Advertisement

Mechanisms of orthostatic intolerance during heat stress

Published:December 16, 2015DOI:https://doi.org/10.1016/j.autneu.2015.12.005

      Highlights

      • Heat stress reduces orthostatic tolerance.
      • This impairment is due to heat stress induced changes in vascular resistance and cardiac output.
      • Effective countermeasures can improve orthostatic tolerance during heat stress.
      • Countermeasures can be improved by understanding inter-individual differences.

      Abstract

      Heat stress profoundly and unanimously reduces orthostatic tolerance. This review aims to provide an overview of the numerous and multifactorial mechanisms by which this occurs in humans. Potential causal factors include changes in arterial and venous vascular resistance and blood distribution, and the modulation of cardiac output, all of which contribute to the inability to maintain cerebral perfusion during heat and orthostatic stress. A number of countermeasures have been established to improve orthostatic tolerance during heat stress, which alleviate heat stress induced central hypovolemia (e.g., volume expansion) and/or increase peripheral vascular resistance (e.g., skin cooling). Unfortunately, these countermeasures can often be cumbersome to use with populations prone to syncopal episodes. Identifying the mechanisms of inter-individual differences in orthostatic intolerance during heat stress has proven elusive, but could provide greater insights into the development of novel and personalized countermeasures for maintaining or improving orthostatic tolerance during heat stress. This development will be especially impactful in occuational settings and clinical situations that present with orthostatic intolerance and/or central hypovolemia. Such investigations should be considered of vital importance given the impending increased incidence of heat events, and associated cardiovascular challenges that are predicted to occur with the ensuing changes in climate.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Albina G.
        • Cisneros L.F.
        • Laiño R.
        • Nobo U.L.
        • Ortega D.
        • Schwarz E.
        • Barja L.
        • Lagos R.
        • Giniger A.
        • Ameriso S.F.
        Transcranial Doppler monitoring during head upright tilt table testing in patients with suspected neurocardiogenic syncope.
        Europace. 2004; 6: 63-69
        • Allan J.
        • Crossley R.
        Effect of controlled elevation of body temperature on human tolerance to +G z acceleration.
        J. Appl. Physiol. 1972; 33: 418-420
        • Andersen E.B.
        • Boesen F.
        • Henriksen O.
        • Sonne M.
        Blood flow in skeletal muscle of tetraplegic man during postural changes.
        Clin. Sci. (Colch.). 1986; 70: 321-325
        • Anderson B.G.
        • Bell M.L.
        Weather-related mortality: how heat, cold, and heat waves affect mortality in the United States.
        Epidemiology. 2009; 20: 205
        • Armstrong L.
        • Hubbard R.
        • Jones B.
        • Daniels J.
        Preparing Alberto Salazar for the heat of the 1984 olympic marathon.
        Phys. Sportsmed. 1986; 14: 73-81
        • Bain A.R.
        • Smith K.J.
        • Lewis N.C.
        • Foster G.E.
        • Wildfong K.W.
        • Willie C.K.
        • Hartley G.L.
        • Cheung S.S.
        • Ainslie P.N.
        Regional changes in brain blood flow during severe passive hyperthermia; the effects of PaCO2 and extra-cranial blood flow.
        J. Appl. Physiol. 2013; 115: 653-659
        • Bain A.R.
        • Morrison S.A.
        • Ainslie P.N.
        Cerebral oxygenation and hyperthermia.
        Front. Physiol. 2014; 5
        • Bain A.R.
        • Nybo L.
        • Ainslie P.N.
        Cerebral vascular control and metabolism in heat stress.
        Compr. Physiol. 2015;
        • Bouchama A.
        • Knochel J.P.
        Heat stroke.
        N. Engl. J. Med. 2002; 346: 1978-1988
        • Brothers R.M.
        • Bhella P.S.
        • Shibata S.
        • Wingo J.E.
        • Levine B.D.
        • Crandall C.G.
        Cardiac systolic and diastolic function during whole body heat stress.
        Am. J. Physiol. Heart Circ. Physiol. 2009; 296: H1150-H1156
        • Brothers R.M.
        • Wingo J.E.
        • Hubing K.A.
        • Crandall C.G.
        The effects of reduced end-tidal carbon dioxide tension on cerebral blood flow during heat stress.
        J. Physiol. 2009; 587: 3921-3927
        • Brothers R.M.
        • Wingo J.E.
        • Hubing K.A.
        • Del Coso J.
        • Crandall C.G.
        Effect of whole body heat stress on peripheral vasoconstriction during leg dependency.
        J. Appl. Physiol. 2009; 107: 1704-1709
        • Brothers R.M.
        • Zhang R.
        • Wingo J.E.
        • Hubing K.A.
        • Crandall C.G.
        Effects of heat stress on dynamic cerebral autoregulation during large fluctuations in arterial blood pressure.
        J. Appl. Physiol. 2009; 107: 1722-1729
        • Brothers R.M.
        • Keller D.M.
        • Wingo J.E.
        • Ganio M.S.
        • Crandall C.G.
        Heat-stress-induced changes in central venous pressure do not explain interindividual differences in orthostatic tolerance during heat stress.
        J. Appl. Physiol. 2011; 110: 1283-1289
        • Brothers R.M.
        • Pecini R.
        • Dalsgaard M.
        • Bundgaard-Nielsen M.
        • Wilson T.E.
        • Secher N.H.
        • Crandall C.G.
        Beneficial effects of elevating cardiac preload on left-ventricular diastolic function and volume during heat stress: implications toward tolerance during a hemorrhagic insult.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014; 307: R1036-R1041
        • Bundgaard-Nielsen M.
        • Wilson T.E.
        • Seifert T.
        • Secher N.H.
        • Crandall C.G.
