Local temperature-sensitive mechanisms are important mediators of limb tissue hyperemia in the heat-stressed human at rest and during small muscle mass exercise.

Limb tissue and systemic blood flow increases with heat stress, but the underlying mechanisms remain poorly understood. Here, we tested the hypothesis that heat stress-induced increases in limb tissue perfusion are primarily mediated by local temperature-sensitive mechanisms. Leg and systemic temperatures and hemodynamics were measured at rest and during incremental single-legged knee extensor exercise in 15 males exposed to 1 h of either systemic passive heat-stress with simultaneous cooling of a single leg (n=8) or isolated leg heating or cooling (n=7). Systemic heat-stress increased core, skin and heated leg blood (Tb) temperatures, cardiac output and heated leg blood flow (LBF, 0.6 ± 0.1 l.min(-1); P0.05). Increased heated leg deep tissue BF was closely related to Tb (R(2) = 0.50; P0.05), despite unchanged systemic temperatures and hemodynamics. During incremental exercise, heated LBF was consistently maintained ~ 0.6 l.min(-1) higher than that in the cooled leg (P<0.01), with LBF and vascular conductance in both legs showing a strong correlation with their respective local Tb (R(2) = 0.85 and 0.95, P<0.05). We conclude that local temperature-sensitive mechanisms are important mediators in limb tissue perfusion regulation both at rest and during small-muscle mass exercise in hyperthermic humans.The invasive study was partially funded by Gatorade Sports Science Institute, PepsiCo

Whole body hyperthermia, but not skin hyperthermia, accelerates brain and locomotor limb circulatory strain and impairs exercise capacity in humans

Cardiovascular strain and hyperthermia are thought to be important factors limiting exercise capacity in heat-stressed humans; however, the contribution of elevations in skin (Tsk) vs. whole body temperatures on exercise capacity has not been characterised. To ascertain their relationships with exercise capacity, blood temperature (TB), oxygen uptake (V̇O2), brain perfusion (MCA Vmean), locomotor limb haemodynamics, and haematological parameters were assessed during incremental cycling exercise with elevated skin (mild hyperthermia; HYPmild), combined core and skin temperatures (moderate hyperthermia; HYPmod), and under control conditions. Both hyperthermic conditions increased Tsk vs. control (6.2 ± 0.2 °C; P < 0.001), however, only HYPmod increased resting TB, leg blood flow and cardiac output (Q̇), but not MCA Vmean. Throughout exercise, Tsk remained elevated in both hyperthermic conditions, whereas only TB was greater in HYPmod. At exhaustion, oxygen uptake and exercise capacity were reduced in HYPmod in association with lower leg blood flow, MCA Vmean and MAP, but similar maximal heart rate and TB. The attenuated brain and leg perfusion with hyperthermia was associated with a plateau in MCA and two-legged vascular conductance (VC). Mechanistically, the falling MCA VC was coupled to reductions in PaCO2 whereas the plateau in leg vascular conductance was related to markedly elevated plasma [NA] and a plateau in plasma ATP. These findings reveal that whole-body hyperthermia, but not skin hyperthermia, compromises exercise capacity in heat-stressed humans through the early attenuation of brain and active muscle blood flow.This study was supported by a grant from the Gatorade Sports Science Institute, PepsiCo Inc, USA. The views contained within this document are those of the authors and do not necessarily reflect those of PepsiCo Inc

Physiological Function during Exercise and Environmental Stress in Humans—An Integrative View of Body Systems and Homeostasis

Claude Bernard’s milieu intérieur (internal environment) and the associated concept of homeostasis are fundamental to the understanding of the physiological responses to exercise and environmental stress. Maintenance of cellular homeostasis is thought to happen during exercise through the precise matching of cellular energetic demand and supply, and the production and clearance of metabolic by-products. The mind-boggling number of molecular and cellular pathways and the host of tissues and organ systems involved in the processes sustaining locomotion, however, necessitate an integrative examination of the body’s physiological systems. This integrative approach can be used to identify whether function and cellular homeostasis are maintained or compromised during exercise. In this review, we discuss the responses of the human brain, the lungs, the heart, and the skeletal muscles to the varying physiological demands of exercise and environmental stress. Multiple alterations in physiological function and differential homeostatic adjustments occur when people undertake strenuous exercise with and without thermal stress. These adjustments can include: Hyperthermia; hyperventilation; cardiovascular strain with restrictions in brain, muscle, skin and visceral organs blood flow; greater reliance on muscle glycogen and cellular metabolism; alterations in neural activity; and, in some conditions, compromised muscle metabolism and aerobic capacity. Oxygen supply to the human brain is also blunted during intense exercise, but global cerebral metabolism and central neural drive are preserved or enhanced. In contrast to the strain seen during severe exercise and environmental stress, a steady state is maintained when humans exercise at intensities and in environmental conditions that require a small fraction of the functional capacity. The impact of exercise and environmental stress upon whole-body functions and homeostasis therefore depends on the functional needs and differs across organ systems

Mechanisms for the control of local tissue blood flow during thermal interventions: influence of temperature-dependent ATP release from human blood and endothelial cells

