Multiple Sclerosis Impairs Sweating but not Skin Blood Flow during a Passive Whole-Body Heat Stress

The venoarteriolar response (VAR) increases vascular resistance upon increases in venous transmural pressure in cutaneous, subcutaneous, and muscle vascular beds. During orthostasis, it has been proposed that up to 45% of the increase in systemic vascular tone is due to VAR-related local mechanism(s). The objective of this project was to test the hypothesis that heat stress attenuates VAR-mediated cutaneous and whole leg vasoconstriction. During normothermic conditions, measurements of cutaneous blood flow (laser-Doppler flowmetry) and femoral artery blood flow (Doppler ultrasound) were obtained from both legs during supine and leg-dependent conditions. These measurements were repeated following a whole body heat stress (increase in internal temperature of 1.4 ± 0.2°C). Before leg dependency, cutaneous (CVC) and femoral vascular conductances (FVC) were significantly elevated in both legs during heat stress relative to normothermia ( P < 0.001). During leg dependency the absolute decrease in CVC was attenuated during heat stress ( P < 0.01) while the absolute decrease in FVC was unaffected ( P = 0.90). When CVC and FVC data were analyzed as a relative change from their respective baseline values, heat stress significantly attenuated the magnitude of vasoconstriction due to leg dependency in the cutaneous and femoral circulations ( P < 0.001 for both variables). These data suggest that an attenuated local vasoconstriction, evoked via the venoarteriolar response, may contribute to reduced blood pressure control and thus reduced orthostatic tolerance that occurs in heat-stressed individuals.

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Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00702.2010 ◽

2011 ◽

Vol 110 (5) ◽

pp. 1406-1413 ◽

Cited By ~ 18

Author(s):

Dean L. Kellogg ◽

Joan L. Zhao ◽

Yubo Wu ◽

John M. Johnson

Keyword(s):

Blood Flow ◽

Heat Stress ◽

Guanylyl Cyclase ◽

Soluble Guanylyl Cyclase ◽

Whole Body ◽

Local Skin ◽

Cutaneous Vasodilation ◽

Local Skin Temperature ◽

Whole Body Heat Stress ◽

Body Heat

We hypothesized that nitric oxide activation of soluble guanylyl cyclase (sGC) participates in cutaneous vasodilation during whole body heat stress and local skin warming. We examined the effects of the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on reflex skin blood flow responses to whole body heat stress and on nonreflex responses to increased local skin temperature. Blood flow was monitored by laser-Doppler flowmetry, and blood pressure by Finapres to calculate cutaneous vascular conductance (CVC). Intradermal microdialysis was used to treat one site with 1 mM ODQ in 2% DMSO and Ringer, a second site with 2% DMSO in Ringer, and a third site received Ringer. In protocol 1, after a period of normothermia, whole body heat stress was induced. In protocol 2, local heating units warmed local skin temperature from 34 to 41°C to cause local vasodilation. In protocol 1, in normothermia, CVC did not differ among sites [ODQ, 15 ± 3% maximum CVC (CVCmax); DMSO, 14 ± 3% CVCmax; Ringer, 17 ± 6% CVCmax; P > 0.05]. During heat stress, ODQ attenuated CVC increases (ODQ, 54 ± 4% CVCmax; DMSO, 64 ± 4% CVCmax; Ringer, 63 ± 4% CVCmax; P < 0.05, ODQ vs. DMSO or Ringer). In protocol 2, at 34°C local temperature, CVC did not differ among sites (ODQ, 17 ± 2% CVCmax; DMSO, 18 ± 4% CVCmax; Ringer, 18 ± 3% CVCmax; P > 0.05). ODQ attenuated CVC increases at 41°C local temperature (ODQ, 54 ± 5% CVCmax; DMSO, 86 ± 4% CVCmax; Ringer, 90 ± 2% CVCmax; P < 0.05 ODQ vs. DMSO or Ringer). sGC participates in neurogenic active vasodilation during heat stress and in the local response to direct skin warming.

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Local heating, but not indirect whole body heating, increases human skeletal muscle blood flow

Journal of Applied Physiology ◽

10.1152/japplphysiol.00269.2011 ◽

2011 ◽

Vol 111 (3) ◽

pp. 818-824 ◽

Cited By ~ 83

Author(s):

Ilkka Heinonen ◽

R. Matthew Brothers ◽

Jukka Kemppainen ◽

Juhani Knuuti ◽

Kari K. Kalliokoski ◽

...

