&gt;2&lt;/sub&gt; reserve.NEW &amp; NOTEWORTHY During incremental exercise muscle deoxyhemoglobin (HHb) and oxygen consumption (V̇o &lt;sub&gt;2&lt;/sub&gt; ) both increase linearly, and the slope of their relationship is an indirect index of local muscle O &lt;sub&gt;2&lt;/sub&gt; extraction. The latter was assessed at sea level, in acute and during chronic exposure to 5,260 m. The demonstrated presence of a muscle O &lt;sub&gt;2&lt;/sub&gt; extraction reserve during chronic exposure is coherent with previous studies indicating both limited muscle oxidative capacity and decrease in motor drive

AltitudeOmics: enhanced cerebrovascular reactivity and ventilatory response to CO2 with high-altitude acclimatization and reexposure.

The present study is the first to examine the effect of high-altitude acclimatization and reexposure on the responses of cerebral blood flow and ventilation to CO2. We also compared the steady-state estimates of these parameters during acclimatization with the modified rebreathing method. We assessed changes in steady-state responses of middle cerebral artery velocity (MCAv), cerebrovascular conductance index (CVCi), and ventilation (V(E)) to varied levels of CO2 in 21 lowlanders (9 women; 21 ± 1 years of age) at sea level (SL), during initial exposure to 5,260 m (ALT1), after 16 days of acclimatization (ALT16), and upon reexposure to altitude following either 7 (POST7) or 21 days (POST21) at low altitude (1,525 m). In the nonacclimatized state (ALT1), MCAv and V(E) responses to CO2 were elevated compared with those at SL (by 79 ± 75% and 14.8 ± 12.3 l/min, respectively; P = 0.004 and P = 0.011). Acclimatization at ALT16 further elevated both MCAv and Ve responses to CO2 compared with ALT1 (by 89 ± 70% and 48.3 ± 32.0 l/min, respectively; P &lt; 0.001). The acclimatization gained for V(E) responses to CO2 at ALT16 was retained by 38% upon reexposure to altitude at POST7 (P = 0.004 vs. ALT1), whereas no retention was observed for the MCAv responses (P &gt; 0.05). We found good agreement between steady-state and modified rebreathing estimates of MCAv and V(E) responses to CO2 across all three time points (P &lt; 0.001, pooled data). Regardless of the method of assessment, altitude acclimatization elevates both the cerebrovascular and ventilatory responsiveness to CO2. Our data further demonstrate that this enhanced ventilatory CO2 response is partly retained after 7 days at low altitude

AltitudeOmics: effect of ascent and acclimatization to 5260 m on regional cerebral oxygen delivery.

Cerebral hypoxaemia associated with rapid ascent to high altitude can be life threatening; yet, with proper acclimatization, cerebral function can be maintained well enough for humans to thrive. We investigated adjustments in global and regional cerebral oxygen delivery (DO2) as 21 healthy volunteers rapidly ascended and acclimatized to 5260 m. Ultrasound indices of cerebral blood flow in internal carotid and vertebral arteries were measured at sea level, upon arrival at 5260 m (ALT1; atmospheric pressure 409 mmHg) and after 16 days of acclimatization (ALT16). Cerebral DO2 was calculated as the product of arterial oxygen content and flow in each respective artery and summed to estimate global cerebral blood flow. Vascular resistances were calculated as the quotient of mean arterial pressure and respective flows. Global cerebral blood flow increased by ∼70% upon arrival at ALT1 (P &lt; 0.001) and returned to sea-level values at ALT16 as a result of changes in cerebral vascular resistance. A reciprocal pattern in arterial oxygen content maintained global cerebral DO2 throughout acclimatization, although DO2 to the posterior cerebral circulation was increased by ∼25% at ALT1 (P = 0.032). We conclude that cerebral DO2 is well maintained upon acute exposure and acclimatization to hypoxia, particularly in the posterior and inferior regions of the brain associated with vital homeostatic functions. This tight regulation of cerebral DO2 was achieved through integrated adjustments in local vascular resistances to alter cerebral perfusion during both acute and chronic exposure to hypoxia

AltitudeOmics: cerebral autoregulation during ascent, acclimatization, and re-exposure to high altitude and its relation with acute mountain sickness.

Cerebral autoregulation (CA) acts to maintain brain blood flow despite fluctuations in perfusion pressure. Acute hypoxia is thought to impair CA, but it is unclear if CA is affected by acclimatization or related to the development of acute mountain sickness (AMS). We assessed changes in CA using transfer function analysis of spontaneous fluctuations in radial artery blood pressure (indwelling catheter) and resulting changes in middle cerebral artery blood flow velocity (transcranial Doppler) in 21 active individuals at sea level upon arrival at 5,260 m (ALT1), after 16 days of acclimatization (ALT16), and upon re-exposure to 5,260 m after 7 days at 1,525 m (POST7). The Lake Louise Questionnaire was used to evaluate AMS symptom severity. CA was impaired upon arrival at ALT1 (P &lt; 0.001) and did not change with acclimatization at ALT16 or upon re-exposure at POST7. CA was not associated with AMS symptoms (all R &lt; 0.50, P &gt; 0.05). These findings suggest that alterations in CA are an intrinsic consequence of hypoxia and are not directly related to the occurrence or severity of AMS

Cardiopulmonary Fitness Correlates with Regional Cerebral Grey Matter Perfusion and Density in Men with Coronary Artery Disease

PURPOSE: Physical activity is associated with positive effects on the brain but there is a paucity of clinical neuroimaging data in patients with coronary artery disease (CAD), a cardiovascular condition associated with grey matter loss. The purpose of this study was to determine which brain regions are impacted by cardiopulmonary fitness and with the change in fitness after 6 months of exercise-based cardiac rehabilitation. METHODS: CAD patients underwent magnetic resonance imaging at baseline, and peak volume of oxygen uptake during exercise testing (VO(2Peak)) was measured at baseline and after 6 months of training. T1-weighted structural images were used to perform grey matter (GM) voxel-based morphometry (VBM). Pseudo-continuous arterial spin labeling (pcASL) was used to produce cerebral blood flow (CBF) images. VBM and CBF data were tested voxel-wise using VO(2Peak) and age as explanatory variables. RESULTS: In 30 men with CAD (mean age 65±7 years), VBM and CBF identified 7 and 5 respective regions positively associated with baseline VO(2Peak). These included the pre- and post-central, paracingulate, caudate, hippocampal regions and converging findings in the putamen. VO(2Peak) increased by 20% at follow-up in 29 patients (t = 9.6, df = 28, p<0.0001). Baseline CBF in the left post-central gyrus and baseline GM density in the right putamen predicted greater change in VO(2Peak). CONCLUSION: Perfusion and GM density were associated with fitness at baseline and with greater fitness gains with exercise. This study identifies new neurobiological correlates of fitness and demonstrates the utility of multi-modal MRI to evaluate the effects of exercise in CAD patients