What email address or phone number would you like to use to sign in to Docs.com?
If you already have an account that you use with Office or other Microsoft services, enter it here.
Or sign in with:
Signing in allows you to download and like content, and it provides the authors analytical data about your interactions with their content.
Embed code for: Periard_Cardiovascular adaptation
Select a size
Review Cardiovascular adaptations supporting human exercise-heat acclimation Julien D. Périard a,⁎, Gavin J.S. Travers a,b, Sébastien Racinais a, Michael N. Sawka c a Athlete Health and Performance Research Centre, Aspetar Orthopaedic and Sports Medicine Hospital, Doha, Qatar b Department of Life Sciences, Centre for Sports Medicine and Human Performance, Division of Sport, Health and Exercise Sciences, Brunel University London, Uxbridge, UK c School of Applied Physiology, Georgia Institute of Technology, Atlanta, GA, United States abstracta r t i c l e i n f o Article history: Received 15 October 2015 Received in revised form 29 January 2016 Accepted 4 February 2016 This review examines the cardiovascular adaptations along with total body water and plasma volume adjustments that occur in parallel with improved heat loss responses during exercise-heat acclimation. The cardiovascular system is well recognized as an important contributor to exercise-heat acclimation that acts to minimize physiological strain, reduce the risk of serious heat illness and better sustain exercise capacity. The upright posture adopted by humans during most physical activities and the large skin surface area contribute to the circulatory and blood pressure regulation challenge of simultaneously supporting skeletal muscle blood ﬂowanddissipatingheatviaincreasedskinbloodﬂowandsweatsecretionduringexercise-heatstress.Although it was traditionally held that cardiac output increased during exercise-heat stress to primarily support elevated skin blood ﬂow requirements, recent evidence suggests that temperature-sensitive mechanisms may also mediate an elevation in skeletal muscle blood ﬂow. The cardiovascular adaptations supporting this challenge include an increase intotal body water, plasma volumeexpansion, better sustainment and/or elevation of stroke volume, reduction in heart rate,improvement in ventricularﬁlling and myocardial efﬁciency, and enhanced skin blood ﬂow and sweating responses. The magnitude of these adaptations is variable and dependent on several factors such as exercise intensity, duration of exposure, frequency and total number of exposures, as well as the environmental conditions (i.e. dry or humid heat) in which acclimation occurs. © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Keywords: Blood pressure regulation Cardiac output Exercise performance Fluid balance Heat acclimatization Stroke volume Thermoregulation Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 2. Adaptation to heat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3. Total body water and blood (plasma) volume . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 4. Fluid balance and dehydration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 5. Cardiovascular adaptations to heat acclimation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 6. Aerobic exercise performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 7. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 1. Introduction It is well established that cardiovascular strain contributes to impair aerobic exercise performance in the heat (Rowell, 1974; Cheuvront et al., 2010; Nybo et al., 2014) and that cardiovascular adaptations are important contributors to the improved exercise capacity and reduced risk of serious heat illness conferred by exercise-heat acclimation (Sawka et al., 2011). Early physiologists recognized that a reduction in the elevated heart rate from heat stress likely was an important marker of adaptation to hot climates (Sundstroem, 1927). Lee and Scott (1916) were amongtheﬁrst toappreciatethatthe cardiovascular system likely imposed a physiological limitation to exercise performance under heat stress by “drafting blood away from the brain and the muscles to the skin”. Subsequently, Hill and Campbell (1922) demonstrated that Autonomic Neuroscience: Basic and Clinical 196 (2016) 52–62 ⁎ Corresponding author at: Athlete Health and Performance Research Centre, Aspetar Orthopaedic and Sports Medicine Hospital, PO Box 29222, Doha, Qatar. E-mail address: email@example.com (J.D. Périard). http://dx.doi.org/10.1016/j.autneu.2016.02.002 1566-0702/© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Contents lists available at ScienceDirect Autonomic Neuroscience: Basic and Clinical journal homepage: www.elsevier.com/locate/autneu improved evaporative cooling of the skin reduces cardiovascular strain and “keeps off fatigue” during exercise-heat stress. Perhaps the most important modern contributions regarding cardiovascular control with heat stress were made by Rowell (1974); Rowell et al. (1996) and Johnson (1977); Johnson et al. (2014), and integrated adjustments in such controls are critical to human heat acclimation (Taylor, 2014; Périard et al., 2015a). This review examines the cardiovascular adapta- tions along with total body water and plasma volume adjustments that occur in parallel with improved heat loss responses during exercise-heatacclimation.Thesephysiologicaladaptations/adjustments are critical to exercise-heat acclimation as upright posture, increased cutaneous vasodilation and greater sweat secretion provide severe challengestobloodpressureregulation,performance,andhealthduring exercise hot conditions. 2. Adaptation to heat When humans are repeatedly exposed to conditions that are sufﬁciently stressful to elicit profuse sweating and elevate skin and core temperature, adaptations develop that reduce the deleterious effects of heat stress: heat acclimation or acclimatization. Heat acclima- tion refers to repeated periods of heat exposure undertaken in artiﬁcial or laboratory settings, whereas heat acclimatization results from expo- sure to natural environments. Although both natural and artiﬁcial hot environments elicit similar physiological adaptations (Armstrong and Pandolf, 1988; Wenger, 1988), heat acclimatization provides more speciﬁc responses due to exposure to the exact conditions that will be encountered during work or competition (i.e. exercise task, solar radiationandterrain/geography)(Périardetal.,2015a).Thephenotypic adaptations that develop during repeated exposure to hot conditions improve performance during submaximal exercise, increase maximal aerobic capacity ( _VO2max) (Sawka et al., 1985; Lorenzo et al., 2010) and enhance thermal comfort (Lemaire, 1960; Folk, 1974; Gonzalez and Gagge, 1976) in the heat. These beneﬁts are achieved through plasma volume expansion, better maintenance of ﬂuid balance, enhanced sweating and cutaneous blood ﬂow responses, lowered exercising metabolic rate, and acquired thermal tolerance through the heat shock response, all of which contribute to improved cardiovascular stability and exercise performance during heat stress (Wyndham et al., 1976; Hori, 1995; Sawka et al., 1996; Horowitz, 2014; Périard et al., 2015a). Physiological adaptations related to repeated heat exposure develop relatively quickly with 75–80% of the acclimation process occurring in the ﬁrst 4–7 days (Fig. 1)(Pandolf, 1998; Shapiro et al., 1998). These adaptations can be categorized into short-term (b7 days), medium-term (8–14 days) and long-term acclimation (N15 days) (Garrett et al., 2011). Horowitz et al. (1993, 1996, 1998) argue that heat acclimation develops as a continuum of processes and have proposed a conceptual model characterized by a distinct biphasic pattern. The initial short-term phase is transient and manifested by a decreased effector organ output-to-autonomic signal ratio, such that accelerated efferent activity is required to override the subopti- mal peripheral responsiveness and produce adequate effector out- put. The second long-term phase is stable and characterized by an increased effector organ output-to-autonomic signal ratio, as both central and peripheral adaptations enhance physiological efﬁciency and reduce the need for accelerated excitation. Although passive heat exposure induces adaptations commensu- rate with that magnitude of strain (Takamata et al., 2001; Beaudin et al., 2009; Brazaitis and Skurvydas, 2010) and passive hot water immersion after exercise can improve endurance performance in the heat (Zurawlew et al., 2015), the inclusion of exercise with heat ex- posure provides additional strain that generally elicits more profound adaptations (Armstrong and Pandolf, 1988; Wenger, 1988). According- ly, the magnitude of physiological adaptation induced by heat acclima- tion or acclimatization depends largely on the initial heat exposure status (i.e. recentheatexposure, season,ﬁtnesslevel),aswell asthe ex- ercise intensity, duration, frequency, and number of heat exposures, along with the induction protocol (Sawka et al., 1996; Taylor, 2000; Taylor, 2014; Périard et al., 2015a). Repeated exercise-heat exposure at a constant work rate (i.e. traditional occupational and military heat acclimation protocol) is not likely as effective in eliciting adaptation as maintaining hyperther- mia at a given core temperature (e.g. 38.5 °C; controlled hyperthermia or isothermic heat acclimation) (Taylor, 2000, 2014). Indeed, the traditional heat acclimation model offers a constant forcing function (i.e. ﬁxed endogenous and exogenous