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Heat Stress ◽

Local Heating ◽

Muscle Blood Flow ◽

Whole Body ◽

Skeletal Muscle Blood Flow ◽

Whole Body Heat Stress ◽

Body Heat ◽

Indirect Heating

For decades it was believed that direct and indirect heating (the latter of which elevates blood and core temperatures without directly heating the area being evaluated) increases skin but not skeletal muscle blood flow. Recent results, however, suggest that passive heating of the leg may increase muscle blood flow. Using the technique of positron-emission tomography, the present study tested the hypothesis that both direct and indirect heating increases muscle blood flow. Calf muscle and skin blood flows were evaluated from eight subjects during normothermic baseline, during local heating of the right calf [only the right calf was exposed to the heating source (water-perfused suit)], and during indirect whole body heat stress in which the left calf was not exposed to the heating source. Local heating increased intramuscular temperature of the right calf from 33.4 ± 1.0°C to 37.4 ± 0.8°C, without changing intestinal temperature. This stimulus increased muscle blood flow from 1.4 ± 0.5 to 2.3 ± 1.2 ml·100 g−1·min−1 ( P < 0.05), whereas skin blood flow under the heating source increased from 0.7 ± 0.3 to 5.5 ± 1.5 ml·100 g−1·min−1 ( P < 0.01). While whole body heat stress increased intestinal temperature by ∼1°C, muscle blood flow in the calf that was not directly exposed to the water-perfused suit (i.e., indirect heating) did not increase during the whole body heat stress (normothermia: 1.6 ± 0.5 ml·100 g−1·min−1; heat stress: 1.7 ± 0.3 ml·100 g−1·min−1; P = 0.87). Whole body heating, however, reflexively increased calf skin blood flow (to 4.0 ± 1.5 ml·100 g−1·min−1) in the area not exposed to the water-perfused suit. These data show that local, but not indirect, heating increases calf skeletal muscle blood flow in humans. These results have important implications toward the reconsideration of previously accepted blood flow distribution during whole body heat stress.

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Impaired sweating responses to a passive whole body heat stress in individuals with multiple sclerosis

Journal of Neurophysiology ◽

10.1152/jn.00897.2016 ◽

2017 ◽

Vol 118 (1) ◽

pp. 7-14 ◽

Cited By ~ 9

Author(s):

Dustin R. Allen ◽

Mu Huang ◽

Iqra M. Parupia ◽

Ariana R. Dubelko ◽

Elliot M. Frohman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Heat Stress ◽

Core Temperature ◽

Sweat Rate ◽

Whole Body ◽

Healthy Controls ◽

Cutaneous Vasodilation ◽

Whole Body Heat Stress ◽

Reflex Control ◽

Body Heat

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), disrupting autonomic function. The aim of this study was to test the hypothesis that individuals with MS have blunted control of thermoregulatory reflex increases in sweat rate (SR) and cutaneous vasodilation compared with controls during a passive whole body heat stress (WBH). Eighteen individuals with relapsing-remitting MS and 18 healthy controls (Con) participated in the study. Core temperature (Tcore), skin temperature, heart rate, arterial blood pressure (10-min intervals), skin blood flow (laser-Doppler flux, LDF), and SR were continuously measured during normothermic baseline (34°C water perfusing a tube-lined suit) and WBH (increased Tcore 0.8°C via 48°C water perfusing the suit). Following WBH, local heaters were warmed to 42°C, inducing peak cutaneous vasodilation at the site of LDF collection. Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to mean arterial pressure and expressed as a percentage of peak achieved during local heating. Individuals with MS had attenuated SR responses to WBH (ΔSR from baseline: Con, 0.65 ± 0.27; MS, 0.42 ± 0.17 mg·cm−2·min−1, P = 0.003), whereas Δ%CVC42C from baseline was similar between groups (Con, 42 ± 16%; MS, 38 ± 12%, P = 0.39). SR responses were blunted as a function of Tcore in MS (interaction: group × Tcore, P = 0.03), of which differences were evident at ΔTcore 0.7°C and 0.8°C ( P < 0.05). No interaction was observed in Δ%CVC42C. Taken together, the findings show MS blunts sweating responses, whereas control of the cutaneous vasculature is preserved, in response to WBH. NEW & NOTEWORTHY This study is the first to assess the reflex control of the thermoregulatory system in individuals living with multiple sclerosis (MS). The novel findings are twofold. First, attenuated increases in sweat rate in subjects with MS compared with healthy controls were observed in response to a moderate increase (0.8°C) in core temperature via passive whole body heat stress. Second, it appears the reflex control of the cutaneous vasculature is preserved in MS.

