Publications by authors named "Howard Carter"

56 Publications

The Impact of Six-Month Land versus Water Walking on Cerebrovascular Function in the Aging Brain.

Med Sci Sports Exerc 2021 Apr 15. Epub 2021 Apr 15.

School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, WA, Australia Medical School, University of Western Australia, Perth, WA, Australia Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia North Western Mental Health, Melbourne Health, Melbourne, VIC Australia School of Psychological Science, University of Western Australia, Perth, WA, Australia Centre for Heart, Lung and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, British Columbia, Canada.

Introduction: To examine the hypothesis that exercise training induces adaptation in cerebrovascular function, we recruited 63 older adults (62±7 yrs, 46 females), to undertake 24 weeks of either land-walking, water-walking, or participate in a non-exercise control group. This is the first multi-interventional study to perform a comprehensive assessment of cerebrovascular function in response to longer term (6-month) training interventions, including water-based exercise, in older healthy individuals.

Methods: Intra-cranial blood flow velocities (middle [MCAv] and posterior [PCAv] cerebral arteries) were assessed at rest, and in response to neurovascular coupling, hypercapnic reactivity and cerebral autoregulation.

Results: We observed no change in resting MCAv in response to either training intervention (pre v post, mean [95% confidence interval], land-walking: 65 [59-70] to 63 [57-68] cm/s, P=0.33 and water-walking: 63 [58-69] to 61 [55-67] cm/s, P=0.92) compared to controls, and no change in neurovascular coupling (land-walking: P=0.18, water-walking: P=0.17). There was a significant but modest improvement in autoregulatory normalised gain following the intervention in the water-walking compared to the land-walking group (P=0.03). Hypercapnic MCAv reactivity was not different based on exercise group (land: P=087, water: P=0.83); however, when data were pooled from the exercise groups, increases in fitness were correlated with decreases in hypercapnic reactivity (r2=0.25, P=0.003).

Conclusion: While exercise was not associated with systematic changes across multiple domains of cerebrovascular function, our data indicate that exercise may induce modest changes in autoregulation and CO2 reactivity. These findings should encourage further studies of the longer term implications of exercise training on cerebrovascular health.
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http://dx.doi.org/10.1249/MSS.0000000000002685DOI Listing
April 2021

A High Activity Level Is Required for Augmented Muscle Capillarization in Older Women.

Med Sci Sports Exerc 2021 May;53(5):894-903

Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, DENMARK.

Purpose: This study aimed to evaluate the influence of lifelong regular physical activity on skeletal muscle capillarization in women.

Methods: Postmenopausal women, 61±4 yr old, were divided according to self-reported physical activity level over the past 20 yrs: sedentary (SED; n = 14), moderately active (MOD; n = 12), and very active (VERY; n = 15). Leg blood flow (LBF) was determined by ultrasound Doppler, and blood samples were drawn from the femoral artery and vein for calculation of leg oxygen uptake (LVO2) at rest and during one-legged knee extensor exercise. A skeletal muscle biopsy was obtained from the vastus lateralis and analyzed for capillarization and vascular endothelial growth factor (VEGF) and mitochondrial OXPHOS proteins. Platelets were isolated from venous blood and analyzed for VEGF content and effect on endothelial cell proliferation.

Results: The exercise-induced rise in LBF and LVO2 was faster (P = 0.008) in VERY compared with SED and MOD. Steady-state LBF and LVO2 were lower (P < 0.04) in MOD and VERY compared with SED. Capillary-fiber ratio and capillary density were greater (P < 0.03) in VERY (1.65 ± 0.48 and 409.3 ± 57.5) compared with MOD (1.30 ± 0.19 and 365.0 ± 40.2) and SED (1.30 ± 0.30 and 356.2 ± 66.3). Skeletal muscle VEGF and OXPHOS complexes I, II, and V were ~1.6-fold and ~1.25-fold (P < 0.01) higher, respectively, in VERY compared with SED. Platelets from all groups induced an approximately nine-fold (P < 0.001) increase in endothelial cell proliferation.

Conclusion: A very active lifestyle is associated with superior skeletal muscle exercise hemodynamics and greater potential for oxygen extraction concurrent with a higher skeletal muscle capillarization and mitochondrial capacity.
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http://dx.doi.org/10.1249/MSS.0000000000002566DOI Listing
May 2021

The Impact of Lower Limb Immobilization and Rehabilitation on Angiogenic Proteins and Capillarization in Skeletal Muscle.

Med Sci Sports Exerc 2021 Mar 25. Epub 2021 Mar 25.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark Technical University of Munich, Germany. Sylvia Lawry Centre for Multiple Sclerosis Research, Munich, Germany.

Purpose: Skeletal muscle vascularization is important for tissue regeneration after injury and immobilization. We examined whether complete immobilization influences capillarization and oxygen delivery to the muscle and assessed the efficacy of rehabilitation by aerobic exercise training.

Methods: Young healthy males had one leg immobilized for 14 days and subsequently completed four weeks of intense aerobic exercise training. Biopsies were obtained from m.vastus lateralis and a-v blood sampling for assessment of oxygen extraction and leg blood flow during exercise was done before and after immobilization and training. Muscle capillarization, muscle and platelet content of vascular endothelial growth factor (VEGF) and muscle thrombospondin-1 were determined.

Results: Immobilization did not have a significant impact on capillary per fiber ratio or capillary density. The content of VEGF protein in muscle samples was reduced by 36% (P=0.024) and VEGF to thrombospondin-1 ratio was 94 % lower (P=0.046). The subsequent four-week training period increased the muscle VEGF content and normalized the muscle VEGF to thrombospondin-1 ratio but did not influence capillarization. Platelet VEGF content followed the trend of muscle VEGF. At the functional level, oxygen extraction, blood flow and oxygen delivery at rest and during submaximal exercise were not affected by immobilization or training.

Conclusion: The results demonstrate that just two weeks of leg immobilization leads to a strongly reduced angiogenic potential as evidenced by reduced muscle and platelet VEGF content and a reduced muscle VEGF to thrombospondin-1 ratio. Moreover, a subsequent period of intensive aerobic exercise training fails to increase capillarization in the previously immobilized leg, possibly due to the angiostatic condition caused by immobilization.
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http://dx.doi.org/10.1249/MSS.0000000000002665DOI Listing
March 2021

Adaptation to Exercise Training in Conduit Arteries and Cutaneous Microvessels in Humans: An Optical Coherence Tomography Study.

Med Sci Sports Exerc 2021 Mar 12. Epub 2021 Mar 12.

Physiology Department, Faculty of Medicine, Airlangga University, Surabaya, Indonesia Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia Integrative Physiology Laboratory, Department of Kinesiology and Nutrition, College of Health Sciences, The University of Illinois, Chicago, IL Australian Research Council Centre of Excellence for Nanoscale Biophotonics, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia Institute for Photonics and Advanced Sensing, The University of Adelaide, Adelaide, Australia School of Electrical, Electronic and Computer Engineering, The University of Western Australia, Perth, Australia.

Introduction: Exercise training has anti-atherogenic impacts on conduit and resistance artery function and structure in humans and induces angiogenic changes in skeletal muscle. However, training-induced adaptation in cutaneous microvessels is poorly understood, partly due to technological limitations. Optical coherence tomography (OCT) is a novel high resolution imaging technique capable of visualising cutaneous microvasculature at a resolution of ~30μm. We utilised OCT to visualise the impacts of training on cutaneous microvessels, alongside assessment of conduit artery flow mediated dilation (FMD).