        Effect of volume loading on the Frank–Starling relation during reductions in central blood volume in heat-stressed humans.
        J. Physiol. 2010; 588: 3333-3339
        • Convertino V.A.
        Gender differences in autonomic functions associated with blood pressure regulation.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 1998; 275: R1909-R1920
        • Convertino V.A.
        Neurohumoral mechanisms associated with orthostasis: reaffirmation of the significant contribution of the heart rate response.
        Front. Physiol. 2014; : 5
        • Convertino V.A.
        • Sather T.M.
        Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in healthy subjects.
        Clin. Auton. Res. 2000; 10: 327-336
        • Convertino V.A.
        • Sather T.M.
        Vasoactive neuroendocrine responses associated with tolerance to lower body negative pressure in humans.
        Clin. Physiol. 2000; 20: 177-184
        • Convertino V.A.
        • Rickards C.A.
        • Ryan K.L.
        Autonomic mechanisms associated with heart rate and vasoconstrictor reserves.
        Clin. Auton. Res. 2012; 22: 123-130
        • Crandall C.G.
        Carotid baroreflex responsiveness in heat-stressed humans.
        Am. J. Physiol. Heart Circ. Physiol. 2000; 279: H1955-H1962
        • Crandall C.G.
        Heat stress and baroreflex regulation of blood pressure.
        Med. Sci. Sports Exerc. 2008; 40: 2063
        • Crandall C.G.
        • Gonzalez-Alonso J.
        Cardiovascular function in the heat-stressed human.
        Acta Physiol. 2010; 199: 407-423
        • Crandall C.G.
        • Wilson T.E.
        Human cardiovascular responses to passive heat stress.
        Compr. Physiol. 2014;
        • Crandall C.
        • Johnson J.
        • Kosiba W.
        • Kellogg D.
        Baroreceptor control of the cutaneous active vasodilator system.
        J. Appl. Physiol. 1996; 81: 2192-2198
        • Crandall C.G.
        • Shibasaki M.
        • Yen T.C.
        Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanisms.
        J. Physiol. 2002; 538: 599-605
        • Crandall C.G.
        • Cui J.
        • Wilson T.E.
        Effects of heat stress on baroreflex function in humans.
        Acta Physiol. Scand. 2003; 177: 321-328
        • Crandall C.G.
        • Wilson T.E.
        • Marving J.
        • Vogelsang T.W.
        • Kjaer A.
        • Hesse B.
        • Secher N.H.
        Effects of passive heating on central blood volume and ventricular dimensions in humans.
        J. Physiol. 2008; 586: 293-301
        • Crandall C.G.
        • Shibasaki M.
        • Wilson T.E.
        Insufficient cutaneous vasoconstriction leading up to and during syncopal symptoms in the heat stressed human.
        Am. J. Physiol. Heart Circ. Physiol. 2010; 299: H1168-H1173
        • Crandall C.G.
        • Wilson T.E.
        • Marving J.
        • Bundgaard-Nielsen M.
        • Seifert T.
        • Klausen T.
        • Andersen F.
        • Secher N.
        • Hesse B.
        Colloid volume loading does not mitigate decreases in central blood volume during simulated hemorrhage while heat stressed.
        J. Physiol. 2012; 590: 1287-1297
        • Cui J.
        • Wilson T.E.
        • Crandall C.G.
        Baroreflex modulation of sympathetic nerve activity to muscle in heat-stressed humans.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2002; 282: R252-R258
        • Cui J.
        • Wilson T.E.
        • Crandall C.G.
        Muscle sympathetic nerve activity during lower body negative pressure is accentuated in heat-stressed humans.
        J. Appl. Physiol. 2004; 96: 2103-2108
        • Cui J.
        • Wilson T.E.
        • Crandall C.G.
        Orthostatic challenge does not alter skin sympathetic nerve activity in heat-stressed humans.
        Auton. Neurosci. 2004; 116: 54-61
        • Cui J.
        • Durand S.
        • Levine B.D.
        • Crandall C.G.
        Effect of skin surface cooling on central venous pressure during orthostatic challenge.
        Am. J. Physiol. Heart Circ. Physiol. 2005; 289: H2429-H2433
        • Cui J.
        • Shibasaki M.
        • Low D.A.
        • Keller D.M.
        • Davis S.L.
        • Crandall C.G.
        Heat stress attenuates the increase in arterial blood pressure during the cold pressor test.
        J. Appl. Physiol. 2010; 109: 1354-1359
        • Cui J.
        • Shibasaki M.
        • Low D.A.
        • Keller D.M.
        • Davis S.L.
        • Crandall C.G.
        Muscle sympathetic responses during orthostasis in heat-stressed individuals.
        Clin. Auton. Res. 2011; 21: 381-387
        • Danet S.
        • Richard F.
        • Montaye M.
        • Beauchant S.
        • Lemaire B.
        • Graux C.
        • Cottel D.
        • Marécaux N.
        • Amouyel P.
        Unhealthy effects of atmospheric temperature and pressure on the occurrence of myocardial infarction and coronary deaths a 10-year survey: the lille-world health organization monica project.
        Circulation. 1999; 100: e1-e7
        • Davis S.L.
        • Crandall C.G.
        Heat stress alters hemodynamic responses during the Valsalva maneuver.
        J. Appl. Physiol. 2010; 108: 1591-1594
        • Durand S.
        • Cui J.
        • Williams K.
        • Crandall C.
        Skin surface cooling improves orthostatic tolerance in normothermic individuals.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004; 286: R199-R205
        • Durand S.
        • Davis S.
        • Cui J.
        • Crandall C.
        Exogenous nitric oxide inhibits sympathetically mediated vasoconstriction in human skin.
        J. Physiol. 2005; 562: 629-634
        • Easterling D.R.
        • Evans J.L.