thermal loads), which as adapta- tions progressively develop, results in decreased physiological strain and reduced further adaptations (Eichna et al., 1950; Fox et al., 1963a; Rowelletal.,1967).Incontrast,withcontrolledhyperthermia protocols the forcing function is increased in proportion to the adaptations by manipulating the endogenous and/or exogenous thermal loads (Garrett et al., 2011; Taylor, 2014). Therefore, it is suggested that greater physiological adaptations occur during a given period with controlled hyperthermia than traditional approaches. Interestingly, re- cent studies have not found greater adaptations with controlled hyper- thermia and the explanation for those ﬁndings are unclear (Gibson et al., 2015a,b). The similar adaptations between some traditional and controlled hyperthermia approaches may stem in part from different acclimation protocols inducing distinctive autonomic responses that result in Fig.1.Thetimecourseofadaptationstoexercise-heatacclimation.Withinaweekofacclimationplasmavolumeexpansionoccursandheartrateisreducedduringexerciseatagivenwork rate. Core and skin temperatures are also reduced when exercisingat a given work rate, whereassweat rate increases. Perceptually,the rating of thermal comfort isimproved. Asa result, aerobic exercise capacity is increased. Of note, the magnitude of these adaptations is dependent on the initial state of acclimation and the acclimation protocol (e.g. environmental conditions and exercise intensity). Adapted with permission from Périard et al. (2015a). 53J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52 –62 comparable physiological adjustments. For example, Moran et al. (1996) demonstrated in rats that both heat acclimation and exercise training improve cardiac efﬁciency (i.e. decreased rate pressure product: heart rate × systolic blood pressure) during exercise in the heat; however this was achieved via different pathways. Heat acclimation attenuated the increase in blood pressure, whereas exer- cise training had a more pronounced effect on heart rate during ex- ercise in the heat (Moran et al., 1996). In humans, a controlled exercise intensity heat acclimation protocol has recently been suggested whereby maintaining a given level of cardiovascular strain during daily exercise-heat exposure may optimize adaptations (Périard et al., 2015a). The level of strain achieved and sustained in this protocol would correspond to the heart rate associated with a speciﬁc relative exercise intensity (e.g. percent _VO2max, ventilatory or lactate threshold) in cool conditions. This heart rate would be sustained during exercise in the heat by increasing the power output accordingly as the individual adapted. Consequently, absolute work rate would increase as acclima- tion developed, thus providing a constant cardiovascular stimulus, based on the level of strain targeted. The physiological adaptations associated with heat acclimation are transientandgraduallydisappearifconsistentheatexposureisnotmain- tained. The adaptations that develop most rapidly (e.g. improvements in heart rate) during acclimation are also those that are lost most quickly (Williams et al., 1967; Pandolf et al., 1977). Currently, there is no agree- ment concerning the rate of decay for heat acclimation. For example, it has been suggested that one day of exercise in the heat is required for every 5 days spent without heat exposure to maintain adaptation (Pandolf et al., 1977; Taylor, 2000), while others have proposed that one day of acclimation is lost for every 2 days spent without heat exposure(GivoniandGoldman,1972).Notwithstanding,thereissupport for the notion that aerobic ﬁtness and regular exercise are critical during the decay period in providing stimulus for maintaining the achieved adaptations (Pandolf et al., 1977; Weller et al., 2007). 3. Total body water and blood (plasma) volume The fraction of mass represented by water in the human body is ~60%. This fraction varies in relation to body composition however, suchthattotalbodywaterestimationsaregenerallycalculatedasacon- stant fraction of fat-free mass with a factor of ~0.737 (Wang et al., 1999). During the ﬁrst week of heat acclimation, total body water gen- erally increases by 2–3 L (~5–7%) (Bass et al., 1955; Wyndham et al., 1968; Patterson et al., 2004a, 2014). This increase is divided between extracellular (plasma and interstitial ﬂuid) and intracellular ﬂuid com- partments. The division of the total body water increase between com- partments is variable, with studies reporting that extracellular ﬂuid accounts for greater, equal and smaller than its percentage increase in total body water after heat acclimation (Sawka and Coyle, 1999). Fig. 2 provides body ﬂuid compartment values before, during (day 8) and after (day 22) exercise-heat acclimation (Patterson et al., 2004a). Total body water, extracellular and intracellular ﬂuid volumes and plasma volume were expanded either during or after exercise heat acclimation. The increase in total body water during heat acclima- tion was likely due to the large aldosterone and arginine vasopressin secretion occurring during exercise-heat stress (Francesconi, 1988), withbloodandplasmaconcentrationsincreasingby200–300%afterex- ercise in both hot-dry and hot-wet environments, relative to resting values (Francesconi et al., 1983; Nielsen et al., 1993; Nielsen et al., 1997). A further pathway modulating the increase in total body water lies with the conservation of sodium that occurs with heat acclimation, which also helps maintain the number of osmoles in the extracellular ﬂuid, and thus to conserve or increase extracellularﬂuid volume during adaptation (Nose et al., 1988). Acutely, plasma volume expansion occurs after 3–4 days of heat exposure (Senay et al., 1976; Sawka and Coyle, 1999). The expansion typically varies between 4 and 15%, but can range from 3 to 27% (Bass et al., 1955; Senay et al., 1976; Nielsen et al., 1993; Patterson et al., 2004a, 2014; Karlsen et al., 2015a), with erythrocyte volume remaining unaltered (Sawka and Young, 2000). Typically, the greatest expansion of plasmavolume is observed on abouttheﬁfthdayof exercise-heatac- climation in fully hydrated individuals. Previous studies have described the rapid increase in plasma volume as being a transient phenomenon, with a small contraction occurring from this expanded state after one week of acclimation (Fig. 1)(Wyndham et al., 1968; Senay, 1979; Shapiro et al., 1981). More recently however, it has been suggested that this phenomenon may have been an experimental artifact stem- ming from to the traditional constant work rate model of heat acclima- tion. It would appear that by using the controlled hyperthermia approach, which maintains a constant adaptation stimulus by clamping core temperature (e.g. 38.5 °C) throughout acclimation, plasma volume remains expanded (~14%) for a sustained period (8–22 days) of heat exposure (Fig. 2)(Patterson et al., 2004a, 2014). The pathways via which the increase in plasma volume may be maintained include the oncotic effect of a net increase in total intravascular protein content during heat acclimation, which causes a movement of ﬂuid from the interstitial to the intravascular space (Senay et al., 1976; Senay, 1979; Harrison et al., 1981). The increase in Fig.2.Resting total body water (TBW), plasma volume (PV), red cell volume (RCV),extracellularﬂuid(ECF),interstitialﬂuid (ISF) and intracellularﬂuid (ICF) prior to and during a three-week heat acclimation regimen. Upper panels n = 12, lower panels n = 8 (mean ± SEM). *Signiﬁcantly different from Day 1 (P b 0.05). Reprinted with permission from Patterson et al. (2004a). 54 J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52–62 intravascular protein content is purported to stem in part from increased de novo albumin synthesis (Horowitz and Adler, 1983; Yang et al., 1998), a reduction in protein loss through the cutaneous capillaries in response to an acclimation-induced decrease in skin blood ﬂow (Harrison, 1985), as well as a reduction in the permeability of cutaneous capillaries to large molecules, wherein protein remain within the intravascular space (Senay, 1970, 1972); adaptations which in turn support plasma volume expansion. The maintenance of plasma volume expansion is also associated with an increase in extracellular ﬂuid, mediated by the retention of crystalloids, primarily sodium chloride (Mack and Nadel, 1996; Patterson et al., 2004a, 2014). Theretentionofplasmavolumeexpansionduringchronicheataccli- mation is in contrast to the acute effect of plasma volume expansion. Using a hyperoncotic 25% albumin solution or 0.9% saline, Hubbard et al. (1984) demonstrated that plasma volume was acutely expanded for 9–12 h in both hot and temperate conditions, but by a greater magnitude under heat stress. The authors further demonstrated a re- turn in plasma volume to near baseline values by 24 h post-infusion, which is suggestive of a circadian pattern of plasma volume expansion and contraction. Interestingly, it was noted that after albumin infusion, heat exposure signiﬁcantly increased plasma volume compared with saline and appeared to extend the retention time of the infused albumin, resulting in a more prolonged increase in oncotic pressure (Hubbardetal.,1984).Althoughdebateremainsastowhatlevelplasma volumecanbeexpandedandwhetherornotthisexpansionissustained duringheatacclimation,anincreaseinplasmavolumedoesprovidetwo major physiological advantages: i) increasing vascular ﬁlling pressure to support cardiovascular stability (i.e. increased stroke volume and arterial blood pressure) (Senay et al., 1976), and ii) increasing the speciﬁc heat of blood (Blake et al., 2000), thus improving heat transfer from the core to the skin and theoretically allowing slightly lower cutaneous blood ﬂow responses (Sawka et al., 2011). Fig. 3 provides the relation between the percent changes in heart rate at the end of exercise (4 h) to the percent change in plasma volume after 10 days of humid heat acclimation, relative to the ﬁrst day of heat exposure (Senay et al., 1976). These data suggest that plasma volume expansion, and thus perhaps improved cardiac ﬁlling, contribute to the reduced heartrateresponseduringheatacclimation.Thisissimilartotheexpan- sion of blood volume (i.e. plasma and erythrocyte) that occurs during aerobic training and which is considered an important contributor to improvements in endurance performance by allowing for greater ventricular ﬁlling and a consequent larger stroke volume (Hellsten and Nyberg, 2016). 