Methods: We assessed brachial FMD and cutaneous microcirculatory responses at rest and in response to local heating and reactive hyperaemia; pre- and post-training in 8 healthy men compared to age-matched untrained controls (n=8). Participants in the training group underwent supervised cycling at 80% HRmax, 3x/week for 8 weeks.

Results: We found a significant interaction (P=0.04), whereby increase in FMD was observed after training (post 9.83±3.27 % vs pre 6.97±1.77 %, P=0.01), with this post training value higher compared to control group (6.9±2.87 %, P=0.027). FMD was not altered in the controls (P=0.894). There was a significant interaction for OCT-derived speed (P=0.038) whereby a significant decrease in the local disc heating response was observed after training (post 98.6±3.9 μm.sec-1 vs pre 102±5 μm.sec-1, P=0.012), whilst no changes was observed for OCT-derived speed in the control group (P=0.877). Other OCT responses (diameter, flow-rate and density) to local heating and reactive hyperaemia were unaffected by training.

Conclusions: Our findings suggest that vascular adaptation to exercise training is not uniform across all levels of the arterial tree; while exercise training improves larger artery function, this was not accompanied by unequivocal evidence for cutaneous microvascular adaptation in young healthy subjects.
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http://dx.doi.org/10.1249/MSS.0000000000002654DOI Listing
March 2021

Can exercise training enhance the repeated remote ischaemic preconditioning stimulus on peripheral and cerebrovascular function in high-risk individuals?

Eur J Appl Physiol 2021 Apr 28;121(4):1167-1178. Epub 2021 Jan 28.

Research Institute of Sports and Exercise Science, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool, L3 3AF, UK.

Background: Repeated exposure to remote ischaemic preconditioning (rIPC; short bouts of non-lethal ischaemia) enhances peripheral vascular function within 1 week; whereas, longer periods of rIPC (~ 1 year) may improve cerebral perfusion. Increasing the 'dose' of rIPC may lead to superior effects. Given the similarities between exercise and rIPC, we examined whether adding exercise to the rIPC stimulus leads to greater adaptation in systemic vascular function.

Methods: Nineteen individuals with increased risk for cardiovascular disease (CVD) were randomly allocated to either 8 weeks of rIPC (n = 9) or 8 weeks of rIPC + exercise (rIPC + Ex) (n = 10). rIPC was applied three times per week in both conditions, and exercise consisted of 50 min (70% heart rate max) of cycling 3 times per week. Peripheral endothelial function was assessed using flow-mediated dilation (FMD) before and after ischaemia-reperfusion (IR). Cerebrovascular function was assessed by dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity (CVR), and cardio-respiratory fitness (VO) using a maximal aerobic capacity test.

Results: FMD% increased by 1.6% (95% CI, 0.4, 2.8) following rIPC + Ex and by 0.3% (- 1.1, 1.5) in the only rIPC but this did not reach statistical significance (P = 0.65). Neither intervention evoked a change in dCA or in CVR (P > 0.05). VO increased by 2.8 ml/kg/min (1.7, 3.9) following the rIPC + Ex and by 0.1 ml/kg/min (- 1.0, 1.4) following the rIPC only intervention (P = 0.69).

Conclusion: Combining exercise with rIPC across an 8-week intervention does not lead to superior effects in cerebrovascular and peripheral vascular function compared to a repeated rIPC intervention in individuals at risk of CVD.
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http://dx.doi.org/10.1007/s00421-020-04580-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966185PMC
April 2021

Visualizing and quantifying cutaneous microvascular reactivity in humans by use of optical coherence tomography: impaired dilator function in diabetes.

Am J Physiol Endocrinol Metab 2020 11 21;319(5):E923-E931. Epub 2020 Sep 21.

Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia.

The pathophysiology and time course of impairment in cutaneous microcirculatory function and structure remain poorly understood in people with diabetes, partly due to the lack of investigational tools capable of directly imaging and quantifying the microvasculature in vivo. We applied a new optical coherence tomography (OCT) technique, at rest and during reactive hyperemia (RH), to assess the skin microvasculature in people with diabetes with foot ulcers (DFU, = 13), those with diabetes without ulcers (DNU, = 9), and matched healthy controls (CON, = 13). OCT images were obtained from the dorsal part of the foot at rest and following 5 min of local ischemia induced by inflating a cuff around the thigh at suprasystolic level (220 mmHg). One-way ANOVA was used to compare the OCT-derived parameters (diameter, speed, flow rate, and density) at rest and in response to RH, with repeated-measures two-way ANOVA performed to analyze main and interaction effects between groups. Data are means ± SD. At rest, microvascular diameter in the DFU (84.89 ± 14.84 µm) group was higher than CON (71.25 ± 7.6 µm, = 0.012) and DNU (71.33 ± 12.04 µm, = 0.019) group. Speed in DFU (65.56 ± 4.80 µm/s, = 0.002) and DNU (63.22 ± 4.35 µm/s, = 0.050) were higher than CON (59.58 ± 3.02 µm/s). Microvascular density in DFU (22.23 ± 13.8%) was higher than in CON (9.83 ± 2.94%, = 0.008), but not than in the DNU group (14.8 ± 10.98%, = 0.119). All OCT-derived parameters were significantly increased in response to RH in the CON group (all < 0.01) and DNU group (all < 0.05). Significant increase in the DFU group was observed in speed ( = 0.031) and density ( = 0.018). The change in density was lowest in the DFU group (44 ± 34.1%) compared with CON (199.2 ± 117.5%, = 0.005) and DNU (148.1 ± 98.4, = 0.054). This study proves that noninvasive OCT microvascular imaging is feasible in people with diabetes, provides powerful new physiological insights, and can distinguish between healthy individuals and patients with diabetes with distinct disease severity.
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http://dx.doi.org/10.1152/ajpendo.00233.2020DOI Listing
November 2020

Optical coherence tomography: a novel imaging approach to visualize and quantify cutaneous microvascular structure and function in patients with diabetes.

BMJ Open Diabetes Res Care 2020 08;8(1)

Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Crawley, Western Australia, Australia

Introduction: The pathophysiology of microvascular disease is poorly understood, partly due to the lack of tools to directly image microvessels in vivo.

Research Design And Methods: In this study, we deployed a novel optical coherence tomography (OCT) technique during local skin heating to assess microvascular structure and function in diabetics with (DFU group, n=13) and without (DNU group, n=10) foot ulceration, and healthy controls (CON group, n=13). OCT images were obtained from the dorsal foot, at baseline (33°C) and 30 min following skin heating.

Results: At baseline, microvascular density was higher in DFU compared with CON (21.9%±11.5% vs 14.3%±5.6%, p=0.048). Local heating induced significant increases in diameter, speed, flow rate and density in all groups (all p<0.001), with smaller changes in diameter for the DFU group (94.3±13.4 µm), compared with CON group (115.5±11.7 µm, p<0.001) and DNU group (106.7±12.1 µm, p=0.014). Heating-induced flow rate was lower in the DFU group (584.3±217.0 pL/s) compared with the CON group (908.8±228.2 pL/s, p<0.001) and DNU group (768.8±198.4 pL/s, p=0.014), with changes in density also lower in the DFU group than CON group (44.7%±15.0% vs 56.5%±9.1%, p=0.005).