        • Groisman P.Y.
        • Karl T.R.
        • Kunkel K.E.
        • Ambenje P.
        Observed variability and trends in extreme climate events: a brief review.
        Bull. Am. Meteorol. Soc. 2000; 81: 417-425
        • Easterling D.R.
        • Meehl G.A.
        • Parmesan C.
        • Chagnon S.A.
        • Karl T.R.
        • Mearns L.O.
        Climate extremes: observations, modeling and impacts.
        Science. 2000; 289: 2068-2074
        • Esler M.
        The 2009 Carl Ludwig Lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management.
        J. Appl. Physiol. 2010; 108: 227-237
        • Fan J.L.
        • Cotter J.D.
        • Lucas R.A.
        • Thomas K.
        • Wilson L.
        • Ainslie P.N.
        Human cardiorespiratory and cerebrovascular function during severe passive hyperthermia: effects of mild hypohydration.
        J. Appl. Physiol. 2008; 105: 433-445
        • Figueroa J.J.
        • Basford J.R.
        • Low P.A.
        Preventing and treating orthostatic hypotension: as easy as A, B, C.
        Cleve. Clin. J. Med. 2010; 77: 298
        • Folland C.K.
        • Karl T.R.
        • Salinger M.J.
        Observed climate variability and change.
        Weather. 2006; 57: 269-278
        • Fu Q.
        • Levine B.D.
        Pathophysiology of neurally mediated syncope: role of cardiac output and total peripheral resistance.
        Auton. Neurosci. 2014; 184: 24-26
        • Fu Q.
        • Arbab-Zadeh A.
        • Perhonen M.A.
        • Zhang R.
        • Zuckerman J.H.
        • Levine B.D.
        Hemodynamics of orthostatic intolerance: implications for gender differences.
        Am. J. Physiol. Heart Circ. Physiol. 2004; 286: H449-H457
        • Fu Q.
        • Shook R.P.
        • Okazaki K.
        • Hastings J.L.
        • Shibata S.
        • Conner C.L.
        • Palmer M.D.
        • Levine B.D.
        Vasomotor sympathetic neural control is maintained during sustained upright posture in humans.
        J. Physiol. 2006; 577: 679-687
        • Fujii N.
        • Honda Y.
        • Hayashi K.
        • Kondo N.
        • Koga S.
        • Nishiyasu T.
        Effects of chemoreflexes on hyperthermic hyperventilation and cerebral blood velocity in resting heated humans.
        Exp. Physiol. 2008; 93: 994-1001
        • Gagnon D.
        • Schlader Z.J.
        • Crandall C.G.
        Sympathetic activity during passive heat stress in healthy aged humans.
        J. Physiol. 2015; 593: 2225-2235
        • Ganio M.S.
        • Overgaard M.
        • Seifert T.
        • Secher N.H.
        • Johansson P.
        • Meyer M.
        • Crandall C.G.
        Effect of heat stress on cardiac output and systemic vascular conductance during simulated hemorrhage to pre-syncope in young men.
        Am. J. Physiol. Heart Circ. Physiol. 2012; 302: H1756-H1761
        • Gonzalez-Alonso J.
        • Crandall C.G.
        • Johnson J.A.
        The cardiovascular challenge of exercising in the heat.
        J. Physiol. 2008; 586: 45-53
        • Gorman A.J.
        • Proppe D.W.
        Mechanisms producing tachycardia in conscious baboons during environmental heat stress.
        J. Appl. Physiol. 1984; 56: 441-446
        • Greaney J.L.
        • Stanhewicz A.E.
        • Proctor D.N.
        • Alexander L.M.
        • Kenney W.L.
        Impairments in central cardiovascular function contribute to attenuated reflex vasodilation in aged skin.
        J. Appl. Physiol. 2015; (jap. 00729.02015)
        • Greenfield A.D.
        • Patterson G.C.
        On the capacity and distensibility of the blood vessels of the human forearm.
        J. Physiol. 1956; 131: 290-230+296
        • Greenleaf J.E.
        • Petersen T.W.
        • Gabrielsen A.
        • Pump B.
        • Bie P.
        • Christensen N.J.
        • Warberg J.
        • Videbaek R.
        • Simonson S.R.
        • Norsk P.
        Low LBNP tolerance in men is associated with attenuated activation of the renin-angiotensin system.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000; 279: R822-R829
        • Hagbarth K.E.
        • Hallin R.
        • Hongell A.
        • Torebjörk H.
        • Wallin B.
        General characteristics of sympathetic activity in human skin nerves.
        Acta Physiol. Scand. 1972; 84: 164-176
        • Hart E.C.
        • Joyner M.J.
        • Wallin B.G.
        • Charkoudian N.
        Sex, ageing and resting blood pressure: gaining insights from the integrated balance of neural and haemodynamic factors.
        J. Physiol. 2012; 590: 2069-2079
        • Heinonen I.
        • Brothers R.M.
        • Kemppainen J.
        • Knuuti J.
        • Kalliokoski K.K.
        • Crandall C.G.
        Local heating, but not indirect whole body heating, increases human skeletal muscle blood flow.
        J. Appl. Physiol. (1985). 2011; : 818-824
        • Henriksen O.
        Local sympathetic reflex mechanism in regulation of blood flow in human subcutaneous adipose tissue.
        Acta Physiol. Scand. Suppl. 1977; 450: 1-48
        • Henriksen O.
        • Sejrsen P.
        Local reflex in microcirculation in human skeletal muscle.
        Acta Physiol. Scand. 1977; 99: 19-26
        • Henriksen O.
        • Nielsen S.L.
        • Paaske W.P.
        • Sejrsen P.
        Autoregulation of blood flow in human cutaneous tissue.
        Acta Physiol. Scand. 1973; 89: 538-543
        • Henry J.