4. Fluid balance and dehydration Thirst during exercise-heat stress has historically not been consid- ered a good indicator of body water needs since ad libitum water con- sumption often resulted in incomplete ﬂuid replacement, or voluntary dehydration (Adolph and Dill, 1938; Bean and Eichna, 1943; Eichna et al., 1945; Adolph, 1947; Greenleaf and Sargeant, 1965; Greenleaf et al., 1983; Armstrong et al., 1985; Greenleaf, 1992). Drinking behavior and ﬂuid replacement are processes inﬂuenced by physiological, psychological and environmental factors, as well as issues related to ﬂuid palatability, food intake, and gastric distension/discomfort (Ormerod et al., 2003). The mechanisms via which drinking and ﬂuid replacement are regulated during and following exercise include a sodium ion-osmotic-vasopressin pathway (Andersson et al., 1980) and a renin-angiotensin II-aldosterone pathway (Fitzsimons, 1979). It is suggested that thirst sensations occur in response to changes in plasma osmolality, plasma volume, and angiotensin II (Fitzsimons, 1979; Epstein, 1982; Rolls and Rolls, 1982). Heat acclimation improves the relationship of thirst to body water needs by a reducing the time to ﬁrst drink, increasingthe number of drinks consumed per heat expo- sure, and increasing mean volume per drink (Greenleaf et al., 1983; Hubbard et al., 1990), such that voluntary dehydration is markedly reduced (~30%) (Bean and Eichna, 1943; Eichna et al., 1945; Eichna et al., 1950). Fig. 4 plots the difference between ad libitum water intake and water loss during 6 days of humid heat acclimation (Eichna et al., 1945). Note that after three days water deﬁcits were reduced by 50%. Thus, heat acclimated individuals are better able to maintain hydration status during exercise-heat stress and minimize body water losses, provided access to ﬂuids is not restricted. Another important adaptation from heat acclimation to defend extracellular volume, and thus plasma volume, is improved sodium reabsorption in the eccrine sweat gland (Quinton, 2007). Indeed, an unacclimated person may secrete sweat with a sodium concentration of 60 mEq/L or higher, and therefore if sweating profusely can lose large amounts of sodium (Allan and Wilson, 1971). With heat accli- mation, eccrine sweat glands increase sodium reabsorption along the duct, which can reduce sweat sodium concentrations to as low as 10 mEq/L. Fig. 5 demonstrates the relationship of sweat sodium concentration and sweating rate before and after heat acclimation (Allan and Wilson, 1971). As indicated, sweat sodium concentration is signiﬁcantly reduced for a given sweat rate following acclimation. Fig. 3. Percent changes in heart rate relative to percent changes in plasma volume at the end of 4 h of exercise following 10 days of heat acclimation. Values from the ﬁrst day of heat exposure were taken as control values. Redrawn with permission from Senay et al. (1976). Fig. 4. Difference between ad libitum water intake and water loss in 15 men during work in humid heat over a 6-day period, compared with work in a cool environment (Eichna et al., 1945). Redrawn with permission from Sawka et al. (1984). 55J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52 –62 Dehydration, or a reduction in total body water and plasma volume, is known to adversely increase cardiovascular strain and im- pair aerobic performance during exercise-heat stress (Adolph, 1947; Morimoto, 1990; Sawka and Coyle, 1999; Sawka et al., 2015). The deleterious cardiovascular effects of dehydration are characterized by difﬁculty to sustain blood pressure and cardiac output, and a potential reduction in skeletal muscle blood ﬂow during exercise- heat stress (Sawka and Coyle, 1999; Sawka et al., 2011; Nybo et al., 2014; Sawka et al., 2015). As shown in Fig. 6, combining dehydration with exercise-heat stress results in reduced cardiac output and skeletal muscle blood ﬂow, compared to when euhydrated (Gonzalez-Alonso et al., 1998). Drinking sufﬁcientﬂuids to minimize dehydration duringheat acclimation should therefore help to sustain cardiac output and perhaps skeletal muscle blood ﬂow, and thus optimize exercise capacity under heat stress. Adaptations in sweat rate were among the ﬁrst described in response to heat acclimatization. Indeed, by the end of the 1940's it was widely accepted that heat acclimatization increases sweating capacity (Dill et al., 1933; Adolph and Dill, 1938; Dill et al., 1938; Robinson et al., 1943; Horvath and Shelley, 1946). Along with a shift in the onset threshold for sweating, which occurs earlier and at a lower core temperature, almost exact parallel improvements are noted in skin blood ﬂow (Nadel et al., 1974; Roberts et al., 1977). These sweat and skin blood ﬂow responses are indicative of central and peripheral adaptations (Nadel et al., 1971), which are depicted in Fig. 7. At the central level, heat acclimation decreases the body temper- ature at which thermoregulatory sweating and skin vasodilation are initiated. This adjustment in onset threshold is proposed to correspond to an absolute change in mean body temperature, rather than to the attainment of a predetermined mean body temperature (Patterson et al., 2004b). Peripheral adaptations, manifested by changes in sweat rate and sensitivity, occur at the level of the sweat glands (Fox et al., 1964; Chen and Elizondo, 1974; Inoue et al., 1999; Buono et al., 2009a; Buono et al., 2009b), which become resistant to fatigue so that higher sweat rates can be sustained, particularly in humid climates (Fig. 8) (Gonzalez et al., 1974). These adaptations include improved cholinergic sensitivity,andincreasedsizeandefﬁciencyofeccrineglandsinproduc- ing sweat per unit length of secretory coil (Sato and Sato, 1983; Sato et al., 1990). Peripheral factors contributing to improved sweating and skin blood ﬂow responses likely include an increase in the number and sensitivity of muscarinic receptors, a decrease in cholinesterase activity that potentiates and prolongs acetylcholine concentration in the cholinergic neural junction, which improves the vascular response to a given acetylcholine level, or alterations to the pathway of vasodilation within smooth muscles or the endothelial cells (Lorenzo and Minson, 2010). 5. Cardiovascular adaptations to heat acclimation The primary cardiovascular challenge during exercise in the heat is to provide sufﬁcient cardiac output to adequately perfuse skeletal muscle to support metabolism, while simultaneously perfusing skin to support heat loss. The traditional belief was that skeletal muscle blood ﬂow is not altered by heat stress and that increases in cardiac output support elevated skin blood ﬂow requirements (Rowell, 1974; Johnson, 1977). Recent studies however, show that elevated tissue/blood temperatures induce an increase in skeletal muscle Fig. 5. Sweat sodium concentration in relation to sweat rate in the unacclimated and acclimated state. Adapted with permission from Allan and Wilson (1971). Fig. 6. Cardiac output and blood ﬂows during dehydration and control trials. A: cardiac output, B: 2-legged blood ﬂow, C: non-exercising tissue blood ﬂow, D: forearm blood ﬂow. Filled squares represent dehydration and open squares represent control. *Signiﬁcantly lower than 20 min value (P b 0.05). †Signiﬁcantly lower than control (P b 0.05). Reprinted with permission from Gonzalez-Alonso et al. (1998). 