Conclusions: This proof of principle study indicates that it is feasible to directly visualize and quantify microvascular function in people with diabetes; and distinguish microvascular disease severity between patients.
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http://dx.doi.org/10.1136/bmjdrc-2020-001479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451490PMC
August 2020

Ischemic Preconditioning Improves Microvascular Endothelial Function in Remote Vasculature by Enhanced Prostacyclin Production.

J Am Heart Assoc 2020 08 29;9(15):e016017. Epub 2020 Jul 29.

Section of Integrative Physiology Department of Nutrition, Exercise and Sports University of Copenhagen Denmark.

BACKGROUND The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. METHODS AND RESULTS A total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand-grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced (<0.05) the remote vasodilator response to intra-arterial acetylcholine in the leg at 5 and 90 minutes after application. The enhanced response was associated with a 6-fold increase (<0.05) in femoral venous plasma prostacyclin levels and with a transient increase (<0.05) in arterial plasma levels of brain-derived neurotrophic factor and vascular endothelial growth factor. In contrast, hand-grip exercise did not influence remote microvascular function. CONCLUSIONS These findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral-mediated potentiation of prostacyclin formation.
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http://dx.doi.org/10.1161/JAHA.120.016017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792245PMC
August 2020

Effects of Land versus Water Walking Interventions on Vascular Function in Older Adults.

Med Sci Sports Exerc 2021 01;53(1):83-89

School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, WA, AUSTRALIA.

Purpose: Endothelial dysfunction is an early and integral atherogenic event. Interventions that improve endothelial function also reduce cardiovascular risk. Due largely to the direct hemodynamic effects of repetitive exercise on the artery wall, exercise training has shown to enhance endothelial function. Land walking (LW) and water walking (WW) induce distinct hemodynamic responses, so the comparison of their effects provides an approach to study shear stress effects on endothelial function. We hypothesized that LW and WW training would have different effects on peripheral artery endothelial function.

Methods: Fifty-one sedentary, older (age = 61.9 ± 6.6 yr, 23.5% male) individuals were randomized into one of three groups: control (n = 16), or one of two exercise groups consisting of 3 × 50 min supervised and individually tailored walking sessions per week for 24 consecutive weeks, performed either on LW (n = 17) or on WW (n = 18). Brachial artery endothelial function (flow-mediated dilation) and smooth muscle cell function (glyceryl trinitrate administration) were tested in all participants before (week 0) and after (week 24) the intervention.

Results: Differences were apparent in flow-mediated dilation change between the LW group (week 0, 5.39% ± 0.71%, to week 24, 7.77% ± 0.78%; P = 0.009) and the control group (week 0, 5.87% ± 0.73%, to week 24, 5.78% ± 0.78%). No differences in artery dilation response were found after glyceryl trinitrate administration (all P > 0.05).

Conclusion: This study suggests that 6-month center-based LW may be superior to WW in terms of improvement in arterial endothelial function in older sedentary individuals.
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http://dx.doi.org/10.1249/MSS.0000000000002439DOI Listing
January 2021

Microvascular Function Is Impaired after Short-Term Immobilization in Healthy Men.

Med Sci Sports Exerc 2020 10;52(10):2107-2116

Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, DENMARK.

Purpose: We examined whether 2 wk of one-leg immobilization would impair leg microvascular function and to what extent a subsequent period of intense aerobic cycle training could restore function.

Methods: Study participants were healthy young men (n = 12; 20-24 yr of age). Leg microvascular function was determined before the intervention, after the immobilization period, and after a 4-wk exercise training period. Microvascular function was assessed as the vasodilator response to intra-arterial infusion of acetylcholine and sodium nitroprusside and as the vasoconstrictor response to endogenous noradrenaline release induced by tyramine infusion. Vasodilator enzymes as well as prooxidant and antioxidant enzymes were assessed by protein analysis in skeletal muscle samples: endothelial nitric oxide synthase, NADPH oxidase (NOX p67 and NOX gp91), and superoxide dismutase 2 (SOD2).

Results: The acetylcholine-induced change in vascular conductance was reduced after the 2 wk of immobilization (P = 0.003), tended to increase (P = 0.061), and was back to baseline levels after the subsequent 4 wk of exercise training. Plasma prostacyclin levels in response to acetylcholine infusion were lower after immobilization than before (P = 0.041). The changes in vascular conductance with sodium nitroprusside and tyramine were similar during all conditions. Skeletal muscle protein levels of endothelial nitric oxide synthase in the experimental leg were unchanged with immobilization and subsequent training but increased 47% in the control leg with training (P = 0.002). NOX p67, NOX gp91, and SOD2 in the experimental leg remained unaltered with immobilization, and SOD2 was higher than preimmobilization after 4 wk of training (P < 0.001).

Conclusions: The study shows that 2 wk of immobilization impairs leg microvascular endothelial function and prostacyclin formation but that 4 wk of intense aerobic exercise training restores the function. The underlying mechanism may reside in the prostacyclin system.
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http://dx.doi.org/10.1249/MSS.0000000000002369DOI Listing
October 2020

Land-walking vs. water-walking interventions in older adults: Effects on aerobic fitness.

J Sport Health Sci 2020 05 23;9(3):274-282. Epub 2019 Dec 23.

School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, WA 6009, Australia. Electronic address:

Background: Low cardiorespiratory fitness is an independent predictor of all-cause and cardiovascular mortality, and interventions that increase fitness reduce risk. Water-walking decreases musculoskeletal impact and risk of falls in older individuals, but it is unclear whether water-walking improves aerobic fitness in the same way as weight-dependent land-walking. This randomized controlled trial involved 3 intervention groups-a no-exercise control group (CG), a land-walking (LW) group, and a water-walking (WW) group-to investigate the comparative impacts of LW and WW to CG on fitness.

Methods: Both exercise groups attended individually tailored, center-based, intensity-matched 3 × weekly sessions for 24 weeks, which progressed to 150 min of exercise per week. This was followed by a 24-week no-intervention period. Maximal graded exercise tests were performed on a treadmill at Weeks 0, 24, and 48.

Results: Maximal oxygen uptake increased from Week 0 to Week 24 in both exercise groups (0.57 ± 0.62 mL/kg/min, 0.03 ± 0.04 L/min for LW; 0.93 ± 0.75 mL/kg/min, 0.06 ± 0.06 L/min for WW, mean ± SE) compared to the CG (-1.75 ± 0.78 mL/kg/min, -0.16 ± 0.05 L/min) (group × time, p < 0.05). Time to exhaustion increased significantly following LW only (123.4 ± 25.5 s), which was significantly greater (p = 0.001) than the CG (24.3 ± 18.5 s). By Week 48, the training-induced adaptations in the exercise groups returned to near baseline levels.

Conclusion: Our study supports current physical-activity recommendations that 150 min/week of moderate-intensity exercise produces improvements in fitness in previously sedentary older individuals. Also, LW and WW elicit similar improvements in fitness if conducted at the same relative intensities. Exercise-naïve older individuals can benefit from the lower impact forces and decreased risk of falls associated with WW without compromising improvements in cardiorespiratory fitness.
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http://dx.doi.org/10.1016/j.jshs.2019.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242220PMC
May 2020

Effects of Acute Exercise on Cutaneous Thermal Sensation.