        • Gauer O.
        The influence of temperature upon venous pressure in the foot.
        J. Clin. Investig. 1950; 29: 855
        • Henry J.P.
        • Jacobs H.
        • Karstens A.
        • Gauer O.H.
        Influence of temperature on the pressure-volume.
        Am. J. Physiol. 1949; 159: 573-574
        • Hermosillo A.G.
        • Jordan J.L.
        • Vallejo M.
        • Kostine A.
        • Márquez M.F.
        • Cárdenas M.
        Cerebrovascular blood flow during the near syncopal phase of head-up tilt test: a comparative study in different types of neurally mediated syncope.
        Europace. 2006; 8: 199-203
        • Hinojosa-Laborde C.
        • Rickards C.A.
        • Ryan K.L.
        • Convertino V.A.
        Heart rate variability during simulated hemorrhage with lower body negative pressure in high and low tolerant subjects.
        Front. Physiol. 2011; 2: 85
        • Hodges G.J.
        • Kosiba W.A.
        • Zhao K.
        • Alvarez G.E.
        • Johnson J.M.
        The role of baseline in the cutaneous vasoconstrictor responses during combined local and whole body cooling in humans.
        Am. J. Physiol. Heart Circ. Physiol. 2007; 293: H3187-H3192
        • Horvath S.M.
        • Botelho S.Y.
        Orthostatic hypotension following hot or cold baths.
        J. Appl. Physiol. 1949; 1: 586-596
        • Huynen M.-M.
        • Martens P.
        • Schram D.
        • Weijenberg M.P.
        • Kunst A.E.
        The impact of heat waves and cold spells on mortality rates in the Dutch population.
        Environ. Health Perspect. 2001; 109: 463
        • Jose A.D.
        • Stitt F.
        • Collison D.
        The effects of exercise and changes in body temperature on the intrinsic heart rate in man.
        Am. Heart J. 1970; 79: 488-498
        • Kaiser R.
        • Le Tertre A.
        • Schwartz J.
        • Gotway C.A.
        • Daley W.R.
        • Rubin C.H.
        The effect of the 1995 heat wave in Chicago on all-cause and cause-specific mortality.
        Am. J. Public Health. 2007; 97: S158-S162
        • Keller D.
        • Cui J.
        • Davis S.
        • Low D.
        • Crandall C.
        Heat stress enhances arterial baroreflex control of muscle sympathetic nerve activity via increased sensitivity of burst gating, not burst area, in humans.
        J. Physiol. 2006; 573: 445-451
        • Keller D.M.
        • Low D.A.
        • Wingo J.E.
        • Brothers R.M.
        • Hastings J.
        • Davis S.L.
        • Crandall C.G.
        Acute volume expansion preserves orthostatic tolerance during whole-body heat stress in humans.
        J. Physiol. 2009; 587: 1131-1139
        • Keller D.M.
        • Sander M.
        • Stallknecht B.
        • Crandall C.G.
        α-Adrenergic vasoconstrictor responsiveness is preserved in the heated human leg.
        J. Physiol. 2010; 588: 3799-3808
        • Kellogg D.
        In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges.
        J. Appl. Physiol. 2006; 100: 1709-1718
        • Kenney W.L.
        • Craighead D.H.
        • Alexander L.M.
        Heat waves, aging and human cardiovascular health.
        Med. Sci. Sports Exerc. 2014; 46: 1891-1899
        • Kenney W.L.
        • Stanhewicz A.E.
        • Bruning R.S.
        • Alexander L.M.
        Blood pressure regulation III: what happens when one system must serve two masters: temperature and pressure regulation?.
        Eur. J. Appl. Physiol. 2014; 114: 467-479
        • Klabunde R.E.
        • LePorte A.D.
        • Wilson T.E.
        Effect of temperature on isoproterenol-induced increases in left ventricular developed pressure.
        J. Therm. Biol. 2013; 38: 369-373
        • Knowlton K.
        • Rotkin-Ellman M.
        • King G.
        • Margolis H.G.
        • Smith D.
        • Solomon G.
        • Trent R.
        • English P.
        The 2006 California heat wave: impacts on hospitalizations and emergency department visits.
        Environ. Health Perspect. 2009; 117: 61
        • Krogh A.
        The regulation of the supply of blood to the right Heart1.
        Skandinavisches Arch. Physiol. 1912; 27: 227-248
        • Lee J.F.
        • Harrison M.L.
        • Brown S.R.
        • Brothers R.M.
        The magnitude of heat stress-induced reductions in cerebral perfusion does not predict heat stress-induced reductions in tolerance to a simulated hemorrhage.
        J. Appl. Physiol. 2013; 114: 37-44
        • Lee J.F.
        • Christmas K.M.
        • Harrison M.L.
        • Hurr C.
        • Kim K.
        • Brothers R.M.
        Variability in orthostatic tolerance during heat stress: cerebrovascular reactivity to arterial carbon dioxide.
        Aviat. Space Environ. Med. 2014; 85: 624-630
        • Levine B.D.
        Regulation of central blood volume and cardiac filling in endurance athletes: the Frank–Starling mechanism as a determinant of orthostatic tolerance.
        Med. Sci. Sports Exerc. 1993; 25: 727-732
        • Levine B.D.
        • Giller C.A.
        • Lane L.D.
        • Buckey J.C.
        • Blomqvist C.G.
        Cerebral versus systemic hemodynamics during graded orthostatic stress in humans.
        Circulation. 1994; 90: 298-306
        • Lewis N.
        • Bain A.R.
        • MacLeod D.B.
        • Wildfong K.W.
        • Smith K.J.
        • Willie C.K.
        • Sanders M.L.
        • Numan T.
        • Morrison S.A.
        • Foster G.E.