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Temperature and blood flow distribution in the human leg during passive heat stress

Journal of Applied Physiology ◽

10.1152/japplphysiol.00965.2015 ◽

2016 ◽

Vol 120 (9) ◽

pp. 1047-1058 ◽

Cited By ~ 23

Author(s):

Scott T. Chiesa ◽

Steven J. Trangmar ◽

José González-Alonso

Keyword(s):

Blood Flow ◽

Heat Stress ◽

Femoral Vein ◽

Flow Distribution ◽

Whole Body ◽

Temperature Sensitive ◽

Young Males ◽

Arterial Blood ◽

Whole Body Heat Stress ◽

Body Heat

The influence of temperature on the hemodynamic adjustments to direct passive heat stress within the leg's major arterial and venous vessels and compartments remains unclear. Fifteen healthy young males were tested during exposure to either passive whole body heat stress to levels approaching thermal tolerance [core temperature (Tc) + 2°C; study 1; n = 8] or single leg heat stress (Tc + 0°C; study 2; n = 7). Whole body heat stress increased perfusion and decreased oscillatory shear index in relation to the rise in leg temperature (Tleg) in all three major arteries supplying the leg, plateauing in the common and superficial femoral arteries before reaching severe heat stress levels. Isolated leg heat stress increased arterial blood flows and shear patterns to a level similar to that obtained during moderate core hyperthermia (Tc + 1°C). Despite modest increases in great saphenous venous (GSV) blood flow (0.2 l/min), the deep venous system accounted for the majority of returning flow (common femoral vein 0.7 l/min) during intense to severe levels of heat stress. Rapid cooling of a single leg during severe whole body heat stress resulted in an equivalent blood flow reduction in the major artery supplying the thigh deep tissues only, suggesting central temperature-sensitive mechanisms contribute to skin blood flow alone. These findings further our knowledge of leg hemodynamic responses during direct heat stress and provide evidence of potentially beneficial vascular alterations during isolated limb heat stress that are equivalent to those experienced during exposure to moderate levels of whole body hyperthermia.

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Hemodynamic responses to heat stress in the resting and exercising human leg: insight into the effect of temperature on skeletal muscle blood flow

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00662.2010 ◽

2011 ◽

Vol 300 (3) ◽

pp. R663-R673 ◽

Cited By ~ 70

Author(s):

James Pearson ◽

David A. Low ◽

Eric Stöhr ◽

Kameljit Kalsi ◽

Leena Ali ◽

...

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Heat Stress ◽

Tissue Oxygenation ◽

Muscle Blood Flow ◽

Whole Body ◽

Muscle Temperature ◽

Whole Body Heat Stress ◽

Arterial Plasma ◽

Body Heat

Heat stress increases limb blood flow and cardiac output (Q̇) in humans, presumably in sole response to an augmented thermoregulatory demand of the skin circulation. Here we tested the hypothesis that local hyperthermia also increases skeletal muscle blood flow at rest and during exercise. Hemodynamics, blood and tissue oxygenation, and muscle, skin, and core temperatures were measured at rest and during exercise in 11 males across four conditions of progressive whole body heat stress and at rest during isolated leg heat stress. During whole body heat stress, leg blood flow (LBF), Q̇, and leg (LVC) and systemic vascular conductance increased gradually with elevations in muscle temperature both at rest and during exercise ( r2 = 0.86–0.99; P < 0.05). Enhanced LBF and LVC were accompanied by reductions in leg arteriovenous oxygen (a-vO2) difference and increases in deep femoral venous O2 content and quadriceps tissue oxygenation, reflecting elevations in muscle and skin perfusion. The increase in LVC occurred despite an augmented plasma norepinephrine ( P < 0.05) and was associated with elevations in muscle temperature ( r2 = 0.85; P = 0.001) and arterial plasma ATP ( r2 = 0.87; P < 0.001). Isolated leg heat stress accounted for one-half of the increase in LBF with severe whole body heat stress. Our findings suggest that local hyperthermia also induces vasodilatation of the skeletal muscle microvasculature, thereby contributing to heat stress and exercise hyperemia. The increased limb muscle vasodilatation in these conditions of elevated muscle sympathetic vasoconstrictor activity is closely related to the rise in arterial plasma ATP and local tissue temperature.

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Heat Stress and Cardiovascular, Hormonal, and Heat Shock Proteins in Humans

Journal of Athletic Training ◽

10.4085/1062-6050-47.2.184 ◽

2012 ◽

Vol 47 (2) ◽

pp. 184-190 ◽

Cited By ~ 38

Author(s):

Masaki Iguchi ◽

Andrew E. Littmann ◽

Shuo-Hsiu Chang ◽

Lydia A. Wester ◽

Jane S. Knipper ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Heat Stress ◽