56 J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52–62 blood ﬂow during rest and exercise (Pearson et al., 2011; Chiesa et al., 2015; Gonzalez-Alonso et al., 2015). The mechanisms medi- ating this increase may include an interaction of metabolic and thermal stimuli inducing the release of erythrocyte-derived ATP, a potent vasodilator (Gonzalez-Alonso et al., 2015). Thus, it may be postulated that in unacclimatized individuals higher body/tis- sue temperatures would induce greater skeletal muscle blood ﬂow requirements, and that with heat acclimation these require- ments might decline with lower body/tissue temperatures during exercise-heat stress. These metabolic and thermoregulatory demands are generally viewed as competing, whereby cardiac function is altered, the distribu- tionof cardiac output is modiﬁed, and/or the ability to sustain adequate blood pressure is compromised (Rowell, 1986; Sawka et al., 2011). Alternatively, the conﬂict between regulatory systems may be viewed as commensalism: an integrated balance of regulatory control where one circulation beneﬁts without substantially affecting the other (Kenney et al., 2014). Notwithstanding, heat acclimation improves the ability to sustain cardiac output during exercise-heat stress. Fig. 9 provides an example of this improvement with cardiac output, stroke volume and leg blood ﬂow responses during exercise to exhaustion in a hot-dry environment before and after heat acclimation (Nielsen et al., 1993). Notably, heat acclimation improved the ability to perform endurance exercise in the heat. This was accompanied by lowered heart rate, increased stroke volume and sustained leg blood ﬂow, and sustained or improved cardiac output responses. The effects of heat acclimation on stroke volume and cardiac output duringexercise-heat stress depend largely on exercise intensity, as well as the type and severity of the heat stress. For example, two studies in which low to moderate work was conducted in the heat reported in- creases in stroke volume with little change in cardiac output as heart rate decreased with acclimation (Rowell et al., 1967; Wyndham et al., 1968). Another study reported a decrease in cardiac output in associa- tionwithareductionincutaneousbloodﬂow,butlittlechangeinstroke volume as heart rate decreased, again during work performed in hot conditions (Wyndham, 1951). A separate study reported a mixed pat- tern, with two subjects showing a steady increase in stroke volume, one a transient increase reversing after the sixth day, and one showing no increase with heat acclimation (Wyndham et al., 1976). The reason Fig. 7. Schematic representation of the central and peripheral adaptations that occur in response (Pre vs. Post) to heat acclimation (HA). The body core temperature threshold for the onset of sweating is reduced, while the rate and sensitivity (i.e. slope) are increased (Nadel et al., 1974; Roberts et al., 1977). Concomitantly, the body core temperature threshold for the onset of cutaneous vasodilation is reduced, whereas skin blood ﬂow sensitivity is increased (Fox et al., 1963b; Roberts et al., 1977; Yamazaki and Hamasaki, 2003; Lorenzo and Minson, 2010). Adapted from Nadel et al. (1974) and Werner (1994) and reprinted with permission from Périard et al. (2015a). Fig. 8. Improvements in sweating capacity on Days 1 and 6 of cycle ergometer exercise (25–30% _VO2max) in 40 °C air temperature and increasing humidity from a vapor pressure of 12 mmHg to 49 mmHg each day. Skin wettedness (w) is equal to skin evaporation (Esk)/maximum evaporative capacity (Emax). Adapted with permission from Gonzalez et al. (1974). Fig. 9. Cardiac output (Q), stroke volume (SV) and leg blood ﬂow (LBF) during exercise (10 and 40 min) and just before volitional exhaustion (Exh). Open hatching: before acclimation, Close hatching: after 9–12 days of acclimation. Before acclimation the 40 min values were those taken just before exhaustion (mean ± SEM). Number of measurements indicated. *Signiﬁcantly different from ﬁnal measurements before acclimation (P b 0.05). Reprinted with permission from Nielsen et al. (1993). 57J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52 –62 forthesedifferencesisunclear,althoughdifferencesinthemethodology to assess these parameters may account for some variation, while another possibility might relate to exercise being performed in dry heat (Rowell et al., 1967) versus humid heat (Wyndham, 1951; Wyndham et al., 1968, 1976). Nielsen et al. (1993, 1997) examined stroke volume responses dur- ing exercise (45–50%VO2max) before and after dry (40 °C, 10% relative humidity;RH)andhumid(35°C,87%RH)heatacclimation.Theauthors reported that during exercise, dry heat acclimation increased stroke volume (~21 mL/beat) and cardiac output (~1.8 L/min) (Nielsen et al., 1993), whereas humid heat acclimation did not inﬂuence either response (Nielsen et al., 1997), despite both studies reporting a plasma volumeexpansionof 9–13%. Others havealsoshownthat10days of dry heat acclimation improves maximal stroke volume and cardiac output during a _VO2max test in cool (13 °C), but not hot (38 °C) conditions, without inﬂuencing maximum heart rate (Lorenzo et al., 2010). Moreover, short-term moderate intensity (70% _VO2max, 30 min/day) exercise-heat acclimation in 30 °C and 50% RH has been shown to increase plasma volume and stroke volume, and decrease heart rate (Goto et al., 2010). Taken together, these observations indicate that heat acclimation improves central hemodynamics, but that the magni- tude of improvement may depend on the environmental condition (i.e. dry vs. humid heat), acclimation protocol (i.e. stimulus impulse), exercise intensity, and subject population. Hence, additional research is required to fully elucidate the impact of heat acclimation on central hemodynamic responses. The hallmark cardiovascular adaptations induced during heat acclimation include a lowering of heart rate and an increase in stroke volume, which support the maintenance of cardiac output and the regulation of blood pressure during submaximal exercise (Table 1). The lowering of heart rate and increased stroke volume are likely sup- ported by changes in myocardial autonomic tone. Autonomic adjust- ments during exercise are mediated by central command, cardiopulmonary and arterial baroreﬂexes, and carotid chemoreﬂexes (Fisher et al., 2015), all of which are further modiﬁed during exercise- heat stress (Nybo et al., 2014). Therefore, the net affect on parasympa- thetic/sympathetic efferent activity and thus myocardial chronotropic, inotropicandlusitropicpropertiesislikelyspeciﬁctotheexerciseinten- sity, hydration status, ﬁtness level, as well as heat acclimation status. With heat acclimation, it is anticipated that better tissue perfusion, re- ducing metaboreceptor stimulation; reduced metabolic lactate produc- tion, reducing carotid chemoreﬂex stimulation for respiratory compensation; improved cardiac ﬁlling and blood pressure regulation, reducing low and high pressure baroreceptor stimulation; and tissue (i.e. muscle and brain) temperatures, modifying central command; all contribute to alter cardiac autonomic regulation. A direct effect of temperature on cardiac pacemaker cells may also contribute to the lowering in heart rate during exercise at a given workload (Berlyne et al., 1974; Horowitz and Meiri, 1993). This heat acclimation-induced bradycardia may further relate to a decrease in overall thermal (i.e. lower core and skin temperatures) and concomi- tantly cardiovascular strain, and to alterations in total blood volume (Shapiro et al., 1998), which as discussed earlier may reduce both skin and skeletal muscle blood ﬂow requirements. The increase in plasma volume may serve to support greater venous return and cardiac preloading, leading to improved ventricularﬁlling and increased stroke volume (Senay, 1986). A rightward shift in the diastolic pressure‐vol- ume curve thus occurs, which allows for greater ventricular ﬁlling and augmented stroke volume without a change in pressure (Horowitz, 2003). Additionally, exercise-heat acclimated rats demonstrate in- creased left ventricular compliance and systolic pressure generation while myocardial _VO2 (i.e. the energetic cost of pumping) is lowered (Fig. 10)(Horowitz et al., 1986a,b; Levy et al., 1997). The reduced myocardial _VO2 is believed to be associated with myosin ATPase activity changes (Horowitz et al., 1986a). Globally, the adaptations are suggested to stem from concerted adjustments induced by exercise- heat acclimation that alter the mechanisms associated with the excita- tion–contraction coupling cascade, Ca2+ regulation, contractile and met- abolic responses (Horowitz et al., 1993; Horowitz, 2003; Kodesh et al., 2011).Althoughitremainstobedeterminedwhethersuchfunctionalad- aptations occur in humans, heat stress is known to reduce left ventricular pressure and increase left ventricular systolic function (Crandall et al., 2008; Brothers et al., 2009), such that following heat acclimation greater ventricular ﬁlling may occur at a lower ventricular pressures. Molecular adaptations at the level of the cardiac muscle also occur in response to the induction of heat shock proteins (Hsp), which were originally described for their role as molecular chaperones in maintaining cellular conformation and homeostasis (Locke, 1997; Kregel, 2002). The heat shock response induced during exposure to heat stress confers transient thermotolerance and protection against subsequent exposure, as well as cardioprotection (Horowitz and Assadi, 2010). Interestingly, exercise-heat acclimation appears to in- crease basal intracellular Hsp72 and Hsp90 levels, and blunt the acute response(i.e.inducibility)toexerciseintheheatasadaptationsdevelop (Amorim et al., 2015; Périard et al., 2015a). McClung et al. (2008) demonstrated in peripheral blood mononuclear cells that individuals demonstrating the greatest physiological adaptations exhibit the greatest blunting in ex vivo Hsp72 and Hsp90 inducibility. At the extra- cellularlevel, increases in thebasal expression of Hsp72 followingexer- cise are less consistent. Indeed, whilst similar increases in intracellular (i.e. monocyte) and extracellular Hsp72 expression occur immediately following exhaustive exercise in the heat, the extracellular expression Table 1 Adaptations in cardiovascular function associated with heat acclimation that lead to improved cardiovascular stability. Cardiovascular parameter Adaptation Heart rate Lowered Stroke volume Increased Cardiac output Better sustained Blood pressure Better sustained Myocardial compliance Increased Myocardial efﬁciency Increased Cardioprotection Improved Adapted with permission from Sawka et al. (2011). Fig. 10. Relationship between oxygen consumption and cardiac work (expressed as the rate-pressure product) in hearts of sedentary unacclimated (C) and heat acclimated (AC) rats for 1 month. Marked shift to the right of the regression line of heat-acclimated hearts compared with that of unacclimated hearts implies signiﬁcantly increased work efﬁciency of heat-acclimated hearts (P b 0.0007) (Levy et al., 1997). Reprinted with permission from Horowitz (1998). 