        Impact of hypocapnia and cerebral perfusion on orthostatic tolerance.
        J. Physiol. 2014; 592: 5203-5219
        • Lind A.R.
        • Leithead C.S.
        • McNicol G.W.
        Cardiovascular changes during syncope induced by tilting men in the heat.
        J. Appl. Physiol. 1968; 25: 268-276
        • Low D.A.
        • Shibasaki M.
        • Davis S.L.
        • Keller D.M.
        • Crandall C.G.
        Does local heating-induced nitric oxide production attenuate vasoconstrictor responsiveness to lower body negative pressure in human skin?.
        J. Appl. Physiol. 2007; 102: 1839-1843
        • Low D.A.
        • Wingo J.E.
        • Keller D.M.
        • Davis S.L.
        • Zhang R.
        • Crandall C.G.
        Cerebrovascular responsiveness to steady-state changes in end-tidal CO2 during passive heat stress.
        J. Appl. Physiol. 2008; 104: 976-981
        • Low D.A.
        • Wingo J.E.
        • Keller D.M.
        • Davis S.L.
        • Cui J.
        • Zhang R.
        • Crandall C.G.
        Dynamic cerebral autoregulation during passive heat stress in humans.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009; 296: R1598-R1605
        • Low D.A.
        • Keller D.M.
        • Wingo J.E.
        • Brothers R.M.
        • Crandall C.G.
        Sympathetic nerve activity and whole body heat stress in humans.
        J. Appl. Physiol. 2011; 111: 1329-1334
        • Lu C.-C.
        • Diedrich A.
        • Tung C.-S.
        • Paranjape S.Y.
        • Harris P.A.
        • Byrne D.W.
        • Jordan J.
        • Robertson D.
        Water ingestion as prophylaxis against syncope.
        Circulation. 2003; 108: 2660-2665
        • Lucas R.A.
        • Cotter J.D.
        • Morrison S.
        • Ainslie P.N.
        The effects of ageing and passive heating on cardiorespiratory and cerebrovascular responses to orthostatic stress in humans.
        Exp. Physiol. 2008; 93: 1104-1117
        • Lucas R.A.
        • Ainslie P.N.
        • Fan J.L.
        • Wilson L.C.
        • Thomas K.N.
        • Cotter J.D.
        Skin cooling aids cerebrovascular function more effectively under severe than moderate heat stress.
        Eur. J. Appl. Physiol. 2010; 109: 101-108
        • Lucas R.A.
        • Ganio M.S.
        • Pearson J.
        • Crandall C.G.
        Sweat loss during heat stress contributes to subsequent reductions in lower-body negative pressure tolerance.
        Exp. Physiol. 2013; 98: 473-480
        • Lucas R.A.
        • Pearson J.
        • Schlader Z.J.
        • Crandall C.G.
        Hypercapnia-induced increases in cerebral blood flow do not improve lower body negative pressure tolerance during hyperthermia.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2013; 305: R604-R609
        • Lucas R.A.
        • Sarma S.
        • Schlader Z.J.
        • Pearson J.
        • Crandall C.G.
        Age-related changes to cardiac systolic and diastolic function during whole-body passive hyperthermia.
        Exp. Physiol. 2015; 100: 422-434
        • Mack G.W.
        • Nadel E.R.
        Body fluid balance during heat stress in humans.
        in: Comprehensive Physiology Supplement 14: Handbook of Physiology, Environmental Physiology. 2011: 187-214
        • Mano T.
        • Iwase S.
        Sympathetic nerve activity in hypotension and orthostatic intolerance.
        Acta Physiol. Scand. 2003; 177: 359-365
        • McHugh J.
        • Keller N.R.
        • Appalsamy M.
        • Thomas S.A.
        • Raj S.R.
        • Diedrich A.
        • Biaggioni I.
        • Jordan J.
        • Robertson D.
        Portal osmopressor mechanism linked to transient receptor potential vanilloid 4 and blood pressure control.
        Hypertension. 2010; 55: 1438-1443
        • Meehl G.A.
        • Tebaldi C.
        More intense, more frequent, and longer lasting heat waves in the 21st century.
        Science. 2004; 305: 994-997
        • Meehl G.A.
        • Stocker T.F.
        • Collins W.D.
        • Friedlingstein P.
        • Gaye A.T.
        • Gregory J.M.
        • Kitoh A.
        • Knutti R.
        • Murphy J.M.
        • Noda A.
        • Raper S.C.B.
        • Watterson I.G.
        • Weaver A.J.
        • Zhao Z.C.
        Global climate projections.
        in: Solomon S. Qin D. Manning M. Chen Z. Marquis M. Averyt K.B. Tignor M. Miller H.L. Climate Change 2007: The Physical Science Basis. Contribution of Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change. Cambridge University Press, Cambridge, U.K.2007
        • Meendering J.R.
        • Torgrimson B.N.
        • Houghton B.L.
        • Halliwill J.R.
        • Minson C.T.
        Menstrual cycle and sex affect hemodynamic responses to combined orthostatic and heat stress.
        Am. J. Physiol. Heart Circ. Physiol. 2005; 289: H631-H642
        • Minson C.T.
        • Wladkowski S.L.
        • Cardell A.F.
        • Pawelczyk J.A.
        • Kenney W.L.
        Age alters the cardiovascular response to direct passive heating.
        J. Appl. Physiol. 1998; 84: 1323-1332
        • Minson C.T.
        • Wladkowski S.L.
        • Pawelczyk J.A.
        • Kenney W.L.
        Age, splanchnic vasoconstriction, and heat stress during tilting.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 1999; 276: R203-R212
        • Monahan K.D.
        Effect of aging on baroreflex function in humans.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007; 293: R3-R12
        • Montgomery L.D.
        • Kirk P.J.
        • Payne P.A.