Int J Environ Res Public Health 2020 04 6;17(7). Epub 2020 Apr 6.

Research Institute of Sports & Exercise Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.

The aim of this study was to assess the effect of exercise intensity on the thermal sensory function of active and inactive limbs. In a randomised and counterbalanced manner, 13 healthy young male participants (25 ± 6 years, 1.8 ± 0.1 m, 77 ± 6 kg) conducted: (1) 30-min low-intensity (50% heart rate maximum, HRmax; LOW) and (2) 30-min high-intensity (80% HRmax; HIGH) cycling exercises, and (3) 30 min of seated rest (CONTROL). Before, immediately after, and 1 h after, each intervention, thermal sensory functions of the non-dominant dorsal forearm and posterior calf were examined by increasing local skin temperature (1 °C/s) to assess perceptual heat sensitivity and pain thresholds. Relative to pre-exercise, forearm heat sensitivity thresholds were increased immediately and 1 hr after HIGH, but there were no changes after LOW exercise or during CONTROL (main effect of trial; = 0.017). Relative to pre-exercise, calf heat sensitivity thresholds were not changed after LOW or HIGH exercise or during CONTROL (main effect of trial; = 0.629). There were no changes in calf (main effect of trial; = 0.528) or forearm (main effect of trial; = 0.088) heat pain thresholds after exercise in either LOW or HIGH or CONTROL. These results suggest that cutaneous thermal sensitivity function of an inactive limb is only reduced after higher intensity exercise but is not changed in a previously active limb after exercise. Exercise does not affect heat pain sensitivity in either active or inactive limbs.
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http://dx.doi.org/10.3390/ijerph17072491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177974PMC
April 2020

The impact of acute remote ischaemic preconditioning on cerebrovascular function.

Eur J Appl Physiol 2020 Mar 13;120(3):603-612. Epub 2020 Jan 13.

Research Institute of Sport and Exercise Science, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool, L3 3AF, UK.

Purpose: Remote ischaemic preconditioning (RIPC) refers to the protection conferred to tissues and organs via brief periods of ischaemia in a remote vascular territory, including the brain. Recent studies in humans report that RIPC provides neuroprotection against recurrent (ischaemic) stroke. To better understand the ability of RIPC to improve brain health, the present study explored the potential for RIPC to acutely improve cerebrovascular function.

Methods: Eleven young healthy (females n = 6, age; 28.1 ± 3.7 years) and 9 older individuals (females n = 4, age 52.5 ± 6.7 years) at increased risk for stroke (cardiovascular disease risk factors) underwent assessments of cerebrovascular function, assessed by carbon dioxide (CO) reactivity and cerebral autoregulation during normo- and hypercapnia (5% CO) following 40 mins of bilateral arm RIPC or a sham condition. Squat-to-stand manoeuvres were performed to induce changes in blood pressure to assess cerebral autoregulation (0.10 Hz) and analysed via transfer function.

Results: We found no change in middle cerebral artery velocity or blood pressure across 40 mins of RIPC. Application of RIPC resulted in no change in CO reactivity slopes (sham vs RIPC, 1.97 ± 0.88 vs 2.06 ± 0.69 cm/s/mmHg P = 0.61) or parameters of cerebral autoregulation during normocapnia (sham vs RIPC, normalised gain%, 1.27 ± 0.25 vs 1.22 ± 0.35, P = 0.46).

Conclusion: This study demonstrates that a single bout of RIPC does not influence cerebrovascular function acutely in healthy individuals, or those at increased cardiovascular risk. Given the previously reported protective role of RIPC on stroke recurrence in humans, it is possible that repeated bouts of RIPC may be necessary to impart beneficial effects on cerebrovascular function.
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http://dx.doi.org/10.1007/s00421-019-04297-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042189PMC
March 2020

Visualizing and quantifying the impact of reactive hyperemia on cutaneous microvessels in humans.

J Appl Physiol (1985) 2020 01 14;128(1):17-24. Epub 2019 Nov 14.

Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia.

The mechanisms underlying reactive hyperemia (RH) responses in microvessels are poorly understood. Previous assessment tools have not been capable of directly visualizing microvessels during physiological stimulation in humans. Optical coherence tomography (OCT) is capable of imaging and quantifying subcutaneous microvessels as small as ~30 µm. In this study we use OCT to visualize and quantify skin microvascular changes in response to RH for the first time in humans. We also assessed the reproducibility of this technique. OCT and laser Doppler flowmetry (LDF) were used simultaneously to scan cutaneous microvessels in 10 young healthy subjects on 2 days. We applied a speckle decorrelation algorithm to assess OCT images and calculated flow rate, speed, diameter, and density parameters. Measures were obtained at rest (baseline) and 30-s following a 5-min cuff inflation (RH). All data were compared between days. The RH stimulus significantly increased ( < 0.0001) OCT-derived microvascular diameter (37.6 ± 3.4 vs. 44.5 ± 5.2 µm), flow rate (82.4 ± 23.4 vs. 240.1 ± 58.6 pl/s), speed (48 ± 5.7 vs. 101.5 ± 17.1 µm/s), density (5.1 ± 1.7 vs. 14.6 ± 2.6%), and also LDF-derived flux (12.3 ± 5.7 vs. 31.6 ± 9.1 perfusion units). At baseline, OCT-derived diameter ( = 0.55), flow rate (= 0.64), speed ( = 0.55), and density ( = 0.75) showed significant between-day correlations ( < 0.05), as did LDF results ( = 0.74). In response to RH, OCT-derived diameter ( = 0.63) and density ( = 0.64) showed significant correlations ( < 0.05), whereas flow rate ( = 0.45), speed ( = 0.43), and LDF ( = 0.26) were less reproducible. Our study is novel in that it establishes the feasibility of using OCT to visualize and quantify microvascular structure and function responses to RH in humans. This study describes the first evidence in humans that optical coherence tomography provides direct visualization and comprehensive quantification of cutaneous microvascular hemodynamics as a response to reactive hyperemia. This imaging technique will greatly improve human cutaneous microvascular assessment in physiological and clinical settings.
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http://dx.doi.org/10.1152/japplphysiol.00583.2019DOI Listing
January 2020

Seven-day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study.

Eur J Endocrinol 2019 Dec;181(6):659-669

Research Institute of Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK.

Background: Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC could improve endothelial and cerebrovascular function. The aim of this pilot study was to obtain estimates for the change in conduit artery and cerebrovascular function following a 7-day rIPC intervention.

Methods: Twenty-one patients with T2DM were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 220 mmHg, interspaced by 5-min reperfusion) or control. We examined peripheral endothelial function using flow mediated dilation (FMD) before and after ischemia-reperfusion injury (IRI, 20 min forearm ischaemic-20 min reperfusion) and cerebrovascular function, assessed by dynamic cerebral autoregulation (dCA) at three time points; pre, post and 8 days post intervention.

