The impact of exercise and thermal training interventions on thermoregulatory and cardiovascular function in young and post-menopausal females

The female reproductive hormone oestrogen influences cardiovascular and thermoregulatory control. A dramatic decline in oestrogen during the menopause causes cardiovascular and thermoregulatory dysfunction resulting in hot flushes (HFs). HFs consist of feelings of intense heat with rapid increases in cutaneous vasodilation and sweating that severely affect quality of life and increase cardiovascular disease risk. Treatment using hormone replacement therapy for HFs is contraindicated in some symptomatic females meaning an alternative strategy is warranted. Exercise training may reduce HFs; however no study to date has examined the physiological mechanisms that cause changes in the frequency and severity of HFs following a period of exercise training. Exercise training is known to enhance thermoregulatory efficiency via an earlier core temperature onset for cutaneous vasodilation and sweating in pre-menopausal females. Exercise training is also known to positively impact vascular function in the conduit, cutaneous and cerebral vessels and thus can also decrease cardiovascular risk in symptomatic post-menopausal females. Heat acclimation interventions target the same thermoregulatory and cardiovascular physiological mechanisms, and may also be beneficial. The primary aim of this thesis was to (i) examine whether exercise training reduces objectively measured HFs via improving cardiovascular and thermoregulatory dysfunction in symptomatic post-menopausal females, and to (ii) assess the efficacy of an exercise-independent stimulus in improving thermoregulatory and cardiovascular function in pre-menopausal females.Twenty-one symptomatic post-menopausal females completed a 16-week exercise training intervention (n=14, 52±4y, 29±6 kg/m2) or a no-exercise control intervention (n=7, 52±6y, 30±7 kg/m2). Cardiorespiratory fitness (VO2peak) and brachial artery endothelial function was assessed using flow-mediated dilation (FMD). Participants underwent a passive heat stress in a water-perfused suit (~48ºC) to obtain core temperature thresholds and sensitivities for cutaneous vascular conductance (CVC) and sweat rate at two sites (chest and forearm). Middle cerebral artery velocity (MCAv) was measured at rest and throughout the heat stress. All measurements were repeated following the intervention period. HFs reduced by 39 HF•wk (95% CI= 31, 47) following exercise training compared to no change in control. HF-severity reduced by 101 (AU) (95% CI= 80, 121) following exercise training compared to no change in control. VO2peak and FMD improved (P0.05). This was accompanied by a reduction in chest skin blood flow of 26 AU (95% CI, 21, 30; P=0.01) during HFs following exercise training compared to no change in control (P=0.10). MCAv was attenuated by 3.4 cm/s (95% CI, 0.7, 5.1; P<0.001) during a HF following exercise training compared to control [0.6 cm/s (95% CI, -0.7, 1.8; P=0.93)].Eighteen pre-menopausal females (25±8y) were assigned to 3x30-min of cycling exercise (70% HRmax) or warm water immersion (42ºC) to the level of the sternum for 8-weeks. FMD (P=0.003) and VO2peak (P<0.001) improved following both interventions. Core body temperature reduced by 0.14ºC (95% CI, 0.04, 0.23; P=0.004) following both interventions. Sweat rate mean body temperature thresholds at the chest and forearm occurred 0.10ºC (95% CI=-0.14, 0.33, P<0.001) and 0.19ºC (0.12, 0.23ºC, P<0.001) earlier following the interventions, alongside an increase in sweat rate sensitivity of 1.18 mg•cm2•min-1 (95% CI= 0.68, 1.67; P<0.001) following water immersion compared to 0.28 mg•cm2•min-1 (95% CI= 0.23, 0.78) following exercise training. CVC core temperature thresholds occurred ~0.20ºC earlier at the chest and forearm (P<0.001). Resting MCAv was 2.30 cm/s (95% CI=1.20, 3.34; P<0.001) higher, with decreases in MCAv attenuated during heat stress, following both interventions.The findings from this thesis suggest that reductions in the frequency and severity of HFs with exercise training are mediated by improvements in thermoregulatory function, alongside cerebral, conduit and cutaneous adaptation. This coincided with objective reductions in HF severity following exercise training, with attenuation in the physiological perturbations observed during an acute HF. Consequently, interventions that target thermoregulatory function may be useful in reducing post-menopausal HFs. In keeping with the exercise mediated physiological changes, warm water immersion training also elicits similar favourable thermoregulatory, conduit- and cerebrovascular adaptations to a period of moderate intensity exercise training in pre-menopausal females. Immersion therapy may therefore be applicable to HF-symptomatic post-menopausal females

