Evidence for temperature-mediated regional increases in cerebral blood flow during exercise

Hannah G Caldwell, Geoff B Coombs, Connor A Howe, Ryan L Hoiland, Alexander Patrician, Samuel J E Lucas, Philip N Ainslie, Hannah G Caldwell, Geoff B Coombs, Connor A Howe, Ryan L Hoiland, Alexander Patrician, Samuel J E Lucas, Philip N Ainslie

Abstract

Aerobic exercise elicits increases in cerebral blood flow (CBF), as well as core body temperature; however, the isolated influence of temperature on CBF regulation during exercise has not been investigated The present study assessed CBF regulation and neurovascular coupling during submaximal cycling exercise and temperature-matched passive heat stress during isocapnia (i.e. end-tidal PCO2 was held constant) Submaximal cycling exercise and temperature-matched passive heat stress provoked ∼16% increases in vertebral artery blood flow, independent of changes in end-tidal PCO2 and blood pressure External carotid artery blood flow increased by ∼43% during both exercise and passive heat stress, with no change in internal carotid artery blood flow Neurovascular coupling (i.e. the relationship between local increases in cerebral metabolism and appropriately matched increases in regional cerebral blood flow) is preserved during both exercise and temperature-matched passive heat stress ABSTRACT: Acute moderate-intensity exercise increases core temperature (Tc ; +0.7-0.8°C); however, such exercise increases cerebral blood flow (CBF; +10-20%) mediated via small elevations in arterial PCO2 and metabolism. The present study aimed to isolate the role of Tc from PCO2 on CBF regulation during submaximal exercise. Healthy adults (n = 11; 10 males/one female; 26 ± 4 years) participated in two interventions each separated by ≥48 h: (i) 60 min of semi-recumbent cycling (EX; 50% workload max) and (ii) 75 min of passive heat stress (HS; 49°C water-perfused suit) to match the exercise-induced increases in Tc (EX: Δ0.75 ± 0.33°C vs. HS: Δ0.77 ± 0.33°C, P = 0.855). Blood flow (Q) in the internal and external carotid arteries (ICA and ECA, respectively) and vertebral artery (VA) (Duplex ultrasound) was measured. End-tidal PCO2 and PO2 were effectively clamped to resting values within each condition. The QICA was unchanged with EX and HS interventions (P = 0.665), consistent with the unchanged end-tidal PCO2 (P = 0.327); whereas, QVA was higher throughout both EX and HS (EX: Δ16 ± 21% vs. HS: Δ16 ± 23%, time effect: P = 0.006) with no between condition differences (P = 0.785). These increases in QVA contributed to higher global CBF throughout both EX and HS (EX: Δ12 ± 20% vs. HS: Δ14 ± 14%, time effect: P = 0.029; condition effect: P = 0.869). The QECA increased throughout both EX and HS (EX: Δ42 ± 58% vs. HS: Δ53 ± 28%, time effect: P < 0.001; condition effect: P = 0.628). Including blood pressure as a covariate did not alter these CBF findings (all P > 0.05). Overall, these data provide new evidence for temperature-mediated elevations in posterior CBF during exercise that are independent of changes in PCO2 and blood pressure.

Keywords: cerebrovascular; exercise; temperature.

© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.

References

    1. Ainslie PN & Hoiland RL (2014). Transcranial Doppler ultrasound: valid, invalid, or both? J Appl Physiol 117, 1081-1083.
    1. Bain AR, Hoiland RL, Donnelly J, Nowak-Flück D, Sekhon M, Tymko MM, Greiner JJ, DeSouza CA, Ainslie PN (2020). Cerebral metabolism, oxidation, and inflammation in severe passive hyperthermia with and without respiratory alkalosis. J Physiol 598, 943-954.
    1. Bain AR, Nybo L & Ainslie PN (2015). Cerebral vascular control and metabolism in heat stress. Compr Physiol 5, 1345-1380.