Results: For exploratory purposes, we performed statistical analysis on our primary comparison (pre-to-post) to provide an estimate of the change in the primary and secondary outcome variables. Using pre-intervention data as a covariate, the change from pre-post in FMD was 1.3% (95% CI: 0.69 to 3.80; P = 0.09) and 0.23 %cm/s %/mmHg mmHg/% (-0.12, 0.59; P = 0.18) in dCA normalised gain with rIPC versus control. Based upon this, a sample size of 20 and 50 for FMD and normalised gain, respectively, in each group would provide 90% power to detect statistically significant (P < 0.05) between-group difference in a randomised controlled trial.

Conclusion: We provide estimates of sample size for a randomised control trial exploring the impact of daily rIPC for 7 days on peripheral endothelial and cerebrovascular function. The directional changes outline from our pilot study suggest peripheral endothelial function can be enhanced by daily rIPC in patients with T2DM.
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http://dx.doi.org/10.1530/EJE-19-0378DOI Listing
December 2019

Lifelong Physical Activity Determines Vascular Function in Late Postmenopausal Women.

Med Sci Sports Exerc 2020 03;52(3):627-636

Department of Nutrition Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.

Introduction: The study evaluated the role of lifelong physical activity for leg vascular function in postmenopausal women (61 ± 1 yr).

Method: The study design was cross-sectional with three different groups based on self-reported physical activity level with regard to intensity and volume over the past decade: inactive (n = 14), moderately active (n = 12), and very active (n = 15). Endothelial-dependent and smooth muscle-dependent leg vascular function were assessed by ultrasound Doppler measurements of the femoral artery during infusion of acetylcholine (Ach), the nitric oxide (NO) donor sodium nitroprusside and the prostacyclin analog epoprostenol. Thigh muscle biopsies, arterial and venous plasma samples were obtained for assessment of vasodilator systems.

Results: The very active group was found to have 76% greater responsiveness to Ach compared with the sedentary group accompanied by 200% higher prostacyclin synthesis during Ach infusion. Smooth muscle cell responsiveness to sodium nitroprusside and epoprostenol was not different between groups. The protein amount of endothelial NO synthase and endogenous antioxidant enzymes in muscle tissue was higher in the very active than the inactive group. The moderately active group had a similar endothelial and smooth muscle cell responsiveness as the inactive group. A secondary comparison with a smaller group (n = 5) of habitually active young (24 ± 2 yr) women indicated that smooth muscle cell responsiveness and endothelial responsiveness are affected by age per se.

Conclusions: This study shows that leg vascular function and the potential to form prostacyclin and NO in late postmenopausal women, is influenced by the extent of lifelong physical activity.
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http://dx.doi.org/10.1249/MSS.0000000000002180DOI Listing
March 2020

Assessment of the human cutaneous microvasculature using optical coherence tomography: Proving Harvey's proof.

Microcirculation 2020 02 22;27(2):e12594. Epub 2019 Oct 22.

Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, WA, Australia.

William Harvey proved the circulation of blood 400 years ago using a combination of ligature application and astute observation that presaged the existence of capillaries. Here we report findings, based on our development of a novel application of optical coherence tomography (OCT), that directly confirm the impact of cuff inflation on microvessels as small as ~30µm. By emulating Harvey's proofs, using cuff inflation at low pressure in the presence and absence of skin heating, we have imaged and quantified significant effects on microvascular diameter and density in humans in vivo. The application of cuff pressure significantly increased microvascular diameter (40.5 ± 4.6 vs 47.1 ± 3.9 µm, P = .01) and density (8.33 ± 4.3 vs 15.1 ± 4.9%, P < .01). These impacts were reversed by cuff deflation. Our study also showed the profound impacts of skin heating on microvessel diameter (46.7 ± 5.8 vs 70.6 ± 7.8 µm, P < .01) and density (14.2 ± 6.5 vs 43.2 ± 9%, P < .01) in vivo, which were further exacerbated by cuff inflation. Our approach to the direct visualization of the human skin microvasculature is non-invasive, safe, and easily applied. Future experiments might be directed at questions of microvascular physiology and pathophysiology, such as how different mammals thermoregulate and what impacts cardiovascular disease and diabetes have on microvascular structure and function.
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http://dx.doi.org/10.1111/micc.12594DOI Listing
February 2020

Land- versus water-walking interventions in older adults: Effects on body composition.

J Sci Med Sport 2020 Feb 28;23(2):164-170. Epub 2019 Aug 28.

School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Australia. Electronic address:

Objectives: Increasing physical activity is a priority worldwide, including for older adults who may have difficulty performing traditional forms of exercise, and for whom retention of muscle mass is an important consideration. Water-based exercise may provide an alternative if benefits are comparable. We compared the impact on body composition of 24-week water- versus land-walking interventions in healthy but inactive older adults.

Design: Randomised, controlled trial.

Methods: 72 participants (62.5±6.8yr) were randomised to a land-walking (LW), water-walking (WW) or control (C) group in a supervised centre-based program. The exercise groups trained 3 times/week at matched intensity (%HRR), increasing from 40-45% to 55-65% heart rate reserve (HRR). Height, weight, body mass index (BMI), waist and hip girths were recorded; dual X-ray absorptiometry (DXA) provided fat and lean tissue masses. Participants were re-assessed 24 weeks after completion of the intervention.

Results: There were no significant changes in body mass or BMI following either exercise protocol, however central adiposity was reduced in both exercise groups, and the WW group increased lower limb lean mass. These benefits did not persist over the follow-up period.

Conclusions: Exercise can confer beneficial effects on body composition which are not evident when examining weight or BMI. Both WW and LW improved body composition. Water walking can be recommended as an exercise strategy for this age group due to its beneficial effects on body composition which are similar to, or exceed, those associated with land-walking. For benefits to persist, it appears that exercise needs to be maintained.
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http://dx.doi.org/10.1016/j.jsams.2019.08.019DOI Listing
February 2020

UBC-Nepal Expedition: Haemoconcentration underlies the reductions in cerebral blood flow observed during acclimatization to high altitude.

Exp Physiol 2019 12 28;104(12):1963-1972. Epub 2019 Aug 28.

Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia - Okanagan Campus, Kelowna, BC, Canada.

New Findings: What is the central question of this study? The aim was to evaluate the degree to which increases in haematocrit alter cerebral blood flow and cerebral oxygen delivery during acclimatization to high altitude. What is the main finding and its importance? Through haemodilution, we determined that, after 1 week of acclimatization, the primary mechanism contributing to the cerebral blood flow response during acclimatization is an increase in haemoglobin and haematocrit. The remaining contribution to the cerebral blood flow response during acclimatization is likely to be attributable to ventilatory acclimatization.