58 J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52–62 decreases below basal (i.e. pre-exercise) levels 24 h after exercise (Périard et al., 2012), whereas intracellular levels increase (Périard et al., 2015b). 6. Aerobic exercise performance Heatacclimationcanhaveprofoundbeneﬁtsoncardiovascularfunc- tion and concomitantly aerobic performance in the heat. For example, Racinais et al. (2015) demonstrated that three cycling time trials (43 km) undertaken in hot outdoor conditions (~37 °C) were initiated at a similar power output to that of time trials conducted in cool condi- tions (~8 °C) (Fig. 11). However, a marked decrease in power output occurred in the heat following the onset of exercise, which was partly recovered after one week of training in the heat and almost fully restored after two weeks of training in the heat. As expected, heart rate was similar during all trials in the heat and slightly higher than in the cool, which supports the contention that a similar relative exercise intensity (i.e. % _VO2max) was maintained (Périard et al., 2011; Wingo et al., 2012; Périard and Racinais, 2015)andthatwithheatac- climation absolute intensity (i.e. power output) increased. Heat acclimation has been shown to improve the _VO2max of trained individuals in hot conditions with Sawka et al. (1985) reporting a 4% (49 °C) improvement and Lorenzo et al. (2010) and Keiser et al. (2015) noting increases of 8–10% (38 °C). Despite these improvements, acute heat stress mediates a reduction in _VO2max relative to values recorded in temperate conditions that cannot be compensated for by heat acclimation (i.e. _VO2max in the heat remains lower than in cool conditions). Notwithstanding, heat acclimation has been shown to in- crease cycle exercise time trial performance in the heat in conjunction withanincreaseincardiacoutputandlactatethreshold,plasma volume expansion, lower skin temperatures, and a larger core-to-skin gradient after heat acclimation (Lorenzo et al., 2010). Moreover, the increase in performance was proportional to the increase in _VO2max in the heat (Lorenzo et al., 2010), which further reinforces the notion that relative exercise intensity signiﬁcantly inﬂuences self-paced exercise perfor- mance in the heat (Périard et al., 2011; Périard and Racinais, 2015). Observationsofenhancedself-pacedexerciseperformancehavealso beennotedincoolconditionsinproportiontoimprovementsin _VO2max underthesameconditions(Lorenzoetal.,2010).Thissupportsprevious observations of heat acclimation increasing _VO2max in trained (3–5%) (Sawka et al., 1985; Lorenzo et al., 2010), untrained (13%) and unﬁt (23%)individualsincoolconditions(Shvartzetal.,1977),andreinforces the 32% increase in run time to exhaustion noted in ﬁt individuals after heat acclimation via post-exercise sauna bathing (Scoon et al., 2007). It also supports ﬁndings of team-sport athletes improving endurance performance(i.e.Yo-YoIntermittentRecoverytest)intemperatecondi- tions (~22 °C) following training camps in the heat (~34 °C) (Buchheit et al., 2011, 2013; Racinais et al., 2014). The pathways via which a transfer of adaptation between hot and cool conditions would increase performance might be linked to a variety of ergogenic responses, in- cluding cardiovascular, thermoregulatory and cellular adaptations (Lorenzo et al., 2010; Bruchim et al., 2014; Corbett et al., 2014). In con- trast, other investigations in which 5 days of isothermic (~38.6 °C) heat acclimation with permissive dehydration (Neal et al., 2015), 10 days of constant intensity (50% _VO2max heart rate) heat acclimation (Keiser et al., 2015), and 14 days of natural heat acclimatization (Karlsen et al., 2015b) were utilized, did not demonstrate an improvement in _ V O2max or time trial performance in cool conditions in trained cyclists. Clearly, this will become a controversial area and merit additional research with well-designed protocols to elucidate the mechanisms and possible transfer of ergogenic beneﬁts from heat acclimation towards improving aerobic performance in cooler conditions. Thereareseveraladditionalpotentialbeneﬁtsthatmaybeconferred by heat acclimation that could contribute to improved exercise capabil- ities. Heat acclimation can decrease the oxygen uptake response to submaximal exercise (Sawka et al., 1983, 1996). The greater reliance oncarbohydrateasa fuelsourceduringexerciseintheheatisalsoinﬂu- enced by heat acclimation (Young et al., 1985; Febbraio et al., 1994), with muscle glycogen utilization decreasing by 40–50% (King et al., 1985; Kirwan et al., 1987). This glycogen-sparingeffectof heat acclima- tion has also been shown to be quite small however, and apparent only duringexerciseincoolconditions(Youngetal.,1985).Afurthereffectof heat acclimation is thereduction of blood and muscle lactate accumula- tionduringsubmaximalexercise(Febbraioetal.,1994)andtheincrease in power output at lactate threshold (Lorenzo et al., 2010; Neal et al., 2015). The mechanisms mediating these adaptations remain unclear, but could stem from the increase in total body water enhancing lactate removal through increased splanchnic circulation (Rowell et al., 1968), or through increased cardiac output and decreased metabolic rate delaying lactate accumulation (Sawka et al., 1983; Young et al., 1985). 7. Summary Acuteheat stressimpairs aerobic exercisecapacityand elevated car- diovascular strain has long been considered an important contributor. Repeated heat exposure however, induces adaptations that abate car- diovascularstrainandlikelycontributetoattenuatetheexerciseperfor- mance impairment, and reduce the risk of serious heat illness. The cardiovascular adaptations supporting this include an increase in total body water, plasma volume expansion, better sustainment and/or elevation of stroke volume, reduction in heart rate, improvement in ventricular ﬁlling and myocardial efﬁciency, and enhanced skin blood ﬂow and sweating responses. The magnitude of these adaptations is dependent on several factors such as exercise intensity, duration, frequency and number of exposures to the heat, as well as to the environmental conditions (e.g. dry vs. humid heat) and protocol in which acclimation occurs. Acknowledgments The authors report no conﬂict of interest. No funding was received for this review. References Adolph, E.F., 1947. Physiology of Man in the Desert. Interscience, New York. Adolph, E.F., Dill, D.B., 1938. Observations on water metabolism in the desert. Am. J. Phys. 123, 369–378. Allan,J.R., Wilson, C.G., 1971. Inﬂuence of acclimatization on sweat sodiumconcentration. J. Appl. Physiol. 30, 708–712. Fig.11.Poweroutputduring43.4kmcyclingtimetrialsperformedinCool(~8°C;average oftrialsperformedbeforeandafterheatacclimatization)andHot(~37°C)conditionsafter one(Hot1),six(Hot2)andfourteen(Hot3)daysof trainingintheheat.*§†Cooltimetrial signiﬁcantly higher than TTH-1, TTH-2, and TTH-3, respectively (P b 0.05). Redrawn with permission from Racinais et al. (2015). 59J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52 –62 Amorim, F.T., Fonseca, I.T., Machado-Moreira, C.A., Magalhães, FdC, 2015. Insights into the role of heat shock proteins 72 to whole-body heat acclimation in humans. Temperature 00-00. Andersson, B., Olsson, K., Rundgren, M., 1980. ADH in regulation of blood osmolality and extracellular ﬂuid volume. J. Parenter. Enter. Nutr. 4288-96. Armstrong, L.E., Pandolf, K.B., 1988. Physical training, cardiorespiratory physical ﬁtness and exercise-heat tolerance. In: KB, Pandolf, MN, Sawka, RR, Gonzalez (Eds.), Human Performance Physiology and Environmental Medicine at Terrestrial Extremes. Benchmark Press, Indianapolis, IN, pp. 199–226. Armstrong, L.E., Hubbard, R.W., Szlyk, P.C., Matthew, W.T., Silsm, I.V., 1985. Voluntary dehydration and electrolyte losses during prolonged exercise in the heat. Aviat. Space Environ. Med. 56, 765–770. Bass, D.E., Kleeman, C.R., Quinn, M., Henschel, A., Hegnauer, A.H., 1955. Mechanisms of acclimatization to heat in man. Medicine 34, 323–380. Bean, W.B., Eichna, L.W., 1943. Performance in relation to environmental temperature. Reactions of normal young men to simulated desert environment. Fed. Proc. 2, 144–158. Beaudin, A.E., Clegg, M.E., Walsh, M.L., White, M.D., 2009. Adaptation of exercise ventila- tion during an actively-induced hyperthermia following passive heat acclimation. Am. J. Physiol. Regul. Integr. Comp Physiol. 297, R605–R614. Berlyne, G.M., Finberg, J.P., Yoran, C., 1974. The effect ofβ-adrenoceptor blockade on body temperature and plasma renin activity in heat-exposed man. Br. J. Clin. Pharmacol. 4, 307–312. Blake, A.S., Petley, G.W., Deakin, C.D., 2000. Effects of changes in packed cell volume on the speciﬁc heat capacity of blood: implications for studies measuring heat exchange in extracorporeal circuits. Br. J. Anaesth. 84, 28–32. Brazaitis, M., Skurvydas, A., 2010. Heat acclimation does not reduce the impact of hyperthermia on central fatigue. Eur. J. Appl. Physiol. 109, 771–778. Brothers, R.M., Bhella, P.S.,Shibata, S., Wingo, J.E.,Levine, B.D., Crandall, C.G., 2009. Cardiac systolic and diastolic function during whole body heat stress. Am. J. Physiol. Heart Circ. Physiol. 