© 2016 The Authors. Local tissue perfusion changes with alterations in temperature during heating and cooling, but the thermosensitivity of the vascular ATP signalling mechanisms for control of blood flow during thermal interventions remains unknown. Here we tested the hypotheses that the release of the vasodilator mediator ATP from human erythrocytes, but not from endothelial cells or other blood constituents, is sensitive to both increases and reductions in temperature and that increasing intravascular ATP availability with ATP infusion would potentiate thermal hyperaemia in limb tissues. We first measured blood temperature (Tb), brachial artery blood flow (BABF) and plasma [ATP] during passive arm heating and cooling in healthy males and found they increased by 3.0 ± 1.2 ºC, 105 ± 25 ml min-1 °C-1 and 2-fold (all P<0.05) with heating, but decreased or remained unchanged with cooling. In additional males, intrabrachial artery ATP infusion increased skin and deep tissue perfusion to levels equal or above thermal hyperaemia. In isolated erythrocyte samples exposed to different temperatures, ATP release increased 1.9-fold from 33°C to 39°C (P<0.05) and declined by ~50% at 20°C (P<0.05), but no changes were observed in cultured human endothelial cells, plasma or serum samples. In conclusion, increases in plasma [ATP] and skin and deep tissue perfusion with limb heating are associated with elevations in ATP release from erythrocytes, but not from endothelial cells or other blood constituents. Erythrocyte ATP release is also sensitive to temperature reductions, suggesting erythrocytes may function as thermal sensors and ATP signalling generators for tissue perfusion control during thermal interventions

Cross Adaptation - Heat and Cold Adaptation to Improve Physiological and Cellular Responses to Hypoxia

To prepare for extremes of heat, cold or low partial pressures of O2, humans can undertake a period of acclimation or acclimatization to induce environment specific adaptations e.g. heat acclimation (HA), cold acclimation (CA), or altitude training. Whilst these strategies are effective, they are not always feasible, due to logistical impracticalities. Cross adaptation is a term used to describe the phenomenon whereby alternative environmental interventions e.g. HA, or CA, may be a beneficial alternative to altitude interventions, providing physiological stress and inducing adaptations observable at altitude. HA can attenuate physiological strain at rest and during moderate intensity exercise at altitude via adaptations allied to improved oxygen delivery to metabolically active tissue, likely following increases in plasma volume and reductions in body temperature. CA appears to improve physiological responses to altitude by attenuating the autonomic response to altitude. While no cross acclimation-derived exercise performance/capacity data have been measured following CA, post-HA improvements in performance underpinned by aerobic metabolism, and therefore dependent on oxygen delivery at altitude, are likely. At a cellular level, heat shock protein responses to altitude are attenuated by prior HA suggesting that an attenuation of the cellular stress response and therefore a reduced disruption to homeostasis at altitude has occurred. This process is known as cross tolerance. The effects of CA on markers of cross tolerance is an area requiring further investigation. Because much of the evidence relating to cross adaptation to altitude has examined the benefits at moderate to high altitudes, future research examining responses at lower altitudes should be conducted given that these environments are more frequently visited by athletes and workers. Mechanistic work to identify the specific physiological and cellular pathways responsible for cross adaptation between heat and altitude, and between cold and altitude, is warranted, as is exploration of benefits across different populations and physical activity profiles

Heat, Hydration and the Human Brain, Heart and Skeletal Muscles

People undertaking prolonged vigorous exercise experience substantial bodily fluid losses due to thermoregulatory sweating. If these fluid losses are not replaced, endurance capacity may be impaired in association with a myriad of alterations in physiological function, including hyperthermia, hyperventilation, cardiovascular strain with reductions in brain, skeletal muscle and skin blood perfusion, greater reliance on muscle glycogen and cellular metabolism, alterations in neural activity and, in some conditions, compromised muscle metabolism and aerobic capacity. The physiological strain accompanying progressive exercise-induced dehydration to a level of ~ 4% of body mass loss can be attenuated or even prevented by: (1) ingesting fluids during exercise, (2) exercising in cold environments, and/or (3) working at intensities that require a small fraction of the overall body functional capacity. The impact of dehydration upon physiological function therefore depends on the functional demand evoked by exercise and environmental stress, as cardiac output, limb blood perfusion and muscle metabolism are stable or increase during small muscle mass exercise or resting conditions, but are impaired during whole-body moderate to intense exercise. Progressive dehydration is also associated with an accelerated drop in perfusion and oxygen supply to the human brain during submaximal and maximal endurance exercise. Yet their consequences on aerobic metabolism are greater in the exercising muscles because of the much smaller functional oxygen extraction reserve. This review describes how dehydration differentially impacts physiological function during exercise requiring low compared to high functional demand, with an emphasis on the responses of the human brain, heart and skeletal muscles.Gatorade Sports Science Institute (GSSI

Integrative human cardiovascular responses to hyperthermia

Progressive whole-body hyperthermia with passive heat stress is associated with a host of physiological adjustments. These include large increases in peripheral blood flow and cardiac output and a smaller selective redistribution of blood flow from the cerebral and visceral tissues to the limbs, head, and torso, with perfusion pressure being only slightly reduced. Aerobic metabolism also increases in these conditions, but the magnitude is small in absolute terms, suggesting a predominant role of thermosensitive mechanisms in passive hyperthermia-induced cardiovascular adjustments. Although exercise heat stress requires substantially greater blood flow requirements compared to passive heat stress alone, the magnitude of this hyperemic response is less than would be expected given the extent to which both conditions independently increase blood flow in isolation. As a result, submaximal exercise limb blood flow is only slightly higher during small muscle-mass exercise in the heat, and is similar to control conditions during whole-body exercise. When exercise intensity is increased further towards maximal levels, the superimposition of heat stress leads to earlier reductions in regional and systemic blood perfusion, compromised locomotor limb aerobic metabolism, and ultimately results in impaired endurance capacity. This chapter provides an integrative overview of the human cardiovascular response to passive heat stress and exercise heat stress, with emphasis on its consequences on exercise performance in the heat