        • Gerber R.L.
        • Newton S.
        • Williams B.
        Cardiovascular responses of men and women to lower body negative pressure.
        Aviat. Space Environ. Med. 1977; 48: 138-145
        • Nelson M.D.
        • Haykowsky M.J.
        • Petersen S.R.
        • DeLorey D.S.
        • Cheng-Baron J.
        • Thompson R.B.
        Increased left ventricular twist, untwisting rates, and suction maintain global diastolic function during passive heat stress in humans.
        Am. J. Physiol. Heart Circ. Physiol. 2010; 298: H930-H937
        • Nelson M.D.
        • Altamirano-Diaz L.A.
        • Petersen S.R.
        • DeLorey D.S.
        • Stickland M.K.
        • Thompson R.B.
        • Haykowsky M.J.
        Left ventricular systolic and diastolic function during tilt-table positioning and passive heat stress in humans.
        Am. J. Physiol. Heart Circ. Physiol. 2011; 301: H599-H608
        • Nelson M.D.
        • Haykowsky M.J.
        • Stickland M.K.
        • Altamirano-Diaz L.A.
        • Willie C.K.
        • Smith K.J.
        • Petersen S.R.
        • Ainslie P.N.
        Reductions in cerebral blood flow during passive heat stress in humans: partitioning the mechanisms.
        J. Physiol. 2011; 589: 4053-4064
        • Niimi Y.
        • Matsukawa T.
        • Sugiyama Y.
        • Shamsuzzaman A.
        • Ito H.
        • Sobue G.
        • Mano T.
        Effect of heat stress on muscle sympathetic nerve activity in humans.
        J. Auton. Nerv. Syst. 1997; 63: 61-67
        • Normell L.A.
        • Wallin B.G.
        Sympathetic skin nerve activity and skin temperature changes in man.
        Acta Physiol. Scand. 1974; 91: 417-426
        • Nunneley S.A.
        • Stribley R.F.
        Heat and acute dehydration effects on acceleration response in man.
        J. Appl. Physiol. 1979; 47: 197-200
        • Ogoh S.
        • Sato K.
        • Okazaki K.
        • Miyamoto T.
        • Hirasawa A.
        • Morimoto K.
        • Shibasaki M.
        Blood flow distribution during heat stress: cerebral and systemic blood flow.
        J. Cereb. Blood Flow Metab. 2013; 33: 1915-1920
        • Ogoh S.
        • Sato K.
        • Okazaki K.
        • Miyamoto T.
        • Hirasawa A.
        • Shibasaki M.
        Hyperthermia modulates regional differences in cerebral blood flow to changes in CO2.
        J. Appl. Physiol. 2014; 117: 46-52
        • Organization W.M.
        Warming Trend Continues in 2014, Hottest Year on Record.
        Genva, Switzerland2015
        • Paulson O.
        • Strandgaard S.
        • Edvinsson L.
        Cerebral autoregulation.
        Cerebrovasc. Brain Metab. Rev. 1989; 2: 161-192
        • Pearson J.
        • Low D.A.
        • Stohr E.
        • Kalsi K.
        • Ali L.
        • Barker H.
        • Gonzalez-Alonso J.
        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. 2011; 300: R663-R673
        • Pearson J.
        • Ganio M.S.
        • Lucas R.A.
        • Babb T.G.
        • Crandall C.G.
        Heat stress does not augment ventilatory responses to presyncopal limited lower body negative pressure.
        Exp. Physiol. 2013; 98: 1156-1163
        • Pearson J.
        • Lucas R.A.
        • Schlader Z.J.
        • Zhao J.
        • Gagnon D.
        • Crandall C.G.
        Active and passive heat stress similarly compromise tolerance to a simulated hemorrhagic challenge.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014; 307: R822-R827
        • Ratcliffe R.A.S.
        • Weller J.
        • Collison P.
        Variability in the frequency of unusual weather over approximately the last century.
        Q. J. R. Meteorol. Soc. 2006; 104: 243-255
        • Rickards C.A.
        • Ryan K.L.
        • Cooke W.H.
        • Convertino V.A.
        Tolerance to central hypovolemia: the influence of oscillations in arterial pressure and cerebral blood velocity.
        J. Appl. Physiol. 2011; 111: 1048-1058
        • Ross E.Z.
        • Cotter J.D.
        • Wilson L.
        • Fan J.L.
        • Lucas S.J.
        • Ainslie P.N.
        Cerebrovascular and corticomotor function during progressive passive hyperthermia in humans.
        J. Appl. Physiol. 2012; 112: 748-758
        • Rowell L.B.
        Human cardiovascular adjustments to exercise and thermal-stress.
        Physiol. Rev. 1974; 54: 75-159
        • Rowell L.
        Cardiovascular aspects of human thermoregulation.
        Circ. Res. 1983; 52: 367-379
        • Rowell L.B.
        Cutaneous and Skeletal Muscle Circulations, Human Circulation Regulation During Physical Stress.
        Oxford University Press, New York1986: 96-116
        • Rowell L.B.
        Thermal Stress, Human Circulation Regulation During Physical Stress.
        Oxford Univeristy Press, New York1986: 174-212
        • Rowell L.
        Hyperthermia: a hyperadrenergic state.
        Hypertension. 1990; 15: 505-507
        • Rowell L.B.
        • Brengelmann G.L.
        • Blackmon J.R.
        • Twiss R.D.
        • Kusumi F.
        Splanchnic blood flow and metabolism in heat-stressed man.
        J. Appl. Physiol. 1968; 24: 475-484
        • Rowell L.B.
        • Brengelmann G.L.
        • Murray J.A.
        Cardiovascular responses to sustained high skin temperature in resting man.
        J. Appl. Physiol. 1969; 27: 673-680
        • Rowell L.B.