296, H1150–H1156. Bruchim, Y., Aroch, I., Eliav, A., Abbas, A., Frank, I., Kelmer, E., Codner, C., Segev, G., Epstein, Y., Horowitz, M., 2014. Two years of combined high-intensity physical training and heat acclimatization affect lymphocyte and serum HSP70 in purebred military working dogs. J. Appl. Physiol. (1985) 117, 112–118. Buchheit, M., Voss, S.C., Nybo, L., Mohr, M., Racinais, S., 2011. Physiological and perfor- mance adaptations to an in-season soccer camp in the heat: associations with heart rate and heart rate variability. Scand. J. Med. Sci. Sports 21, e477–e485. Buchheit, M., Racinais, S., Bilsborough, J., Hocking, J., Mendez-Villanueva, A., Bourdon, P.C., Voss, S., Livingston, S., Christian, R., Périard, J., Cordy, J., Coutts, A.J., 2013. Adding heat to the live-high train-low altitude model: a practical insight from professional football. Br. J. Sports Med. 47 (Suppl. 1), i59–i69. Buono, M.J., Martha, S.L., Heaney, J.H., 2009a. Peripheral sweat gland function is improved with humid heat acclimation. J. Therm. Biol. 34, 127–130. Buono, M.J., Numan, T.R., Claros, R.M., Brodine, S.K., Kolkhorst, F.W., 2009b. Is active sweating during heat acclimation required for improvements in peripheral sweat gland function? Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R1082–R1085. Chen, W.Y., Elizondo, R.S., 1974. Peripheral modiﬁcation of thermoregulatory function during heat acclimation. J. Appl. Physiol. 37, 367–373. Cheuvront, S.N., Keneﬁck, R.W., Montain, S.J., Sawka, M.N., 2010. Mechanisms of aerobic performance impairment with heat stress and dehydration. J. Appl. Physiol. (1985) 109, 1989–1995. Chiesa, S.T., Trangmar, S.J., Kalsi, K.K., Rakobowchuk, M., Banker, D.S., Lotlikar, M.D., Ali, L., Gonzalez-Alonso, J., 2015. Local temperature-sensitive mechanisms are important mediators of limb tissue hyperemia in the heat-stressed human at rest and during small muscle mass exercise. Am. J. Physiol. Heart Circ. Physiol. 309, H369–H380. Corbett, J., Neal, R.A., Lunt, H.C., Tipton, M.J., 2014. Adaptation to heat and exercise performance under cooler conditions: a new hot topic. Sports Med. 44, 1323–1331. Crandall, C.G., Wilson, T.E., Marving, J., Vogelsang, T.W., Kjaer, A., Hesse, B., Secher, N.H., 2008. Effects of passive heating on central blood volume and ventricular dimensions in humans. J. Physiol. 586, 293–301. Dill, D.B., Jones, B.F., Edwards, H.T., Oberg, S.A., 1933. Salt economy in extreme dry heat. J Biol. Chem. 100, 755–767. Dill, D.B., Hall, F.G., Edwards, H.T., 1938. Changes in composition of sweat during acclima- tization to heat. Am. J. Phys. 123, 412–419. Eichna, L.W., Bean, W.B., Ashe, W.F., Nelson, N.G., 1945. Performance in relation to environmental temperature. Reactions of normal young men to hot, humid (simulated jungle) environment. Bull. Johns Hopkins Hosp. 76, 25–58. Eichna, L.W., Park, C.R., Nelson, N., Horvath, S.M., Palmes, E.D., 1950. Thermal regulation dur- ing acclimatization in a hot, dry (desert type) environment. Am. J. Phys. 163, 585–597. Epstein, A.N., 1982. The physiology of thirst. In: DW, Pfaff (Ed.), The Physiological Mechanisms of Motivation. Springer-Verlag, New York, p. 164. Febbraio, M.A., Snow, R.J.,Hargreaves, M., Stathis, C.G., Martin, I.K., Carey,M.F., 1994. Mus- cle metabolism during exercise and heat stress in trained men: effect of acclimation. J. Appl. Physiol. 76, 589–597. Fisher, J.P., Young, C.N., Fadel, P.J., 2015. Autonomic adjustments to exercise in humans. Comp. Physiol. 5, 475–512. Fitzsimons,J.T.,1979.ThePhysiologyofThirstandSodiumAppetite.CambridgeUniversity Press, New York. Folk, G.E., 1974. Textbook of Environmental Physiology. Lea & Febiger, Philadelphia. Fox, R.H., Goldsmith, R., Kidd, D.J., Lewis, H.E., 1963a. Acclimatization to heat in man by controlled elevation of body temperature. J. Physiol. 166, 530–547. Fox, R.H., Goldsmith, R., Kidd, D.J., Lewis, H.E., 1963b. Blood ﬂow and other thermoregu- latory changes with acclimatization to heat. J. Physiol. 166, 548–562. Fox, R.H., Goldsmith, R., Hampton, I.F., Lewis, H.E., 1964. The nature of the increase in sweating capacity produced by heat acclimatization. J. Physiol. 171, 368–376. Francesconi, R.P., 1988. Endocrinological responses to exercise in stressful environments. Exerc. Sport Sci. Rev. 16, 235–284. Francesconi, R.P., Sawka, M.N., Pandolf, K.B., 1983. Hypohydration and heat acclimation: plasma renin and aldosterone during exercise. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 55, 1790–1794. Garrett, A.T., Rehrer, N.J., Patterson, M.J., 2011. Induction and decay of short-term heat acclimation in moderately and highly trained athletes. Sports Med. 41, 757–771. Gibson, O.R., Mee, J.A., Taylor, L., Tuttle, J.A., Watt, P.W., Maxwell, N.S., 2015a. Isothermic and ﬁxed-intensity heat acclimation methods elicit equal increases in Hsp72 mRNA. Scand. J. Med. Sci. Sports 25, 259–268. 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 induce similar heat adaptation following short and long-term timescales. J. Therm. Biol. 49-50, 55–65. Givoni, B., Goldman, R.F., 1972. Predicting rectal temperature response to work, environ- ment, and clothing. J. Appl. Physiol. 32, 812–822. Gonzalez, R.R., Gagge, A.P., 1976. Warm discomfort and associated thermoregulatory changes during dry, and humid-heat acclimatization. Isr. J. Med. Sci. 12, 804–807. Gonzalez, R.R., Pandolf, K.B., Gagge, A.P., 1974. Heat acclimation and decline in sweating during humidity transients. J. Appl. Physiol. 36, 419–425. Gonzalez-Alonso, J., Calbet, J.A.L., Nielsen, B., 1998. Muscle blood ﬂow is reduced with dehydration during prolonged exercise in humans. J. Physiol. 513, 895–905. Gonzalez-Alonso, J., Calbet, J.A., Boushel, R., Helge, J.W., Sondergaard, H., Munch-Andersen, T., van Hall, G., Mortensen, S.P., Secher, N., 2015.Blood temper- ature and perfusion to exercising and non-exercising human limbs. Exp. Physiol. 100, 1118–1131. Goto, M., Okazaki, K., Kamijo, Y., Ikegawa, S., Masuki, S., Miyagawa, K., Nose, H., 2010. Protein and carbohydrate supplementation during 5-day aerobic training enhanced plasma volume expansion and thermoregulatory adaptation in young men. J. Appl. Physiol. (1985) 109, 1247–1255. Greenleaf, J.E., 1992. Problem: thirst, drinking behavior, and involuntary dehydration. Med. Sci. Sports Exerc. 24, 645–656. Greenleaf, J.E., Sargeant, F.I., 1965. Voluntary dehydration in man. J. Appl Physiol. (1985) 20, 719–724. Greenleaf, J.E., Brock, P.J., Keil, L.C., Morse, J.T., 1983. Drinking and water balance during exercise and heat acclimation. J. Appl. Physiol. 54, 414–419. Harrison, M.H., 1985. Effects on thermal stress and exercise on blood volume in humans. Physiol. Rev. 65, 149–209. Harrison, M.H., Edwards, R.J., Graveney, M.J., Cochrane, L.A., Davies, J.A., 1981. Blood volume and plasma protein responses to heat acclimatization in humans. J. Appl. Physiol. 50, 597–604. Hellsten, Y., Nyberg, M., 2016. Cardiovascular adaptations to exercise training. Comput. Phys. 6, 1–32. Hill, L., Campbell, J., 1922. Cooling power of the atmosphere and comfort during work. J. Indust. Hyg. 4, 246–252. Hori, S., 1995. Adaptation to heat. Jpn. J. Physiol. 45, 921–946. Horowitz, M., 1998. Do cellular heat acclimation responses modulate central thermoregulatory activity? News Physiol. Sci. 13, 218–225. Horowitz, M., 2003. Matching the heart to heat-induced circulatory load: heat-acclimatory responses. News Physiol. Sci. 18, 215–221. Horowitz, M., 2014. Heat acclimation, epigenetics, and cytoprotection memory. Compr. Physiol. 4, 199–230. Horowitz, M., Adler, J.H., 1983. Plasma volume regulation during heat stress: albumin synthesis vs capillary permeability. A comparison between desert and non-desert species. Comp. Biochem. Physiol. A Comp. Physiol. 75, 105–110. Horowitz, M., Assadi, H., 2010. Heat acclimation-mediated cross-tolerance in cardioprotection: do HSP70 and HIF-1alpha play a role? Ann. N. Y. Acad. Sci. 1188, 199–206. Horowitz, M., Meiri, U., 1993. Central and peripheral contributions to control of heart rate during heat acclimation. Pﬂugers Arch. 422, 386–392. Horowitz, M., Peyser, Y.M., Muhlrad, A., 1986a. Alterations in cardiac myosin isoenzymes distribution as an adaptation to chronic environmental heat stress in the rat. J. Mol. Cell. Cardiol. 18, 511–515. Horowitz, M., Shimoni, Y., Parnes, S., Gotsman, M.S., Hasin, Y., 1986b. Heat acclimation: cardiac performance of isolated rat heart. J. Appl. Physiol. (1985) 60, 9–13. Horowitz, M., Parnes, S., Hasin, Y., 1993. Mechanical and metabolic performance of the rat heart: effects of combined stress of heat acclimation and swimming training. J. Basic Clin. Physiol. Pharmacol. 4, 139–156. Horowitz, M., Kaspler, P., Marmari, Y., Oron, Y., 1996. Evidence for contribution of effector organ cellular responses to the biphasic dynamics of heat acclimation.J.Appl. Physiol. 80, 77–85. Horvath, S.M., Shelley, W.B., 1946. Acclimatization to extreme heat and its effect on the ability to work in less severe environments. Am. J. Phys. 146, 336–343. Hubbard, R.W., Matthew, W.T., Horstman, D., Francesconi, R., Mager, M., Sawka, M.N., 1984. Albumin-induced plasma volume expansion: diurnal and temperature effects. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 56, 1361–1368. Hubbard, R.W., Szlyk, P.C., Armstrong, L.E., 1990. Inﬂuence of thirst and ﬂuid palatability on ﬂuid ingestion during exercise. In: CV, Gisolﬁ, DR, Lamb (Eds.), Perspectives in Exercise Science and Sports Medicine. Benchmark Press, Carmel, IN, p. 39. Inoue, Y., Havenith, G., Kenney, W.L., Loomis, J.L., Buskirk, E.R., 1999. Exercise- and methylcholine-induced sweating responses in older and younger men: effect of heat acclimation and aerobic ﬁtness. Int. J. Biometeorol. 