Thermoregulatory responses to combined moderate heat stress and hypoxia

Objective: The aim of this study was to examine the cutaneous vascular and sudomotor responses to combined moderate passive heat stress and normobaric hypoxia. Method: Thirteen healthy young males, dressed in a water-perfused suit, underwent passive heating (Δcore temperature ~0.7 °C) twice (NORMOXIA; 20.9% O2 and HYPOXIA; 13% O2). Chest and forearm skin blood flow (SkBF; laser Doppler flux), local sweat rate (SR; capacitance hygrometry) and core (intestinal pill) and skin temperatures, were recorded. Results: HYPOXIA reduced baseline oxygen saturation (98±1 vs. 89±6%, P<0.001) and elevated chest (P=0.03) and forearm SkBF (P=0.03) and HR (64±9 vs. 69±8 beats.min-1, P<0.01). During heating, mean body temperature (T ̅BODY) thresholds for SkBF (P=0.41) and SR (P=0.28) elevations were not different between trials. The SkBF: T ̅BODY linear sensitivity during the initial phase of heating was lower at the Chest (P=0.035) but not different at the forearm (P=0.17) during HYPOXIA. With increasing levels of heating chest SkBF was not different (P=0.55) but forearm SkBF was lower on the forearm (P<0.01) during HYPOXIA. Chest (P=0.85) and forearm (P=0.79) SR:T ̅BODY linear sensitivities were not different between trials. Conclusion: Whilst sudomotor responses and the initiation of cutaneous blood flow elevations are unaffected, hypoxia differentially effects regional SkBF responses during moderate passive heating

Cardiorespiratory Fitness Modulates The Acute Flow-Mediated Dilation Response Following High-Intensity But Not Moderate-Intensity Exercise In Elderly Men.

Impaired endothelial function is observed with ageing and with low cardiorespiratory fitness (VO2peak) whilst improvements in both are suggested to be reliant on higher-intensity exercise in the elderly. This may be due to the flow-mediated dilation (FMD) response to acute exercise of varying intensity. We examined the hypothesis that exercise-intensity alters the FMD response in healthy elderly adults, and would be modulated by VO2peak Forty-seven elderly men were stratified into lower- (VO2peak = 24.3±2.9 ml.kg(-1)min(-1), n=27) and higher-fit groups (VO2peak = 35.4±5.5 ml.kg(-1)min(-1), n=20) after a test of cycling peak power output (PPO). In randomised order, participants undertook 27 min moderate-intensity continuous (MICE; 40% PPO) or high-intensity interval cycling exercise (HIIE; 70% PPO), or no-exercise control. Brachial FMD was assessed at rest, 10 and 60 min after exercise. In control, FMD reduced in both groups (P=0.05). FMD increased after MICE in both groups [increase of 0.86 % (95% CI, 0.17 to 1.56), P=0.01], and normalised after 60 min. In the lower-fit, FMD reduced after HIIE [reduction of 0.85 % (95% CI, 0.12 to 1.58), P=0.02), and remained decreased at 60 min (P=0.05). In the higher-fit FMD was unchanged immediately after HIIE and increased after 60 min [increase of 1.52 % (95% CI, 0.41 to 2.62), P<0.01], which was correlated with VO2peak (r =0.41; P<0.01). Exercise-intensity alters the FMD response in elderly adults, and VO2peak modulates the FMD response following HIIE, but not MICE. The sustained decrease in FMD in the lower-fit may represent a signal for vascular adaptation or endothelial fatigue

Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Background Ischaemic preconditioning has well-established cardiac and vascular protective effects. Short interventions (one week) of daily ischaemic preconditioning episodes improve conduit and microcirculatory function. This study examined whether a longer (eight weeks) and less frequent (three per week) protocol of repeated ischaemic preconditioning improves vascular function. Methods Eighteen males were randomly allocated to either ischaemic preconditioning (22.4 ± 2.3 years, 23.7 ± 3.1 kg/m2) or a control intervention (26.0 ± 4.8 years, 26.4 ± 1.9 kg/m2). Brachial artery endothelial-dependent (FMD), forearm cutaneous microvascular function and cardiorespiratory fitness were assessed at zero, two and eight weeks. Results A greater improvement in FMD was evident following ischaemic preconditioning training compared with control at weeks 2 (2.24% (0.40, 4.08); p=0.02) and 8 (1.11% (0.13, 2.10); p=0.03). Repeated ischaemic preconditioning did not change cutaneous microcirculatory function or fitness. Conclusions These data indicate that a feasible and practical protocol of regular ischaemic preconditioning episodes improves endothelial function in healthy individuals within two weeks, and these effects persist following repeated ischaemic preconditioning for eight weeks

Physical activity and menopausal symptoms in women who have received menopause-inducing cancer treatments: results from the Women's Wellness After Cancer Program.

ObjectiveThis randomized controlled trial tested a digitally-delivered whole-of-lifestyle program for women previously treated for cancer. We investigated (1) associations between self-reported physical activity (PA) and menopausal symptoms and (2) if the intervention was associated with beneficial changes in PA and menopausal symptoms.MethodsWomen were randomized to intervention (n = 142) or control (n = 138). The intervention targeted lifestyle behavior including PA. Self-reported PA (International Physical Activity Questionnaire - Short Form) and menopausal symptom (Green Climacteric Scale, GCS) data were collected at baseline, with measures repeated at 12 weeks (end of intervention) and 24 weeks (to assess sustainability). Generalized estimating equation models explored associations between PA and GCS scores. Mixed-effects generalized equation models analyzed changes within and between groups in PA and GCS scores.ResultsTotal GCS scores were 1.83 (95% CI: 0.11-3.55) and 2.72 (95% CI: 1.12-4.33) points lower in women with medium and high levels of PA, respectively, than in women with low levels of PA. Total average GCS scores were 1.02 (0.21-2.26) and 1.61 (0.34-2.87) points lower in those undertaking moderate or vigorous intensity PA, respectively. Time spent walking, and performing moderate and vigorous PA were not different between intervention and control. The average GCS decrease of 0.66 points (95% CI: 0.03-1.29; p time = 0.03) over 24 weeks was not different between groups.ConclusionThis exploratory study established a stepwise association between moderate and vigorous PA and a lower total menopausal symptom score. The intervention did not appear to increase self-reported PA in women treated for early stage breast, reproductive, and blood cancers

Foot kinematics in patients with two patterns of pathological plantar hyperkeratosis

Background: The Root paradigm of foot function continues to underpin the majority of clinical foot biomechanics practice and foot orthotic therapy. There are great number of assumptions in this popular paradigm, most of which have not been thoroughly tested. One component supposes that patterns of plantar pressure and associated hyperkeratosis lesions should be associated with distinct rearfoot, mid foot, first metatarsal and hallux kinematic patterns. Our aim was to investigate the extent to which this was true. Methods: Twenty-seven subjects with planter pathological hyperkeratosis were recruited into one of two groups. Group 1 displayed pathological plantar hyperkeratosis only under metatarsal heads 2, 3 and 4 (n = 14). Group 2 displayed pathological plantar hyperkeratosis only under the 1st and 5th metatarsal heads (n = 13). Foot kinematics were measured using reflective markers on the leg, heel, midfoot, first metatarsal and hallux. Results: The kinematic data failed to identify distinct differences between these two groups of subjects, however there were several subtle (generally <3°) differences in kinematic data between these groups. Group 1 displayed a less everted heel, a less abducted heel and a more plantarflexed heel compared to group 2, which is contrary to the Root paradigm. Conclusions: There was some evidence of small differences between planter pathological hyperkeratosis groups. Nevertheless, there was too much similarity between the kinematic data displayed in each group to classify them as distinct foot types as the current clinical paradigm proposes