        • Brengelmann G.L.
        • Detry J.
        • Wyss C.
        Venomotor responses to local and remote thermal stimuli to skin in exercising man.
        J. Appl. Physiol. 1971; 30: 72-77
        • Rowell L.B.
        • Detry J.R.
        • Profant G.R.
        • Wyss C.
        Splanchnic vasoconstriction in hyperthermic man — role of falling blood pressure.
        J. Appl. Physiol. 1971; 31: 864-869
        • Rutan G.H.
        • Hermanson B.
        • Bild D.E.
        • Kittner S.J.
        • LaBaw F.
        • Tell G.S.
        Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group.
        Hypertension. 1992; 19: 508-519
        • Sather T.M.
        • Goldwater D.J.
        • Montgomery L.D.
        • Convertino V.A.
        Cardiovascular dynamics associated with tolerance to lower body negative pressure.
        Aviat. Space Environ. Med. 1986; 57: 413-419
        • Sato K.
        • Fisher J.P.
        • Seifert T.
        • Overgaard M.
        • Secher N.H.
        • Ogoh S.
        Blood flow in internal carotid and vertebral arteries during orthostatic stress.
        Exp. Physiol. 2012; 97: 1272-1280
        • Schlader Z.J.
        • Crandall C.G.
        Normothermic central hypovolemia tolerance reflects hyperthermic tolerance.
        Clin. Auton. Res. 2014; 24: 119-126
        • Schlader Z.J.
        • Lucas R.A.
        • Pearson J.
        • Crandall C.G.
        Hyperthermia does not alter the increase in cerebral perfusion during cognitive activation.
        Exp. Physiol. 2013; 98: 1597-1607
        • Schlader Z.J.
        • Seifert T.
        • Wilson T.E.
        • Bundgaard-Nielsen M.
        • Secher N.H.
        • Crandall C.G.
        Acute volume expansion attenuates hyperthermia-induced reductions in cerebral perfusion during simulated hemorrhage.
        J. Appl. Physiol. 2013; 114: 1730-1735
        • Schlader Z.J.
        • Rivas E.
        • Soller B.R.
        • Convertino V.A.
        • Crandall C.G.
        Tissue oxygen saturation during hyperthermic progressive central hypovolemia.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014; 307: R731-R736
        • Schlader Z.J.
        • Gagnon D.
        • Rivas E.
        • Convertino V.A.
        • Crandall C.G.
        Fluid restriction during exercise in the heat reduces tolerance to progressive central hypovolemia.
        Exp. Physiol. 2015;
        • Schwartz C.E.
        • Stewart J.M.
        The arterial baroreflex resets with orthostasis.
        Front. Physiol. 2012; 3
        • Shibasaki M.
        • Davis S.L.
        • Cui J.
        • Low D.A.
        • Keller D.M.
        • Durand S.
        • Crandall C.G.
        Neurally mediated vasoconstriction is capable of decreasing skin blood flow during orthostasis in the heat-stressed human.
        J. Physiol. 2006; 575: 953-959
        • Shibasaki M.
        • Durand S.
        • Davis S.L.
        • Cui J.
        • Low D.A.
        • Keller D.M.
        • Crandall C.G.
        Endogenous nitric oxide attenuates neutrally mediated cutaneous vasoconstriction.
        J. Physiol. 2007; 585: 627-634
        • Shibasaki M.
        • Low D.A.
        • Davis S.L.
        • Crandall C.G.
        Nitric oxide inhibits cutaneous vasoconstriction to exogenous norepinephrine.
        J. Appl. Physiol. 2008; 105: 1504-1508
        • Shibasaki M.
        • Umemoto Y.
        • Kinoshita T.
        • Kouda K.
        • Ito T.
        • Nakamura T.
        • Crandall C.G.
        • Tajima F.
        The role of cardiac sympathetic innervation and skin thermoreceptors on cardiac responses during heat stress.
        Am. J. Physiol. Heart Circ. Physiol. 2015; (ajpheart. 00911.02014)
        • Shiraki K.
        • Sagawa S.
        • Yousef M.
        • Konda N.
        • Miki K.
        Physiological responses of aged men to head-up tilt during heat exposure.
        J. Appl. Physiol. 1987; 63: 576-581
        • Shvartz E.
        • Meyerstein N.
        Effect of heat and natural acclimatization to heat on tilt tolerance of men and women.
        J. Appl. Physiol. 1970; 28: 428-432
        • Skagen K.
        • Bonde-Petersen F.
        Regulation of subcutaneous blood flow during head-up tilt (45°) in normals.
        Acta Physiol. Scand. 1982; 114: 31-35
        • Skagen K.
        • Jensen K.
        • Henriksen O.
        • Knudsen L.
        Sympathetic reflex control of subcutaneous blood flow in tetraplegic man during postural changes.
        Clin. Sci. (Colch.). 1982; 62: 605-609
        • Snyder K.A.
        • Shamimi-Noori S.
        • Wilson T.E.
        • Monahan K.D.
        Age-and limb-related differences in the vasoconstrictor response to limb dependency are not mediated by a sympathetic mechanism in humans.
        Acta Physiol. 2012; 205: 372-380
        • Stöhr E.J.
        • González-Alonso J.
        • Pearson J.
        • Low D.A.
        • Ali L.
        • Barker H.
        • Shave R.
        Effects of graded heat stress on global left ventricular function and twist mechanics at rest and during exercise in healthy humans.
        Exp. Physiol. 2011; 96: 114-124
        • Van Lieshout J.J.
        • Wieling W.
        • Karemaker J.M.
        • Secher N.H.
        Syncope, cerebral perfusion, and oxygenation.
        J. Appl. Physiol. 2003; 94: 833-848
        • Vandecasteele G.
        • Eschenhagen T.