42, 210–216. Johnson, J.M., 1977. Regulation of skin circulation during prolonged exercise. Ann. N. Y. Acad. Sci. 301, 195–212. Johnson, J.M., Minson, C.T., Kellogg, D.L., 2014. Cutaneous vasodilator and vasoconstrictor mechanisms in temperature regulation. Comput. Phys. 4, 33–89. 60 J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52–62 Karlsen, A., Nybo, L., Nørgaard, S.J., Jensen, M.V., Bonne, T., Racinais, S., 2015a. Time course of natural heat acclimatization in well-trained cyclists during a 2-week training camp in the heat. Scand. J. Med. Sci. Sports 25, 240–249. Karlsen, A., Racinais, S., Jensen, M.V., Nørgaard, S.J., Bonne, T., Nybo, L., 2015b. Heat acclimatization does not improve VO2max or cycling performance in a cool climate in trained cyclists. Scand. J. Med. Sci. Sports 25, 269–276. Keiser, S., Fluck, D., Huppin, F., Stravs, A., Hilty, M.P., Lundby, C., 2015. Heat training increases exercise capacity in hot but not in temperate conditions: a mechanistic counter-balanced cross-over study. Am. J. Physiol. Heart Circ. Physiol. (ajpheart 00138 02015). Kenney, W.L., Stanhewicz, A.E., Bruning, R.S., Alexander, L.M., 2014. Blood pressure regulation III: what happens when one system must serve two masters: temperature and pressure regulation? Eur. J. Appl. Physiol. 114, 467–479. King, D.S., Costill, D.L., Fink, W.J., Hargreaves, M., Fielding, R.A., 1985. Muscle metabolism during exercise in the heat in unacclimatized and acclimatized humans. J. Appl. Physiol. (1985) 59, 1350–1354. Kirwan, J.P., Costill, D.L., Kuipers, H., Burrell, M.J., Fink, W.J., Kovaleski, J.E., Fielding, R.A., 1987. Substrateutilizationinlegmuscleofmenafterheatacclimation.J.Appl.Physiol. (1985) 63, 31–35. Kodesh, E., Nesher, N., Simaan,A., Hochner,B., Beeri,R., Gilon,D., Stern,M.D., Gerstenblith, G., Horowitz, M., 2011. Heat acclimation and exercise training interact when combined in an overriding and trade-off manner: physiologic-genomic linkage. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R1786–R1797. Kregel, K.C., 2002. Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J. Appl. Physiol. (1985) 92, 2177–2186. Lee, F.S., Scott, E.L., 1916. The action of temperature and humidity on the working power of muscles and the sugar of the blood. Am. J. Phys. 40, 486–501. Lemaire,R., 1960.Considérationsphysiologiques sur laclimatisation enmilieudésertique. Journees d'Inf Med Soc Sahariennes. Phuza A.M.G, Paris, pp. 101–112. Levy, E., Hasin, Y., Navon, G., Horowitz, M., 1997. Chronic heat improves mechanical and metabolic response of trained rat heart on ischemia and reperfusion. Am. J. Phys. 272, H2085–H2094. Locke, M., 1997. The cellular stress response to exercise: role of stress proteins. Exerc. Sport Sci. Rev. 25, 105–136. Lorenzo, S., Minson, C.T., 2010. Heat acclimation improves cutaneous vascular function and sweating in trained cyclists. J. Appl. Physiol. (1985) 109, 1736–1743. Lorenzo, S., Halliwill, J.R., Sawka, M.N., Minson, C.T., 2010. Heat acclimation improves exercise performance. J. Appl. Physiol. (1985) 109, 1140–1147. Mack, G.W., Nadel, E.R., 1996. Body ﬂuid balance during heat stress in humans. In: MJ, Fregly, CM, Blatteis (Eds.), Environmental Physiolgy. Oxford University Press, New York, NY, pp. 187–214. McClung, J.P., Hasday, J.D., He, J.R., Montain, S.J., Cheuvront, S.N., Sawka, M.N., Singh, I.S., 2008. Exercise-heat acclimation in humans alters baseline levels and ex vivo heat inducibility of HSP72 and HSP90 in peripheral blood mononuclear cells. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R185–R191. Moran, D., Shapiro, Y., Meiri, U., Laor, A., Epstein, Y., Horowitz, M., 1996. Exercise in the heat: individual impacts of heat acclimation and exercise training on cardiovascular performance. J. Therm. Biol. 21, 171–181. Morimoto, T., 1990. Thermoregulation and body ﬂuids: role of blood volume and central venous pressure. Jpn. J. Physiol. 40, 165–179. Nadel, E.R., Mitchell, J.W., Saltin, B., Stolwijk, J.A., 1971. Peripheral modiﬁcations to the central drive for sweating. J. Appl. Physiol. 31, 828–833. Nadel, E.R., Pandolf, K.B., Roberts, M.F., Stolwijk, J.A., 1974. Mechanisms of thermal acclimation to exercise and heat. J. Appl. Physiol. 37, 515–520. Neal, R.A., Corbett, J., Massey,H.C., Tipton, M.J., 2015. Effect of short-term heat acclimation with permissive dehydration on thermoregulation and temperate exercise performance. Scand. J. Med. Sci. Sports. Nielsen, B., Hales, J.R., Strange, S., Christensen, N.J., Warberg, J., Saltin, B., 1993. Human circulatory and thermoregulatory adaptations with heat acclimation and exercise in a hot, dry environment. J. Physiol. 460, 467–485. Nielsen, B., Strange, S., Christensen, N.J., Warberg, J., Saltin, B., 1997. Acute and adaptive responses in humans to exercise in a warm, humid environment. Pﬂugers Arch. 434, 49–56. Nose, H., Mack, G.W., Shi, X.R., Nadel, E.R., 1988. Shift in body ﬂuid compartments after dehydration in humans. J. Appl. Physiol. (1985) 65, 318–324. Nybo, L., Rasmussen, P., Sawka, M.N.,2014. Performance in the heat—physiological factors of importance for hyperthermia-induced fatigue. Compr. Physiol. 4, 657–689. Ormerod, J.K., Elliott, T.A., Scheett, T.P., VanHeest, J.L., Armstrong, L.E., Maresh, C.M., 2003. Drinking behavior and perception of thirst in untrained women during 6 weeks of heat acclimation and outdoor training. Int. J. Sport Nutr. Exerc. Metab. 13, 15–28. Pandolf, K.B., 1998. Time course of heat acclimation and its decay. Int. J. Sports Med. 19, S157–S160. Pandolf, K.B., Burse, R.L., Goldman, R.F., 1977. Role of physical ﬁtness in heat acclimatisa- tion, decay and reinduction. Ergonomics 20, 399–408. Patterson, M.J., Stocks, J.M., Taylor, N.A., 2004a. Sustained and generalized extracellular ﬂuid expansion following heat acclimation. J. Physiol. 559, 327–334. Patterson, M.J., Stocks, J.M., Taylor, N.A.S., 2004b. Humid heat acclimation does not elicit a preferential sweat redistribution toward the limbs. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, R512–R518. Patterson, M.J., Stocks, J.M., Taylor, N.A., 2014. Whole-body ﬂuid distribution in humans during dehydration and recovery, before and after humid-heat acclimation induced using controlled hyperthermia. Acta Physiol. (Oxf.) 210, 899–912. Pearson, J., Low, D.A., Stohr, E., Kalsi, K., Ali, L., Barker, H., Gonzalez-Alonso, J., 2011. Hemodynamic responses to heat stress in the resting and exercising human leg: insight into the effect of temperature on skeletal muscle blood ﬂow. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300, R663–R673. Périard, J.D., Racinais, S., 2015. Self-paced exercise in hot and cool conditions is associated with the maintenance of %VO2peak within a narrow range. J. Appl. Physiol. 118, 1258–1265. Périard, J.D., Cramer, M.N., Chapman, P.G., Caillaud, C., Thompson, M.W., 2011. Cardiovascular strain impairs prolonged self-paced exercise in the heat. Exp. Physiol. 96, 134–144. Périard, J.D., Ruell, P., Caillaud, C., Thompson, M.W., 2012. Plasma Hsp72 (HSPA1A) and Hsp27 (HSPB1) expression under heat stress: inﬂuence of exercise intensity. Cell Stress Chaperones 17, 375–383. Périard, J.D., Racinais, S., Sawka, M.N., 2015a. Adaptations and mechanisms of human heat acclimation: applications for competitive athletes and sports. Scand. J. Med. Sci. Sports 25, 20–38. Périard, J.D., Ruell, P.A., Thompson, M.W., Caillaud, C., 2015b. Moderate- and high- intensity exhaustive exercise in the heat induce a similar increase in monocyte Hsp72. Cell Stress Chaperones 20, 1037–1042. Quinton, P.M., 2007. Cystic ﬁbrosis: lessons from the sweat gland. Physiology 22, 212–225. Racinais, S., Buchheit, M., Bilsborough, J., Bourdon, P.C., Cordy, J., Coutts, A.J., 2014. Physiological and performance responses to a training-camp in the heat in professional australian football players. Int. J. Sports Physiol. Perform. 9, 598–603. Racinais, S., Périard, J.D., Karlsen, A., Nybo, L., 2015. Effect of heat and heat-acclimatization on cycling time-trial performance and pacing. Med. Sci. Sports Exerc. 47, 601–606. Roberts, M.F., Wenger, C.B., Stolwijk, J.A., Nadel, E.R., 1977. Skin blood ﬂow and sweating changes following exercise training and heat acclimation. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 43, 133–137. Robinson, S., Turell, E.S., Belding, H.S., Horvath, S.M., 1943. Rapid acclimatization to work in hot climates. Am. J. Phys. 140, 168–176. Rolls, B.J., Rolls, E.T., 1982. Thirst. Cambridge University Press, New York. Rowell, L.B., 1974. Human cardiovascular adjustments to exercise and thermal stress. Physiol. Rev. 54, 75–159. Rowell, L.B., 1986. Circulatory adjustments to dynamic exercise and heat stress: competing controls. Human Circulation: Regulation during Physical Stress. Oxford University Press, New York, pp. 363–406. Rowell, L.B., Kranning, K.K., Kennedy, J.W., Evans, T.O., 1967.Central circulatory re- sponses to work in dry heat before and after acclimatization. J. Appl. Physiol. 22, 509–518. Rowell, L.B., Brengelmann, G.L., Blackmon, J.R., Twiss, R.D., Kusumi, F., 1968. Splanchnic blood ﬂow and metabolism in heat-stressed man. J. Appl. Physiol. 