    1. Bain AR, Smith KJ, Lewis NC, Foster GE, Wildfong KW, Willie CK, Hartley GL, Cheung SS & Ainslie PN (2013). Regional changes in brain blood flow during severe passive hyperthermia: effects of PaCO2 and extracranial blood flow. J Appl Physiol 115, 653-659.
    1. Bouchama A & Knochel JP (2002). Heat stroke. N Engl J Med 346, 1978-1988.
    1. Boulant JA (2000). Role of the preoptic-anterior hypothalamus in thermoregulation and fever. Clin Infect Dis 31(Suppl 5), S157-S161.
    1. Brothers RM, Ganio MS, Hubing KA, Hastings JL & Crandall CG (2011). End-tidal carbon dioxide tension reflects arterial carbon dioxide tension in the heat-stressed human with and without simulated hemorrhage. Am J Physiol Regul Integr Comp Physiol 300, R978-R983.
    1. Brothers RM, Wingo JE, Hubing KA & Crandall CG (2009). The effects of reduced end-tidal carbon dioxide tension on cerebral blood flow during heat stress. J Physiol (Lond) 587, 3921-3927.
    1. Brunt VE, Howard MJ, Francisco MA, Ely BR & Minson CT (2016). Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans. J Physiol (Lond) 594, 5329-5342.
    1. Brunt VE, Wiedenfeld-Needham K, Comrada LN & Minson CT (2018). Passive heat therapy protects against endothelial cell hypoxia-reoxygenation via effects of elevations in temperature and circulating factors. J Physiol (Lond) 596, 4831-4845.
    1. Carter HH, Dawson EA, Birk GK, Spence AL, Naylor LH, Cable NT, Thijssen DHJ & Green DJ (2013). Effect of SR manipulation on conduit artery dilation in humans. Hypertension 61, 143-150.
    1. Carter HH, Spence AL, Atkinson CL, Pugh CJA, Naylor LH & Green DJ (2014). Repeated core temperature elevation induces conduit artery adaptation in humans. Eur J Appl Physiol 114, 859-865.
    1. Coombs GB, Vucina D, Caldwell HG, Barak OF, Mijacika T, Lee AHX, Sarafis ZK, Squair JW, Krassioukov AV, Phillips AA, Dujic Z & Ainslie PN (2019). Cerebrovascular function is preserved during mild hyperthermia in cervical spinal cord injury. Spinal Cord 81, 723-726.
    1. Cranston WI & Rosendorff C (1971). Local blood flow, cerebrovascular autoregulation and CO2 responsiveness in the rabbit hypothalamus. J Physiol (Lond) 215, 577-590.
    1. Donnelly C, Frobese AS, MACKRELL TN, STONE HH & TRUTER MR (1956). The effect of lowered body temperature on the cerebral hemodynamics and metabolism of man. Surg Forum 6, 129-134.
    1. Fan J-L, Cotter JD, Lucas RAI, Thomas K, Wilson L & Ainslie PN (2008). Human cardiorespiratory and cerebrovascular function during severe passive hyperthermia: effects of mild hypohydration. J Appl Physiol 105, 433-445.
    1. Fisher JP, Hartwich D, Seifert T, Olesen ND, McNulty CL, Nielsen HB, van Lieshout JJ & Secher NH (2013). Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals. J Physiol (Lond) 591, 1859-1870.
    1. Fujii N, Tsuji B, Honda Y, Kondo N & Nishiyasu T (2015). Effect of short-term exercise-heat acclimation on ventilatory and cerebral blood flow responses to passive heating at rest in humans. J Appl Physiol 119, 435-444.
    1. Hiura M, Nariai T, Sakata M, Muta A, Ishibashi K, Wagatsuma K, Tago T, Toyohara J, Ishii K & Maehara T (2018). Response of cerebral blood flow and blood pressure to dynamic exercise: a study using PET. Int J Sports Med 39, 181-188.