Abstract: At high altitude, an increase in haematocrit (Hct) is achieved through altitude-induced diuresis and erythropoiesis, both of which result in increased arterial oxygen content. Given the impact of alterations in Hct on oxygen content, haemoconcentration has been hypothesized to mediate, in part, the attenuation of the initial elevation in cerebral blood flow (CBF) at high altitude. To test this hypothesis, healthy men (n = 13) ascended to 5050 m over 9 days without the aid of prophylactic acclimatization medications. After 1 week of acclimatization at 5050 m, participants were haemodiluted by rapid saline infusion (2.10 ± 0.28 l) to return Hct towards pre-acclimatization values. Arterial blood gases, Hct, global CBF (duplex ultrasound) and haemodynamic variables were measured after initial arrival at 5050 m and after 1 week of acclimatization at high altitude, before and after the haemodilution protocol. After 1 week at 5050 m, the Hct increased from 42.5 ± 2.5 to 49.6 ± 2.5% (P < 0.001), and it was subsequently reduced to 45.6 ± 2.3% (P < 0.001) after haemodilution. Global CBF decreased from 844 ± 160 to 619 ± 136 ml min (P = 0.033) after 1 week of acclimatization and increased to 714 ± 204 ml min (P = 0.045) after haemodilution. Despite the significant changes in Hct, and thus oxygen content, cerebral oxygen delivery was unchanged at all time points. Furthermore, these observations occurred in the absence of any changes in mean arterial blood pressure, cardiac output, arterial blood pH or oxygen saturation pre- and posthaemodilution. These data highlight the influence of Hct in the regulation of CBF and are the first to demonstrate experimentally that haemoconcentration contributes to the reduction in CBF during acclimatization to altitude.
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http://dx.doi.org/10.1113/EP087663DOI Listing
December 2019

UBC-Nepal expedition: phenotypical evidence for evolutionary adaptation in the control of cerebral blood flow and oxygen delivery at high altitude.

J Physiol 2019 06 13;597(12):2993-3008. Epub 2019 May 13.

Centre for Heart, Lung and Vascular Health, University of British Columbia-Okanagan Campus, School of Health and Exercise Sciences, 3333 University Way, Kelowna, British Columbia, Canada, V1V 1V7.

Key Points: Sherpa have lived in the Nepal Himalaya for 25-40 thousand years and display positive physiological adaptations to hypoxia. Sherpa have previously been demonstrated to suffer less negative cerebral side effects of ascent to extreme altitude, yet little is known as to whether or not they display differential regulation of oxygen delivery to the brain compared to lowland natives. We demonstrate that Sherpa have lower brain blood flow during ascent to and acclimatization at high altitude compared to lowlanders and that this difference in flow is not attributable to factors such as mean arterial pressure, blood viscosity and pH. The observed lower cerebral oxygen delivery in Sherpa likely represents a positive adaptation that may indicate a cerebral hypometabolic conservation of energy at altitude and/or decreased risk of other cerebral consequences such as vasogenic oedema.

Abstract: Debilitating side effects of hypoxia manifest within the central nervous system; however, high-altitude natives of the Tibetan plateau, the Sherpa, experience negligible cerebral effects compared to lowland natives at extreme altitude. Phenotypical optimization of the oxygen cascade has been demonstrated in the systemic circulation of Tibetans and Sherpa, likely underscoring their adapted capacity to thrive at altitude. Yet, little is known as to how the cerebral circulation of Sherpa may be adapted. To examine potential differences in cerebral oxygen delivery in Sherpa compared to lowlanders we measured arterial blood gases and global cerebral blood flow (duplex ultrasound) during a 9 day ascent to 5050 m. Although cerebral oxygen delivery was maintained during ascent in lowlanders, it was significantly reduced in the Sherpa at 3400 m (-30.3 ± 21.6%; P < 0.01) and 4371 m (-14.2 ± 10.7%; P = 0.03). Furthermore, linear mixed effects modelling indicated that independent of differences in mean arterial pressure, pH and blood viscosity, race accounts for an approximately 100 mL min (∼17-34%) lower cerebral blood flow in Sherpa compared to lowlanders across ascent to altitude (P = 0.046). To ascertain the role of chronic hypoxia independent of the ascent, Sherpa who had not recently descended were also examined at 5050 m. In these Sherpa, cerebral oxygen delivery was also lower compared to lowlanders (∼22% lower; P < 0.01). We highlight new information about the influence of race and genetic adaptation in the regulation of cerebral oxygen delivery. The lower cerebral oxygen delivery in the Sherpa potentially represents a positive adaptation considering Sherpa endure less deleterious cerebral consequences than lowlanders at altitude.
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http://dx.doi.org/10.1113/JP277596DOI Listing
June 2019

Novel Noninvasive Assessment of Microvascular Structure and Function in Humans.

Med Sci Sports Exerc 2019 07;51(7):1558-1565

Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), Faculty of Science, The University of Western Australia, Perth, AUSTRALIA.

Introduction: Optical coherence tomography (OCT) is a novel high-resolution imaging technique capable of visualizing in vivo structures at a resolution of ~10 μm. We have developed specialized OCT-based approaches that quantify diameter, speed, and flow rate in human cutaneous microvessels. In this study, we hypothesized that OCT-based microvascular assessments would possess comparable levels of reliability when compared with those derived using conventional laser Doppler flowmetry (LDF).

Methods: Speckle decorrelation images (OCT) and red blood cell flux (LDF) measures were collected from adjacent forearm skin locations on 2 d (48 h apart), at baseline, and after a 30-min rapid local heating protocol (30°C-44°C) in eight healthy young individuals. OCT postprocessing quantified cutaneous microvascular diameter, speed, flow rate, and density (vessel recruitment) within a region of interest, and data were compared between days.

Results: Forearm skin LDF (13 ± 4 to 182 ± 31 AU, P < 0.05) and OCT-derived diameter (41.8 ± 6.6 vs 64.5 ± 6.9 μm), speed (68.4 ± 9.5 vs 89.0 ± 7.3 μm·s), flow rate (145.0 ± 60.6 vs 485 ± 132 pL·s), and density (9.9% ± 4.9% vs 45.4% ± 5.9%) increased in response to local heating. The average OCT-derived microvascular flow response (pL·s) to heating (234% increase) was lower (P < 0.05) than the LDF-derived change (AU) (1360% increase). Pearson correlation was significant for between-day local heating responses in terms of OCT flow (r = 0.93, P < 0.01), but not LDF (P = 0.49). Bland-Altman analysis revealed that between-day baseline OCT-derived flow rates were less variable than LDF-derived flux.

Conclusions: Our findings indicate that OCT, which directly visualizes human microvessels, not only allows microvascular quantification of diameter, speed, flow rate, and vessel recruitment but also provides outputs that are highly reproducible. OCT is a promising novel approach that enables a comprehensive assessment of cutaneous microvascular structure and function in humans.
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http://dx.doi.org/10.1249/MSS.0000000000001898DOI Listing
July 2019

UBC-Nepal expedition: upper and lower limb conduit artery shear stress and flow-mediated dilation on ascent to 5,050 m in lowlanders and Sherpa.

Am J Physiol Heart Circ Physiol 2018 12 31;315(6):H1532-H1543. Epub 2018 Aug 31.

Centre for Heart, Lung, and Vascular Health, University of British Columbia-Okanagan, Kelowna, British Columbia, Canada.

