Optimising heat acclimation to attenuate physiological and cellular stress in hypoxia

Exercise in extreme environmental conditions places increased systemic stress on the body. Environmental conditions in which physical activity occurs (such as for athletic competition or occupational and military endeavours) include dry and humid heat, where internal body temperatures exceeding 40.6°C can be fatal, and at altitude where ascents above 2,500m can lead to illness, particularly when combined with physical activity. In these extreme environments, the difference from typical habitual normothermic, normoxic conditions presents a significant physiological challenge to regulate temperature and reduce systemic hypoxia resulting from reductions in inspired oxygen content.

The human body has a unique ability to adapt both physiologically and behaviourally, in order to tolerate the increases in physiological and cellular strain induced by changes in environmental conditions. Altitude acclimation/acclimatization defines adaptive responses occurring in simulated (low oxygen concentration) or actual (low barometric pressure) environments. Physiological adaptations to this altitude training paradigm include red blood cell proliferation following erythropoiesis , angiogenesis, and mitochondrial biogenesis. These adaptations improve oxygen delivery and utilisation, thus reducing anaerobic contributions to physical work at a given intensity translating to an increased ability to perform physical activity requiring aerobic metabolism. Provision of altitude training facilities is problematic for some individuals, as is the ability to reside within the environment for extended periods within a day, and for consecutive days for up to four weeks.

Heat adaptations are attainable in periods ranging from four to ten consecutive days, with daily exposure requirements optimised at a maximum of 100 minutes, with as little of 30 minutes of moderate intensity exercise required in hot, humid conditions (≥30°C and ≥40% relative humidity). Thus, heat acclimation/acclimatization may be more attainable than altitude acclimation/acclimatization, and may be equally effective at reducing the physiological strain of these unfamiliar conditions. In contrast to the primarily haematological adaptations elicited at altitude, heat derived adaptations are multisystemic with homeostatic reductions in basal body temperature, improved sweat responses to facilitate heat dissipation via evaporation and blood plasma expansion improving cardiovascular function. Each of these contributes to a favourable attenuation in physiological strain at rest and during physical activity in both the hot, and cool conditions.

Numerous data evidence acclimation or acclimatization to environmental stress in isolation, using repeated actual or simulated exposures, as an effective intervention which allows an individual to maintain physical activity, and/or attenuate physiological strain. At present, it is unknown whether acclimation to one environmental stressor might offer protection in a different environmental condition sharing similar physiological consequences, though this phenomenon has been proposed in a number of recent reviews.

Animal models, and a small number of human studies have begun to experimentally elucidate mechanisms associated with cross adaptation. Cross adaptation proposes that acclimation or acclimatization to one environmental extreme, for example, heat stress or hypoxia, will facilitate maintenance of physical activity and/or attenuate physiological strain in a different environment. Mechanisms for cross adaptation can be subdivided into physiological adaptations (cross acclimation) and cellular adaptation (cross tolerance). Cross acclimation describes the maintenance of equal absolute rate of oxygen delivery for metabolism in extreme environments as in normothermic, normoxic conditions. This is typically achieved by reducing basal heat stored, increasing heat dissipation, maintaining central blood volume, and increasing the relative oxygen carrying capacity of the blood. These cross acclimation adaptations reduce the increases in the relative cost of metabolism at a given workload under environmental stress. Cross tolerance describes cytoprotective adaptations that become acutely, and chronically induced given repeated environmental stimuli. Cross tolerance is largely facilitated by changes in basal heat shock proteins. Heat shock proteins are molecular chaperones which increase cellular resistance to apoptosis and maintain cellular and molecular function, for instance, the cascade of adaptation which follow changes in gene expression.

The primary aim of this project was to determine whether heat acclimation, an intervention typically implemented to prepare individuals for exercise in hot, humid conditions, would also prepare individuals for exposure to altitude (hypoxic) environments. This is a process known as cross acclimation.

Prior to determining the effectiveness of cross acclimation at a cellular and physiological levels, the heat acclimation process was refined with a series of experiments to determine the most effective way of implementing the intervention to induce the maximal magnitude of adaptation.