    1. Hodder SG & Parsons K (2007). The effects of solar radiation on thermal comfort. Int J Biometeorol 51, 233-250.
    1. Hoiland RL & Ainslie PN (2016). CrossTalk proposal: The middle cerebral artery diameter does change during alterations in arterial blood gases and blood pressure. J Physiol (Lond) 594, 4073-4075.
    1. Iadecola C (2017). The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 96, 17-42.
    1. Ide K & Secher NH (2000). Cerebral blood flow and metabolism during exercise. Prog Neurobiol 61, 397-414.
    1. Jarmuszkiewicz W, Woyda-Ploszczyca A, Koziel A, Majerczak J & Zoladz JA (2015). Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria. Free Radic Biol Med 83, 12-20.
    1. Jones NL, Robertson DG & Kane JW (1979). Difference between end-tidal and arterial PCO2 in exercise. J Appl Physiol Respir Environ Exerc Physiol 47, 954-960.
    1. Kunutsor SK, Khan H, Zaccardi F, Laukkanen T, Willeit P & Laukkanen JA (2018). Sauna bathing reduces the risk of stroke in Finnish men and women: a prospective cohort study. Neurology 90, e1937-e1944.
    1. Larsen TS, Rasmussen P, Overgaard M, Secher NH & Nielsen HB (2008). Non-selective β-adrenergic blockade prevents reduction of the cerebral metabolic ratio during exhaustive exercise in humans. J Physiol (Lond) 586, 2807-2815.
    1. Laukkanen T, Kunutsor SK, Zaccardi F, Lee E, Willeit P, Khan H & Laukkanen JA (2018). Acute effects of sauna bathing on cardiovascular function. J Hum Hypertens 32, 129-138.
    1. Lin A-L, Fox PT, Yang Y, Lu H, Tan L-H & Gao J-H (2008). Evaluation of MRI models in the measurement of CMRO2 and its relationship with CBF. Magn Reson Med 60, 380-389.
    1. Liu Z, Vargas F, Stansbury D, Sasse SA & Light RW (1995). Comparison of the end-tidal arterial PCO2 gradient during exercise in normal subjects and in patients with severe COPD. Chest 107, 1218-1224.
    1. MacVeigh I, Cook DJ, Orszulak TA, Daly RC & Munnikhuysen DE (1997). Nitrous oxide method of measuring cerebral blood flow during hypothermic cardiopulmonary bypass. Ann Thorac Surg 63, 736-740.
    1. Mashour GA & Boock RJ (1999). Effects of shear stress on nitric oxide levels of human cerebral endothelial cells cultured in an artificial capillary system. Brain Res 842, 233-238.
    1. McAllen RM & McKinley MJ (2018). Efferent thermoregulatory pathways regulating cutaneous blood flow and sweating. Handb Clin Neurol 156, 305-316.
    1. Mekjavić IB & Rempel ME (1990). Determination of esophageal probe insertion length based on standing and sitting height. J Appl Physiol 69, 376-379.
    1. Metzger A, Le Bars E, Deverdun J, Molino F, Maréchal B, Picot M-C, Ayrignac X, Carra C, Bauchet L, Krainik A, Labauge P & Menjot de Champfleur N (2018). Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients? Eur Radiol 28, 1204-1214.
    1. Nelson MD, Haykowsky MJ, Stickland MK, Altamirano-Diaz LA, Willie CK, Smith KJ, Petersen SR & Ainslie PN (2011). Reductions in cerebral blood flow during passive heat stress in humans: partitioning the mechanisms. J Physiol (Lond) 589, 4053-4064.
    1. Nunneley SA, Martin CC, Slauson JW, Hearon CM, Nickerson LDH & Mason PA (2002). Changes in regional cerebral metabolism during systemic hyperthermia in humans. J Appl Physiol 92, 846-851.
    1. Nybo L, Møller K, Volianitis S, Nielsen B & Secher NH (2002). Effects of hyperthermia on cerebral blood flow and metabolism during prolonged exercise in humans. J Appl Physiol 93, 58-64.