The study of conduit artery endothelial adaptation to hypoxia has been restricted to the brachial artery, and comparisons with highlanders have been confounded by differences in altitude exposure, exercise, and unknown levels of blood viscosity. To address these gaps, we tested the hypothesis that lowlanders, but not Sherpa, would demonstrate decreased mean shear stress and increased retrograde shear stress and subsequently reduced flow-mediated dilation (FMD) in the upper and lower limb conduit arteries on ascent to 5,050 m. Healthy lowlanders (means ± SD, n = 22, 28 ± 6 yr) and Sherpa ( n = 12, 34 ± 11 yr) ascended over 10 days, with measurements taken on nontrekking days at 1,400 m (baseline), 3,440 m ( day 4), 4,371 m ( day 7), and 5,050 m ( day 10). Arterial blood gases, blood viscosity, shear stress, and FMD [duplex ultrasound of the brachial and superficial femoral arteries (BA and SFA, respectively)] were acquired at each time point. Ascent decreased mean and increased retrograde shear stress in the upper and lower limb of lowlanders and Sherpa. Although BA FMD decreased in lowlanders from 7.1 ± 3.9% to 3.8 ± 2.8% at 5,050 versus 1,400 m ( P < 0.001), SFA FMD was preserved. In Sherpa, neither BA nor SFA FMD were changed upon ascent to 5,050 m. In lowlanders, the ascent-related exercise may favorably influence endothelial function in the active limb (SFA); selective impairment in FMD in the BA in lowlanders is likely mediated via the low mean or high oscillatory baseline shear stress. In contrast, Sherpa presented protected endothelial function, suggesting a potential vascular aspect of high-altitude acclimatization/adaptation. NEW & NOTEWORTHY Upper and lower limb arterial shear stress and flow-mediated dilation (FMD) were assessed on matched ascent from 1,400 to 5,050 m in lowlanders and Sherpa. A shear stress pattern associated with vascular dysfunction/risk manifested in both limbs of lowlanders and Sherpa. FMD was impaired only in the upper limb of lowlanders. The findings indicate a limb-specific impact of high-altitude trekking on FMD and a vascular basis to acclimatization wherein endothelial function is protected in Sherpa on ascent.
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http://dx.doi.org/10.1152/ajpheart.00345.2018DOI Listing
December 2018

HSP90: an unappreciated mediator of cutaneous vascular adaptation?

J Appl Physiol (1985) 2018 02;124(2):521

School of Sport Science, Exercise and Health, The University of Western Australia, Australia.

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http://dx.doi.org/10.1152/japplphysiol.00992.2017DOI Listing
February 2018

UBC-Nepal expedition: The use of oral antioxidants does not alter cerebrovascular function at sea level or high altitude.

Exp Physiol 2018 04 8;103(4):523-534. Epub 2018 Mar 8.

Centre for Heart, Lung & Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Okanagan Campus, Kelowna, BC, Canada.

New Findings: What is the central question of the study? Does the use of antioxidants alter cerebrovascular function and blood flow at sea level (344 m) and/or high altitude (5050 m)? What is the main finding and its importance? This is the first study to investigate whether antioxidant administration alters cerebrovascular regulation and blood flow in response to hypercapnia, acute hypoxia and chronic hypoxia in healthy humans. We demonstrate that an acute dose of antioxidants does not alter cerebrovascular function and blood flow at sea level (344 m) or after 12 days at high altitude (5050 m).

Abstract: Hypoxia is associated with an increase in systemic and cerebral formation of free radicals and associated reactants that may be linked to impaired cerebral vascular function and neurological sequelae. To what extent oral antioxidant prophylaxis impacts cerebrovascular function in humans throughout the course of acclimatization to the hypoxia of terrestrial high altitude has not been examined. Thus, the purpose of the present study was to examine the influence of orally ingested antioxidants at clinically relevant doses (vitamins C and E and α-lipoic acid) on cerebrovascular regulation at sea level (344 m; n = 12; female n = 2 participants) and at high altitude (5050 m; n = 9; female n = 2) in a randomized, placebo-controlled and double-blinded crossover design. Hypercapnic and hypoxic cerebrovascular reactivity tests of the internal carotid artery (ICA) were conducted at sea level, and global and regional cerebral blood flow (CBF; i.e. ICA and vertebral artery) were assessed 10-12 days after arrival at 5050 m. At sea level, acute administration of antioxidants did not alter cerebral hypoxic cerebrovascular reactivity (pre versus post: 1.5 ± 0.7 versus 1.2 ± 0.8%∆CBF/-%∆SpO2; P = 0.96) or cerebral hypercapnic cerebrovascular reactivity (pre versus post: 5.7 ± 2.0 versus 5.8 ± 1.9%∆CBF/∆mmHg; P = 0.33). Furthermore, global CBF (P = 0.43) and cerebral vascular conductance (ICA P = 0.08; vertebral artery P = 0.32) were unaltered at 5050 m after antioxidant administration. In conclusion, these data show that an oral antioxidant cocktail known to attenuate systemic oxidative stress failed to alter cerebrovascular function at sea level and CBF during acclimatization to high altitude.
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http://dx.doi.org/10.1113/EP086887DOI Listing
April 2018

Localised cutaneous microvascular adaptation to exercise training in humans.

Eur J Appl Physiol 2018 Apr 7;118(4):837-845. Epub 2018 Feb 7.

School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Crawley, WA, 6009, Australia.

Purpose: Exercise training induces adaptation in conduit and resistance arteries in humans, partly as a consequence of repeated elevation in blood flow and shear stress. The stimuli associated with intrinsic cutaneous microvascular adaptation to exercise training have been less comprehensively studied.

Methods: We studied 14 subjects who completed 8-weeks cycle ergometer training, with partial cuff inflation on one forearm to unilaterally attenuate cutaneous blood flow responses during each exercise-training bout. Before and after training, bilateral forearm skin microvascular dilation was determined using cutaneous vascular conductance (CVC: skin flux/blood pressure) responses to gradual localised heater disk stimulation performed at rest (33, 40, 42 and 44 °C).

Results: Cycle exercise induced significant increases in forearm cutaneous flux and temperature, which were attenuated in the cuffed arm (2-way ANOVA interaction-effect; P < 0.01). We found that forearm CVC at 42 and 44 °C was significantly lower in the uncuffed arm following 8-weeks of cycle training (P < 0.01), whereas no changes were apparent in the contralateral cuffed arm (P = 0.77, interaction-effect P = 0.01).

Conclusions: Lower limb exercise training in healthy young men leads to lower CVC-responses to a local heating stimulus, an adaptation mediated, at least partly, by a mechanism related to episodic increases in skin blood flow and/or skin temperature.
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http://dx.doi.org/10.1007/s00421-018-3813-3DOI Listing
April 2018

Sympatholysis: the more we learn, the less we know.

J Physiol 2018 03 12;596(6):963-964. Epub 2018 Feb 12.

Department of Nutrition, Exercise and Sports, Section for Integrative Physiology, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1113/JP275513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851886PMC
March 2018

Brachial and Cerebrovascular Functions Are Enhanced in Postmenopausal Women after Ingestion of Chocolate with a High Concentration of Cocoa.

J Nutr 2017 09 9;147(9):1686-1692. Epub 2017 Aug 9.