24, 475–484. Rowell, L.B., O'Leary, D.S., Kellogg Jr., D.L., 1996. Integration of cardiovascular control systems in dynamic exercise. In: LB, Rowell, JT, Shepherd (Eds.), Handbook of Physiology: Exercise Regulation and Integration of Multiple Systems. American Physiological Society, Bethesda, MD, pp. 770–838. Sato, K., Sato, F., 1983. Individual variations in structure and function of human eccrine sweat gland. Am. J. Phys. 245, R203–R208. Sato, F., Owen, M., Matthes, R., Sato, K., Gisolﬁ, C.V., 1990. Functional and morphological changes in the eccrine sweat gland with heat acclimation. J. Appl. Physiol. (1985) 69, 232–236. Sawka, M.N., Coyle, E.F., 1999. Inﬂuence of body water and blood volume on thermoreg- ulatory and exericse performance in the heat. Exerc. Sport Sci. Rev. 27, 167–218. Sawka, M.N., Young, A.J., 2000. Exercsie in hot and cold climates. In: WE, Garrett, DT, Kirkendall (Eds.), Exercise and Sport Science. Williams adn Wilkins, Philidelphia, PA, pp. 385–400. Sawka, M.N., Pandolf, K.B., Avellini, B.A., Shapiro, Y., 1983. Does heat acclimation lower the rate of metabolism elicited by muscular exercise? Aviat. Space Environ. Med. 54, 27–31. Sawka, M.N., Francesconi, R.P., Young, A.J., Pandolf, K.B., 1984. Inﬂuence of hydration level and body ﬂuids on exercise performance in the heat. JAMA 252, 1165–1169. Sawka, M.N., Young, A.J., Cadarette, B.S., Levine, L., Pandolf, K.B., 1985. Inﬂuence of heat stress and acclimation on maximal aerobic power. Eur. J. Appl. Physiol. Occup. Physiol. 53, 294–298. Sawka, M.N., Wenger, C.B., Pandolf, K.B., 1996. Thermoregulatory responses to acute exercise-heat stress and heat acclimation. In: MJ, Fregly, CM, Blatteis (Eds.), Handbook of Physiology, Section 4, Environmental Physiology. Oxford University Press, New York, Ny, pp. 157–185. Sawka, M.N., Leon, L.R., Montain, S.J., Sonna, L.A., 2011. Integrated physiological mechanisms of exercise performance, adaptation, and maladaptation to heat stress. Compr Physiol 1, 1883–1928. Sawka, M.N., Cheuvront, S.N., Keneﬁck, R.W., 2015. Hypohydration and human performance: impact of environmental and physiological mechanisms. Sports Med. 45, 51–60. Scoon, G.S., Hopkins, W.G., Mayhew, S., Cotter, J.D., 2007. Effect of post-exercise sauna bathing on the endurance performance of competitive male runners. J. Sci. Med. Sport 10, 259–262. Senay, L.C.J., 1970. Movement of water, protein and crystalloids between vascular and extra-vascular compartments in heat-exposed men during dehydration and follow- ing limited relief of dehydration. J. Physiol. 210, 617–635. Senay, L.C., 1972. Changes in plasma volume and protein content during exposures of working men to various tem- peratures before and after acclimatization to heat: separation of the roles of cutaneous and skeletal muscle circulation. J. Physiol. 224, 61–81. Senay, L.C.J., 1979. Effects of exercise in the heat on body ﬂuid distribution. Med. Sci. Sports 11, 42–48. Senay, L.C., 1986. An inquiry into the role of cardiac ﬁlling pressure in acclimatization to heat. Yale J. Bio. Med. 59, 247–256. Senay, L.C., Mitchell, D., Wyndham, C.H., 1976. Acclimatization in a hot, humid environ- ment: body ﬂuid adjustments. J. Appl. Physiol. 40, 786–796. 61J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52 –62 Shapiro, Y., Hubbard, R.W., Kimbrough, C.M., Pandolf, K.B., 1981. Physiological and hematologic responses to summer and winter dry-heat acclimation. J. Appl. Physiol. 50, 792–798. Shapiro, Y., Moran, D., Epstein, Y., 1998. Acclimatization strategies - Preparing for exercise in the heat. Int. J. Sports Med. 19, S161–S163. Shvartz, E., Shapiro, Y., Magazanik, A., Meroz, A., Birnfeld, H., Mechtinger, A., Shibolet, S., 1977. Heat acclimation, physical ﬁtness, and responses to exercise in temperate and hot environments. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 43, 678–683. Sundstroem, E.S., 1927. The physiological effects of tropical climates. Physiol. Rev. 7, 320–362. Takamata, A., Yoshida, T., Nishida, N., Morimoto, T., 2001. Relationship of osmotic inhibition in thermoregulatory responses and sweat sodium concentration in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R623–R629. Taylor, N.A.S., 2000. Principles and practices of heat adaptation. J. Hum. Environ. Syst. 4, 11–22. Taylor, N.A.S., 2014. Human heat adaptation. Comput. Phys. 4, 325–365. Wang, Z., Deurenberg, P., Wang, W., Pietrobelli, A., Baumgartner, R.N., Heymsﬁeld, S.B., 1999. Hydration of fat-free body mass: review and critique of a classic body- composition constant. Am. J. Clin. Nutr. 69, 833–841. Weller, A.S., Linnane, D.M., Jonkman, A.G., Daanen, H.A., 2007. Quantiﬁcation of the decay and re-induction of heat acclimation in dry-heat following 12 and 26 days without exposure to heat stress. Eur. J. Appl. Physiol. 102, 57–66. Wenger,C.B., 1988. Humanheat acclimatization.In: KB, Pandolf, MN, Sawka,RR,Gonzalez (Eds.), Human Performance Physiology and Environmental Medicine at Terrestrial Extremes. Benchmark Press, Indianapolis, IN, pp. 153–197. Werner, J., 1994. Beneﬁcial and detrimental effects of thermal adaptation. In: Zeisberger, E., Schönbaum, E., Lomax, P. (Eds.), Thermal Balance in Health and Disease, pp. 141–154 (Birkhäuser Basel). Williams, C.G., Wyndham, C.H., Morrison, J.F., 1967. Rate of loss of acclimatization in summer and winter. J. Appl. Physiol. 22, 21–26. Wingo, J.E., Ganio, M.S., Cureton, K.J., 2012. Cardiovascular drift during heat stress: implications for exercise prescription. Exerc. Sport Sci. Rev. 40, 88–94. Wyndham, C.H., 1951. Effect of acclimatization on circulatory responses to high environ- mental temperatures. J. Appl. Physiol. 4, 383–395. Wyndham, C.H., Benade, A.J., Williams, C.G., Strydom, N.B., Goldin, A., Heyns, A.J., 1968. Changes in central circulation and body ﬂuid spaces during acclimatization to heat. J. Appl. Physiol. 25, 586–593. Wyndham, C.H., Rogers, G.G., Senay, L.C., Mitchell, D., 1976. Acclimatization in a hot, humid environment: cardiovascular adjustments. J. Appl. Physiol. 40, 779–785. Yamazaki, F., Hamasaki, K., 2003. Heat acclimation increases skin vasodilation and sweating but not cardiac baroreﬂex responses in heat-stressed humans. J. Appl. Physiol. (1985) 95, 1567–1574. Yang, R.C., Mack, G.W., Wolf, R.R., Nadel, E.R.E., 1998. Albumin synthesis after intense intermittent exercise in human subjects. J. Appl. Physiol. Young, A.J., Sawka, M.N., Levin, L., Cadarette, B.S., Pandolf, K.B., 1985. Skeletal muscle metabolism during exercise is inﬂuenced by heat acclimation. J. Appl. Physiol. 59, 1929–1935. Zurawlew, M.J., Walsh, N.P., Fortes, M.B., Potter, C., 2015. Post-exercise hot water immersion induces heat acclimation and improves endurance exercise performance in the heat. Scand. J. Med. Sci. Sports. 62 J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52–62 cle circulation. J. Physiol. 224, 61–81. Senay, L.C.J., 1979. Effects of exercise in the heat on body ﬂuid distribution. Med. Sci. Sports 11, 42–48. Senay, L.C., 1986. An inquiry into the role of cardiac ﬁlling pressure in acclimatization to heat. Yale J. Bio. Med. 59, 247–256. Senay, L.C., Mitchell, D., Wyndham, C.H., 1976. Acclimatization in a hot, humid environ- ment: body ﬂuid adjustments. J. Appl. Physiol. 40, 786–796. 61J.D. Périard et al. / Autonomic Neuroscience: Basic and Clinical 196 (2016) 52 –62 Shapiro, Y., Hubbard, R.W., Kimbrough, C.M., Pandolf, K.B., 1981. Physiological and hematologic responses to summer and winter dry-heat acclimation. J. Appl. Physiol. 50, 792–798. Shapiro, Y., Moran, D., Epstein, Y., 1998. Acclimatization strategies - Preparing for exercise in the heat. Int. J. Sports Med. 19, S161–S163. Shvartz, E., Shapiro, Y., Magazanik, A., Meroz, A., Birnfeld, H., Mechtinger, A., Shibolet, S., 1977. Heat acclimation, physical ﬁtness, and responses to exercise in temperate and hot environments. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 43, 678–683. Sundstroem, E.S., 1927. The physiological effects of tropical climates. Physiol. Rev. 7, 320–362. Takamata, A., Yoshida, T., Nishida, N., Morimoto, T., 2001. Relationship of osmotic inhibition in thermoregulatory responses and sweat sodium concentration in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R623–R629. Taylor, N.A.S., 2000. Principles and practices of heat adaptation. J. Hum. Environ. Syst. 4, 11–22. Taylor, N.A.S., 2014. Human heat adaptation. Comput. Phys. 4, 325–365. Wang, Z., Deurenberg, P., Wang, W., Pietrobelli, A., Baumgartner, R.N., Heymsﬁeld, S.B., 1999. Hydration of fat-free body mass: review and critique of a classic body- composition constant. Am. J. Clin. Nutr. 69, 833–841. Weller, A.S., Linnane, D.M., Jonkman, A.G., Daanen, H.A., 2007. Quantiﬁcation of the decay and re-induction of heat acclimation in dry-heat following 12 and 26 days without exposure to heat stress. Eur. J. Appl. Physiol. 102, 57–66. Wenger,C.B., 1988. Humanheat acclimatization.In: KB, Pandolf, MN, Sawka,RR,Gonzalez (Eds.), Human Performance Physiology and Environmental Medicine at Terrestrial Extremes. Benchmark Press, Indianapolis, IN, pp. 153–197. Werner, J., 1994. Beneﬁcial and detrimental effects of thermal adaptation. In: Zeisberger, E., Schönbaum, E., Lomax, P. (Eds.), Thermal Balance in Health and Disease, pp. 141–154 (Birkhäuser Basel). Williams, C.G., Wyndham, C.H., Morrison, J.F., 1967. Rate of loss of acclimatization in summer and winter. J. Appl. Physiol. 22, 21–26. Wingo, J.E., Ganio, M.S., Cureton, K.J., 2012. Cardiovascular drift during heat stress: implications for exercise prescription. Exerc. Sport Sci. Rev. 40, 88–94. Wyndham, C.H., 1951. Effect of acclimatization on circulatory responses to high environ- mental temperatures. J. Appl. Physiol. 4, 383–395. Wyndham, C.H., Benade, A.J., Williams, C.G., Strydom, N.B., Goldin, A., Heyns, A.J., 1968. Changes in central circulation an