    1. Ogoh S & Ainslie PN (2009). Regulatory mechanisms of cerebral blood flow during exercise: new concepts. Exerc Sport Sci Rev 37, 123-129.
    1. Ogoh S, Sato K, Okazaki K, Miyamoto T, Hirasawa A & Shibasaki M (2014). Hyperthermia modulates regional differences in cerebral blood flow to changes in CO2. J Appl Physiol 117, 46-52.
    1. Ogoh S, Sato K, Okazaki K, Miyamoto T, Hirasawa A, Morimoto K & Shibasaki M (2013). Blood flow distribution during heat stress: cerebral and systemic blood flow. J Cereb Blood Flow Metab 33, 1915-1920.
    1. Olszewski J (1952). The Thalamus of the Macaca Mulatta. New York: Karger.
    1. Ota A, Takeda R, Imai D, Naghavi N, Kawai E, Saho K, Morita E, Suzuki Y, Yokoyama H, Miyagawa T & Okazaki K (2019). The effects of aging on the distribution of cerebral blood flow with postural changes and mild hyperthermia. Eur J Appl Physiol 119, 1261-1272.
    1. Phillips AA, Chan FH, Zheng MMZ, Krassioukov AV & Ainslie PN (2016). Neurovascular coupling in humans: physiology, methodological advances and clinical implications. J Cereb Blood Flow Metab 36, 647-664.
    1. Phillips AA, Squair JR, Currie KD, Tzeng YC, Ainslie PN & Krassioukov AV (2017). 2015 ParaPan American Games: autonomic function, but not physical activity, is associated with vascular-cognitive impairment in spinal cord injury. J Neurotrauma 34, 1283-1288.
    1. Qian S, Jiang Q, Liu K, Li B, Li M, Li L, Yang X, Yang Z & Sun G (2014). Effects of short-term environmental hyperthermia on patterns of cerebral blood flow. Physiol Behav 128, 99-107.
    1. Reyna JL et al (2015). Arterial to end-tidal PCO2 difference during exercise in normoxia and severe acute hypoxia: importance of blood temperature correction. Physiol Rep 3, e12512.
    1. Robbins PA, Conway J, Cunningham DA, Khamnei S & Paterson DJ (1990). A comparison of indirect methods for continuous estimation of arterial PCO2 in men. J Appl Physiol 68, 1727-1731.
    1. Sato K, Ogoh S, Hirasawa A, Oue A & Sadamoto T (2011). The distribution of blood flow in the carotid and vertebral arteries during dynamic exercise in humans. J Physiol (Lond) 589, 2847-2856.
    1. Sato K, Oue A, Yoneya M, Sadamoto T & Ogoh S (2016). Heat stress redistributes blood flow in arteries of the brain during dynamic exercise. J Appl Physiol 120, 766-773.
    1. Sato K & Sadamoto T (2010). Different blood flow responses to dynamic exercise between internal carotid and vertebral arteries in women. J Appl Physiol 109, 864-869.
    1. Siemens J & Kamm GB (2018). Cellular populations and thermosensing mechanisms of the hypothalamic thermoregulatory center. Pflugers Arch 470, 809-822.
    1. Smith KJ & Ainslie PN (2017). Regulation of cerebral blood flow and metabolism during exercise. Exp Physiol 102, 1356-1371.
    1. Smith KJ, MacLeod D, Willie CK, Lewis NCS, Hoiland RL, Ikeda K, Tymko MM, Donnelly J, Day TA, MacLeod N, Lucas SJE & Ainslie PN (2014). Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery. J Physiol (Lond) 592, 5507-5527.
    1. Smith KJ, Wildfong KW, Hoiland RL, Harper M, Lewis NC, Pool A, Smith SL, Kuca T, Foster GE & Ainslie PN (2016). Role of CO2 in the cerebral hyperemic response to incremental normoxic and hyperoxic exercise. J Appl Physiol 120, 843-854.