School of Sport Science, Exercise and Health, University of Western Australia, Crawley, Western Australia, Australia;

Cocoa contains polyphenols that are thought to be beneficial for vascular health. We assessed the impact of chocolate containing distinct concentrations of cocoa on cerebrovascular function and cognition. Using a counterbalanced within-subject design, we compared the acute impact of consumption of energy-matched chocolate containing 80%, 35%, and 0% single-origin cacao on vascular endothelial function, cognition, and cerebrovascular function in 12 healthy postmenopausal women (mean ± SD age: 57.3 ± 5.3 y). Participants attended a familiarization session, followed by 3 experimental trials, each separated by 1 wk. Outcome measures included cerebral blood flow velocity (CBF) responses, recorded before and during completion of a computerized cognitive assessment battery (CogState); brachial artery flow-mediated dilation (FMD); and hemodynamic responses (heart rate and blood pressure). When CBF data before and after chocolate intake were compared between conditions through the use of 2-factor ANOVA, an interaction effect ( = 0.003) and main effects for chocolate ( = 0.043) and time ( = 0.001) were evident. Post hoc analysis revealed that both milk chocolate (MC; 35% cocoa; = 0.02) and dark chocolate (DC; 80% cocoa; = 0.003) induced significantly lower cerebral blood flow responses during the cognitive tasks, after normalizing for changes in arterial pressure. DC consumption also increased brachial FMD compared with the baseline value before chocolate consumption ( = 0.002), whereas MC and white chocolate (0% cocoa) caused no change (interaction between conditions = 0.034). Consumption of chocolate containing high concentrations of cocoa enhanced vascular endothelial function, which was reflected by improvements in FMD. Cognitive function outcomes did not differ between conditions; however, cerebral blood flow responses during these cognitive tasks were lower in those consuming MC and DC. These findings suggest that chocolate containing high concentrations of cocoa may modify the relation between cerebral metabolism and blood flow responses in postmenopausal women. This trial was registered at www.ANZCTR.orgau as ACTRN12616000990426.
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http://dx.doi.org/10.3945/jn.117.250225DOI Listing
September 2017

Differential impact of water immersion on arterial blood flow and shear stress in the carotid and brachial arteries of humans.

Physiol Rep 2017 May;5(10):e13285

School of Human Sciences, The University of Western Australia, Crawley, Western Australia.

Arterial shear stress is a potent stimulus to vascular adaptation in humans. Typically, increases in retrograde shear have been found to acutely impair vascular function while increases in antegrade shear enhance function. We hypothesized that blood flow and shear stress through the brachial and carotid arteries would change in a similar manner in response to water immersion, an intervention which modifies hemodynamics. Nine healthy young male subjects were recruited to undergo controlled water immersion in a standing upright position to the level of the right atrium in 30°C water. Diameters were continuously and simultaneously recorded in the brachial and common carotid arteries along with mean arterial pressure (MAP), cardiac output (CO), and heart rate before, during, and after 10 min of immersion. MAP and CO increased during water immersion (baseline vs. 8-10 min; 80 ± 9 vs. 91 ± 12 mmHg; and 4.8 ± 0.7 vs. 5.1 ± 0.6 L/min,  < 0.01 and  < 0.05, respectively). We observed a differential regulation of flow and shear stress patterns in the brachial and carotid arteries in response to water immersion; brachial conductance decreased markedly in response to immersion (1.25 ± 0.56 vs. 0.57 ± 0.30 mL.min/mmHg,  < 0.05), whereas it was unaltered in the carotid artery (5.82 ± 2.14 vs. 5.60 ± 1.59). Our findings indicate that adaptations to systemic stimuli and arterial adaptation may be vessel bed specific in humans, highlighting the need to assess multiple vascular sites in future studies.
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http://dx.doi.org/10.14814/phy2.13285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449564PMC
May 2017

Shear-mediated dilation of the internal carotid artery occurs independent of hypercapnia.

Am J Physiol Heart Circ Physiol 2017 Jul 7;313(1):H24-H31. Epub 2017 Apr 7.

Centre for Heart, Lung, and Vascular Health, University of British Columbia Okanagan Campus, School of Health and Exercise Sciences, Kelowna, British Columbia, Canada.

Evidence for shear stress as a regulator of carotid artery dilation in response to increased arterial CO was recently demonstrated in humans during sustained elevations in CO (hypercapnia); however, the relative contributions of CO and shear stress to this response remains unclear. We examined the hypothesis that, after a 30-s transient increase in arterial CO tension and consequent increase in internal carotid artery shear stress, internal carotid artery diameter would increase, indicating shear-mediated dilation, in the absence of concurrent hypercapnia. In 27 healthy participants, partial pressures of end-tidal O and CO, ventilation (pneumotachography), blood pressure (finger photoplethysmography), heart rate (electrocardiogram), internal carotid artery flow, diameter, and shear stress (high-resolution duplex ultrasound), and middle cerebral artery blood velocity (transcranial Doppler) were measured during 4-min steady-state and transient 30-s hypercapnic tests (both +9 mmHg CO). Internal carotid artery dilation was lower in the transient compared with steady-state hypercapnia (3.3 ± 1.9 vs. 5.3 ± 2.9%, respectively, < 0.03). Increases in internal carotid artery shear stress preceded increases in diameter in both transient (time: 16.8 ± 13.2 vs. 59.4 ± 60.3 s, < 0.01) and steady-state (time: 18.2 ± 14.2 vs. 110.3 ± 79.6 s, < 0.01) tests. Internal carotid artery dilation was positively correlated with shear rate area under the curve in the transient ( = 0.44, < 0.01) but not steady-state ( = 0.02, = 0.53) trial. Collectively, these results suggest that hypercapnia induces shear-mediated dilation of the internal carotid artery in humans. This study further promotes the application and development of hypercapnia as a clinical strategy for the assessment of cerebrovascular vasodilatory function and health in humans. Shear stress dilates the internal carotid artery in humans. This vasodilatory response occurs independent of other physiological factors, as demonstrated by our transient CO test, and is strongly correlated to shear area under the curve. Assessing carotid shear-mediated dilation may provide a future avenue for assessing cerebrovascular health and the risk of cerebrovascular events.
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http://dx.doi.org/10.1152/ajpheart.00119.2017DOI Listing
July 2017

Reproducibility of four frequently used local heating protocols to assess cutaneous microvascular function.

Microvasc Res 2017 07 22;112:65-71. Epub 2017 Mar 22.

Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK. Electronic address:

Background: Skin microvascular responses to local heating are frequently used to assess microvascular function. Several local heating protocols have been developed, all varying slightly in execution. The aim of this study was to determine the inter-day reproducibility of the four most commonly used local heating protocols in healthy young subjects.

Methods: Fifteen, healthy males (28±5yrs, BMI 25±2kg/m) attended two experimental trials 2-7days apart. During each trial, baseline and maximal thermally stimulated forearm skin responses were examined simultaneously at four sites on the dominant forearm using laser Doppler flowmetry (LDF). The following heating protocols were adopted: 1. Rapid 39°C (0.5°C/5s), 2. Rapid 42°C (0.5°C/5s) 3. Gradual 42°C (0.5°C/2min 30s) and 4. Slow 42°C (0.5°C/5min). The coefficient of variation (CV) was calculated for absolute flux, cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC at 44°C (%CVC) at three different time points; baseline (33°C), plateau (39/42°C) and maximal (44°C).

Results: Reproducibility of baseline flux, CVC and %CVC was 17-29% across all protocols. During the plateau, Rapid, Gradual and Slow 42°C demonstrated a reproducibility of 13-18% for flux and CVC and 5-11% for %CVC. However, Rapid 39°C demonstrated a lower reproducibility for flux, CVC and %CVC (all 21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols.

Conclusion: This is the first study examining inter-day reproducibility across four local heating protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols support their (simultaneous) use to assess microvascular function. Using Rapid 39°C may require a greater number of subjects to detect differences within subjects.
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http://dx.doi.org/10.1016/j.mvr.2017.03.005DOI Listing
July 2017