Heat Shock ◽

Body Temperature ◽

Controlled Trial ◽

Whole Body ◽

Cord Injury ◽

Whole Body Heat Stress ◽

Body Heat

Context: Conditions such as osteoarthritis, obesity, and spinal cord injury limit the ability of patients to exercise, preventing them from experiencing many well-documented physiologic stressors. Recent evidence indicates that some of these stressors might derive from exercise-induced body temperature increases. Objective: To determine whether whole-body heat stress without exercise triggers cardiovascular, hormonal, and extra-cellular protein responses of exercise. Design: Randomized controlled trial. Setting: University research laboratory. Patients or Other Participants: Twenty-five young, healthy adults (13 men, 12 women; age = 22.1 ± 2.4 years, height = 175.2 ± 11.6 cm, mass = 69.4 ± 14.8 kg, body mass index = 22.6 ± 4.0) volunteered. Intervention(s): Participants sat in a heat stress chamber with heat (73°C) and without heat (26°C) stress for 30 minutes on separate days. We obtained blood samples from a subset of 13 participants (7 men, 6 women) before and after exposure to heat stress. Main Outcome Measure(s): Extracellular heat shock protein (HSP72) and catecholamine plasma concentration, heart rate, blood pressure, and heat perception. Results: After 30 minutes of heat stress, body temperature measured via rectal sensor increased by 0.8°C. Heart rate increased linearly to 131.4 ± 22.4 beats per minute (F6,24 = 186, P < .001) and systolic and diastolic blood pressure decreased by 16 mm Hg (F6,24 = 10.1, P < .001) and 5 mm Hg (F6,24 = 5.4, P < .001), respectively. Norepinephrine (F1,12 = 12.1, P = .004) and prolactin (F1,12 = 30.2, P < .001) increased in the plasma (58% and 285%, respectively) (P < .05). The HSP72 (F1,12 = 44.7, P < .001) level increased with heat stress by 48.7% ± 53.9%. No cardiovascular or blood variables showed changes during the control trials (quiet sitting in the heat chamber with no heat stress), resulting in differences between heat and control trials. Conclusions: We found that whole-body heat stress triggers some of the physiologic responses observed with exercise. Future studies are necessary to investigate whether carefully prescribed heat stress constitutes a method to augment or supplement exercise.

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Carotid baroreflex control of heart rate is enhanced during whole‐body heat stress

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.1118.33 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Davor Krnjajic ◽

Cory L Butts ◽

W Shane Warren ◽

Mitchel R Samels ◽

David M Keller

Keyword(s):

Heart Rate ◽

Heat Stress ◽

Whole Body ◽

Baroreflex Control ◽

Carotid Baroreflex ◽

Whole Body Heat Stress ◽

Body Heat

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Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by local warming of the skin and whole body heat stress in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00690.2009 ◽

2009 ◽

Vol 107 (5) ◽

pp. 1438-1444 ◽

Cited By ~ 90

Author(s):

Dean L. Kellogg ◽

Joan L. Zhao ◽

Yubo Wu

Keyword(s):

Nitric Oxide ◽

Heat Stress ◽

No Synthase ◽

Whole Body ◽

Doppler Flowmetry ◽

Vasodilator Response ◽

Cutaneous Vasodilation ◽

Forearm Skin ◽

Whole Body Heat Stress ◽

Body Heat

Nitric oxide (NO) participates in the cutaneous vasodilation caused by increased local skin temperature (Tloc) and whole body heat stress in humans. In forearm skin, endothelial NO synthase (eNOS) participates in vasodilation due to elevated Tloc and neuronal NO synthase (nNOS) participates in vasodilation due to heat stress. To explore the relative roles and interactions of these isoforms, we examined the effects of a relatively specific eNOS inhibitor, Nω-amino-l-arginine (LNAA), and a specific nNOS inhibitor, Nω-propyl-l-arginine (NPLA), both separately and in combination, on skin blood flow (SkBF) responses to increased Tloc and heat stress in two protocols. In each protocol, SkBF was monitored by laser-Doppler flowmetry (LDF) and mean arterial pressure (MAP) by Finapres. Cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Intradermal microdialysis was used to treat one site with 5 mM LNAA, another with 5 mM NPLA, a third with combined 5 mM LNAA and 5 mM NPLA (Mix), and a fourth site with Ringer only. In protocol 1, Tloc was controlled with combined LDF/local heating units. Tloc was increased from 34°C to 41.5°C to cause local vasodilation. In protocol 2, after a period of normothermia, whole body heat stress was induced (water-perfused suits). At the end of each protocol, all sites were perfused with 58 mM nitroprusside to effect maximal vasodilation for data normalization. In protocol 1, at Tloc = 34°C, CVC did not differ between sites ( P > 0.05). LNAA and Mix attenuated CVC increases at Tloc = 41.5°C to similar extents ( P < 0.05, LNAA or Mix vs. untreated or NPLA). In protocol 2, in normothermia, CVC did not differ between sites ( P > 0.05). During heat stress, NPLA and Mix attenuated CVC increases to similar extents, but no significant attenuation occurred with LNAA ( P < 0.05, NPLA or Mix vs. untreated or LNAA). In forearm skin, eNOS mediates the vasodilator response to increased Tloc and nNOS mediates the vasodilator response to heat stress. The two isoforms do not appear to interact during either response.

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