The primary finding from this project was that implementing a long term heat acclimation invention reduced physiological strain (Figure 1) when resting and exercising in hypoxia. In addition, the cellular stress response (characterised by Hsp72 mRNA) reduced in comparison to pre-intervention testing (Figure 2), and in comparison to participants who performed equivalent training in a cool environment (Figure 3).

Additionally, data arising from that project observed that the physiological and cellular responses to heat acclimation can be made more efficient via the implementation of an isothermic heat acclimation protocol (rather than a fixed intensity protocol), whereby a very hot, humid environment is combined with high initial workloads to rapidly increase core temperature. This provides the optimal stimuli for inducing physiological adaptation and cellular responses to the heat stress.

Gibson, O.R. Watt, P.W. Maxwell, N.S. Taylor L. (2016b) Hsp72 and Hsp90α mRNA transcription is characterised by large, sustained changes in core temperature during heat acclimation. Cell Stress and Chaperones (Awaiting DOI).

Gibson O.R. Willmott, A.G.B. James, C.A. Watt, P.W. Maxwell, N.S. (2016a) Setting the Correct Exercise Intensity to Optimise Isothermic Heat Acclimation. Journal of Strength and Conditioning Research (Awaiting DOI).

Gibson, O.R. Turner, G. Tuttle, J.A. Pringle, J.S.M. Taylor L. Watt, P.W. Maxwell, N.S. (2015c). Heat Acclimation attenuates the physiological and the Hsp72, but not Hsp90α mRNA response to acute normobaric hypoxia. Journal of Applied Physiology 119(8):889-99.

Gibson, O.R. Mee, J.A. Tuttle, J.A. Taylor L. Watt, P.W. Maxwell, N.S. (2015b) Isothermic and fixed intensity heat acclimation methods elicit equal increases in Hsp72 mRNA. Scandinavian Journal of Medicine and Science in Sports 25:259–268.

Gibson, O.R. Mee, J.A. Tuttle, J.A. Taylor L. Watt, P.W. Maxwell, N.S. (2015a) Isothermic and fixed intensity heat acclimation methods are similarly effective in heat adaptation following short and long term timescales. Journal of Thermal Biology 49-50, 55–65.

Gibson, O.R. Dennis, A. Parfitt, T. Taylor L. Watt, P.W. Maxwell, N.S. (2014) Extracellular Hsp72 concentration relates to a critical internal temperature during acute exercise-heat exposure. Cell Stress and Chaperones. 19 (3) 389-400

Conference Proceedings

Gibson, O.R. (2016) Heat vs hypoxic acclimation to improve physiological responses in a hypoxic environment. In symposium “Adaptation and Cross Tolerance to Environmental Stressors: From the Patient to the Athlete” at 6th International Conference on the Physiology and Pharmacology of Temperature Regulation (PPTR) 5-9 December, 2016. Ljubljana, Slovenia.

Gibson, O.R. Taylor, L. Watt, P.W. Maxwell, N.S. (2016) Hsp72 mRNA transcription, and Sweat Adaptations are greater post Heat Acclimation in Trained vs. Untrained individuals. In European Conference of Sport Sciences, Vienna, Austria. 5-9 July, 2016.

Gibson, O.R. Watt, P.W. Maxwell, N.S. (2015) Prescribing workload administration to optimise isothermic heat acclimation. The 16th International Conference on Environmental Ergonomics (ICEE). Portsmouth, UK. 28 June - 3July 2015.

Gibson, O.R. Turner, G. Watt, P.W. Maxwell, N.S. (2015) Heat acclimation attenuates physiological strain in acute normobaric hypoxia. In European Conference of Sport Sciences, Malmo, Sweden. 24-27 June 2015.

Gibson, O.R. Mee, J.A. Tuttle, J.A Taylor, L. Maxwell, N.S. Watt, P.W.(2014) Isothermic heat acclimation requires lower exercise durations to elicit superior adaptation to heat stress compared to a fixed intensity protocol. In. Aspetar Heat 2014: Training and Competing in the Heat. 23-24 March 2014.

Gibson, O.R. Dennis, A. Watt, P.W. Maxwell, N.M. (2012) Effect of Acute Heat-Exercise Exposure on eHSP70. In. ICSEMIS (International Convention on Science, Education and Medicine in Sport) Annual Conference. Glasgow. 19-24 July 2012.