Acute Dietary Nitrate Supplementation Improves Flow Mediated Dilatation of the Superficial Femoral Artery in Healthy Older Males

Aging is often associated with reduced leg blood flow, increased arterial stiffness, and endothelial dysfunction, all of which are related to declining nitric oxide (NO) bioavailability. Flow mediated dilatation (FMD) and passive leg movement (PLM) hyperaemia are two techniques used to measure NO-dependent vascular function. We hypothesised that acute dietary nitrate (NO3−) supplementation would improve NO bioavailability, leg FMD, and PLM hyperaemia. Fifteen healthy older men (69 ± 4 years) attended two experiment sessions and consumed either 140 mL of concentrated beetroot juice (800 mg NO3−) or placebo (NO3−-depleted beetroot juice) in a randomised, double blind, cross-over design study. Plasma nitrite (NO2−) and NO3−, blood pressure (BP), augmentation index (AIx75), pulse wave velocity (PWV), FMD of the superficial femoral artery, and PLM hyperaemia were measured immediately before and 2.5 h after consuming NO3− and placebo. Placebo had no effect but NO3− led to an 8.6-fold increase in plasma NO2−, which was accompanied by an increase in FMD (NO3−: +1.18 ± 0.94% vs. placebo: 0.23 ± 1.13%, p = 0.002), and a reduction in AIx75 (NO3−: −8.7 ± 11.6% vs. placebo: −4.6 ± 5.5%, p = 0.027). PLM hyperaemia, BP, and PWV were unchanged during both trials. This study showed that a dose of dietary NO3− improved NO bioavailability and enhanced endothelial function as measured by femoral artery FMD. These findings provide insight into the specific central and peripheral vascular responses to dietary NO3− supplementation in older adult

Agreement between left and right middle cerebral artery blood velocity responses to incremental and constant work-rate exercise in healthy males and females

This is the author accepted manuscript. The final version is available from IOP Publishing via the DOI in this recordObjective: To quantify the agreement between left and right middle cerebral artery blood velocity (MCAv) responses to incremental and constant work-rate exercise in adults. Approach: Seventeen healthy adults (23.8±2.4 years, 9 females) completed a ramp incremental test to exhaustion on a cycle ergometer, three 6-minute transitions at a moderate-intensity, and three at a heavy-intensity, all on separate days. Bilateral MCAv was measured throughout using transcranial Doppler ultrasonography, with left and right MCAv data analysed separately. Data were analysed at baseline, gas exchange threshold, respiratory compensation point and exhaustion during ramp incremental exercise. MCAv responses to constant work-rate exercise were analysed using a mono-exponential model, to determine time- and amplitude-based kinetic response parameters. Main Results: Left and right MCAv responses to incremental and constant work-rate exercise were significantly, strongly and positively correlated (r≥0.61, P<0.01). Coefficient of variation (left vs right) ranged from 7.3-20.7%, 6.4-26.2% and 5.9-22.5% for ramp, moderate and heavy 33 intensity exercise, respectively. The relative change in MCAv from baseline was higher in the right compared to left MCAv during ramp, moderate and heavy-intensity exercise (all P<0.05), but the effect sizes were small (d≤0.4). Small mean left-right differences were present during ramp incremental exercise at all time-points (<6 cm/s; <4%), and for all kinetic parameters during moderate and heavy-intensity exercise (<3 cm/s, <3%, <4 s). Significance: These findings demonstrate similarities between left and right MCAv responses to incremental and constant-work rate exercise in adults on a group-level, but also highlight individual variation in the agreement between left and right MCAv exercise responsesQUEX Institut