        • Scholz H.
        • Stein B.
        • Verde I.
        • Fischmeister R.
        Muscarinic and β-adrenergic regulation of heart rate, force of contraction and calcium current is preserved in mice lacking endothelial nitric oxide synthase.
        Nat. Med. 1999; 5: 331-334
        • Vandentorren S.
        • Bretin P.
        • Zeghnoun A.
        • Mandereau-Bruno L.
        • Croisier A.
        • Cochet C.
        • Ribéron J.
        • Siberan I.
        • Declercq B.
        • Ledrans M.
        August 2003 heat wave in France: risk factors for death of elderly people living at home.
        Eur. J. Pub. Health. 2006; 16: 583-591
        • Vanhoutte P.M.
        • Shepherd J.T.
        Effect of temperature on reactivity of isolated cutaneous veins of the dog.
        Am. J. Physiol. 1970; 218: 187-190
        • Vissing S.
        • Secher N.
        • Victor R.
        Mechanisms of cutaneous vasoconstriction during upright posture.
        Acta Physiol. Scand. 1997; 159: 131-138
        • Wallin B.G.
        • Sundlöf G.
        • Delius W.
        The effect of carotid sinus nerve stimulation on muscle and skin nerve sympathetic activity in man.
        Pflugers Arch. 1975; 358: 101-110
        • Waters W.W.
        • Ziegler M.G.
        • Meck J.V.
        Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance.
        J. Appl. Physiol. 2002; 92: 586-594
        • Webb-Peploe M.M.
        Effect of changes in central body temperature on capacity elements of limb and spleen.
        Am. J. Physiol. 1969; 216: 643-646
        • Webb-Peploe M.M.
        • Shepherd J.T.
        Peripheral mechanism involved in response of dog's cutaneous veins to local temperature change.
        Circ. Res. 1968; 23: 701-708
        • Webb-Peploe M.M.
        • Shepherd J.T.
        Response of dogs' cutaneous veins to local and central temperature changes.
        Circ. Res. 1968; 23: 693-699
        • Wieling W.
        • France C.R.
        • van Dijk N.
        • Kamel H.
        • Thijs R.D.
        • Tomasulo P.
        Physiologic strategies to prevent fainting responses during or after whole blood donation.
        Transfusion. 2011; 51: 2727-2738
        • Wilson T.E.
        • Cui J.
        • Crandall C.G.
        Absence of arterial baroreflex modulation of skin sympathetic activity and sweat rate during whole-body heating in humans.
        J. Physiol. 2001; 536: 615-623
        • Wilson T.E.
        • Cui J.
        • Crandall C.G.
        Effect of whole-body and local heating on cutaneous vasoconstrictor responses in humans.
        Auton. Neurosci. 2002; 97: 122-128
        • Wilson T.E.
        • Cui J.
        • Zhang R.
        • Witkowski S.
        • Crandall C.G.
        Skin cooling maintains cerebral blood flow velocity and orthostatic tolerance during tilting in heated humans.
        J. Appl. Physiol. 2002; 93: 85-91
        • Wilson T.E.
        • Cui J.
        • Crandall C.G.
        Mean body temperature does not modulate eccrine sweat rate during upright tilt.
        J. Appl. Physiol. 2005; 98: 1207-1212
        • Wilson T.E.
        • Cui J.
        • Zhang R.
        • Crandall C.G.
        Heat stress reduces cerebral blood velocity and markedly impairs orthostatic tolerance in humans.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006; 291: R1443-R1448
        • Wilson T.E.
        • Sauder C.L.
        • Kearney M.L.
        • Kuipers N.T.
        • Leuenberger U.A.
        • Monahan K.D.
        • Ray C.A.
        Skin-surface cooling elicits peripheral and visceral vasoconstriction in humans.
        J. Appl. Physiol. 2007; 103: 1257-1262
        • Wilson T.E.
        • Tollund C.
        • Yoshiga C.C.
        • Dawson E.A.
        • Nissen P.
        • Secher N.H.
        • Crandall C.G.
        Effects of heat and cold stress on central vascular pressure relationships during orthostasis in humans.
        J. Physiol. 2007; 585: 279-285
        • Wilson T.E.
        • Brothers R.M.
        • Tollund C.
        • Dawson E.A.
        • Nissen P.
        • Yoshiga C.C.
        • Jons C.
        • Secher N.H.
        • Crandall C.G.
        Effect of thermal stress on frank-starling relations in humans.
        J. Physiol. 2009; 587: 3383-3392
        • Yamazaki F.
        • Monji K.
        • Sogabe Y.
        • Sone R.
        Cardiac and peripheral vascular responses to head-up tilt during whole body thermal stress.
        J. UOEH. 2000; 22: 147-158
        • Yamazaki F.
        • Okuno C.
        • Nagamatsu S.
        • Sone R.
        Effects of whole-body and local thermal stress on hydrostatic volume changes in the human calf.
        Eur. J. Appl. Physiol. 2002; 88: 61-66
        • Yamazaki F.
        • Yamauchi K.
        • Tsutsui Y.
        • Endo Y.
        • Sagawa S.
        • Shiraki K.
        Whole body heating reduces the baroreflex response of sympathetic nerve activity during Valsalva straining.
        Auton. Neurosci. 2003; 103: 93-99
        • Yamazaki F.
        • Nakayama Y.
        • Sone R.
        Whole-body heating decreases skin vascular response to low orthostatic stress in the lower extremities.
        J. Physiol. Sci. 2006; 56: 157-164
        • Zitnik R.S.
        • Ambrosioni E.
        • Shepherd J.T.
        Effect of temperature on cutaneous venomotor reflexes in man.
        J. Appl. Physiol. 1971; 31: 507-512

      CHORUS Manuscript

      View Open Manuscript