    1. Szabo K, Lako E, Juhasz T, Rosengarten B, Csiba L & Olah L (2011). Hypocapnia induced vasoconstriction significantly inhibits the neurovascular coupling in humans. J Neurol Sci 309, 58-62.
    1. Thomas KN, Lewis NCS, Hill BG & Ainslie PN (2015). Technical recommendations for the use of carotid duplex ultrasound for the assessment of extracranial blood flow. Am J Physiol Regul Integr Comp Physiol 309, 1-7.
    1. Tsuji B, Filingeri D, Honda Y, Eguchi T, Fujii N, Kondo N & Nishiyasu T (2017). Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated humans. J Appl Physiol 124, 225-233.
    1. Tsuji B, Hoshi Y, Honda Y, Fujii N, Sasaki Y, Cheung SS, Kondo N & Nishiyasu T (2019). Respiratory mechanics and cerebral blood flow during heat-induced hyperventilation and its voluntary suppression in passively heated humans. Physiol Rep 7, e13967.
    1. Tymko MM, Ainslie PN, Macleod DB, Willie CK & Foster GE (2015). End tidal-to-arterial CO2 and O2 gas gradients at low- and high-altitude during dynamic end-tidal forcing. Am J Physiol Regul Integr Comp Physiol 308, R895-R906.
    1. Tymko MM, Hoiland RL, Kuca T, Boulet LM, Tremblay JC, Pinske BK, Williams AM & Foster GE (2016). Measuring the human ventilatory and cerebral blood flow response to CO2: a technical consideration for the end-tidal-to-arterial gas gradient. J Appl Physiol 120, 282-296.
    1. Verbree J, Bronzwaer A, van Buchem MA, Daemen M, van Lieshout JJ & van Osch M (2017). Middle cerebral artery diameter changes during rhythmic handgrip exercise in humans. J Cereb Blood Flow Metab 37, 2921-2927.
    1. Willie CK & Ainslie PN (2011). Cool head, hot brain: cerebral blood flow distribution during exercise. J Physiol (Lond) 589, 2657-2658.
    1. Willie CK, Colino FL, Bailey DM, Tzeng YC, Binsted G, Jones LW, Haykowsky MJ, Bellapart J, Ogoh S, Smith KJ, Smirl JD, Day TA, Lucas SJ, Eller LK & Ainslie PN (2011a). Utility of transcranial Doppler ultrasound for the integrative assessment of cerebrovascular function. J Neurosci Methods 196, 221-237.
    1. Willie CK, Cowan EC, Ainslie PN, Taylor CE, Smith KJ, Sin PYW & Tzeng YC (2011b). Neurovascular coupling and distribution of cerebral blood flow during exercise. J Neurosci Methods 198, 270-273.
    1. Willie CK, Macleod DB, Shaw AD, Smith KJ, Tzeng YC, Eves ND, Ikeda K, Graham J, Lewis NC, Day TA & Ainslie PN (2012). Regional brain blood flow in man during acute changes in arterial blood gases. J Physiol (Lond) 590, 3261-3275.
    1. Woodman RJ, Playford DA, Watts GF, Cheetham C, Reed C, Taylor RR, Puddey IB, Beilin LJ, Burke V, Mori TA & Green D (2001). Improved analysis of brachial artery ultrasound using a novel edge-detection software system. J Appl Physiol 91, 929-937.
    1. Yablonskiy DA, Ackerman JJH & Raichle ME (2000). Coupling between changes in human brain temperature and oxidative metabolism during prolonged visual stimulation. Proc Natl Acad Sci 97, 7603-7608.
    1. Yamaguchi Y, Ikemura T & Hayashi N (2015a). Exhaustive exercise attenuates the neurovascular coupling by blunting the pressor response to visual stimulation. Biomed Res Int 2015, 671063-671066.
    1. Yamaguchi Y, Ikemura T, Kashima H & Hayashi N (2015b). Effects of vasodilatation and pressor response on neurovascular coupling during dynamic exercise. Eur J Appl Physiol 115, 619-625.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir