Dr Steve Trangmar

Claude Bernard’s milieu intérieur (internal environment) and the associated concept of homeostasis are fundamental to the understanding of the physiological responses to exercise and environmental stress. Maintenance of cellular homeostasis is thought to happen during exercise through the precise matching of cellular energetic demand and supply, and the production and clearance of metabolic by-products. The mind-boggling number of molecular and cellular pathways and the host of tissues and organ systems involved in the processes sustaining locomotion, however, necessitate an integrative examination of the body’s physiological systems. This integrative approach can be used to identify whether function and cellular homeostasis are maintained or compromised during exercise. In this review, we discuss the responses of the human brain, the lungs, the heart, and the skeletal muscles to the varying physiological demands of exercise and environmental stress. Multiple alterations in physiological function and differential homeostatic adjustments occur when people undertake strenuous exercise with and without thermal stress. These adjustments can include: hyperthermia; hyperventilation; cardiovascular strain with restrictions in brain, muscle, skin and visceral organs blood flow; greater reliance on muscle glycogen and cellular metabolism; alterations in neural activity; and, in some conditions, compromised muscle metabolism and aerobic capacity. Oxygen supply to the human brain is also blunted during intense exercise, but global cerebral metabolism and central neural drive are preserved or enhanced. In contrast to the strain seen during severe exercise and environmental stress, a steady state is maintained when humans exercise at intensities and in environmental conditions that require a small fraction of the functional capacity. The impact of exercise and environmental stress upon whole-body functions and homeostasis therefore depends on the functional needs and differs across organ systems.

Metabolic syndrome (MetS) is a global public health problem affecting nearly 25.9% of the world population characterised by a cluster of disorders dominated by abdominal obesity, high blood pressure, high fasting plasma glucose, hypertriacylglycerolaemia and low HDL-cholesterol. In recent years, marine organisms, especially seaweeds, have been highlighted as potential natural sources of bioactive compounds and useful metabolites, with many biological and physiological activities to be used in functional foods or in human nutraceuticals for the management of MetS and related disorders. Of the three groups of seaweeds, brown seaweeds are known to contain more bioactive components than either red and green seaweeds. Among the different brown seaweed species, Ascophyllum nodosum and Fucus vesiculosus have the highest antioxidant values and highest total phenolic content. However, the evidence base relies mainly on cell line and small animal models, with few studies to date involving humans. This review intends to provide an overview of the potential of brown seaweed extracts Ascophyllum nodosum and Fucus vesiculosus for the management and prevention of MetS and related conditions, based on the available evidence obtained from clinical trials.

An approach that combines weight loss with additional health benefits is very desirable. Glucomannan is a dietary fibre that expands in the stomach, creating the feeling of fullness, while chromium can regulate insulin response. Oligofructose is a non-digestible prebiotic fibre with well-established bifidogenic properties that may also have a role in regulating satiety and systemic inflammation. The aim of this 4-week pilot human intervention was to investigate the effect of agglomerated glucomannan, oligofructose and chromium, as part of a calorie restricted diet plan, on weight loss, satiety, satiation, mood and gut microbiota in 12 females (18–65 years, BMI 25–35 kg/m

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Limb tissue and systemic blood flow increases with heat stress, but the underlying mechanisms remain poorly understood. Here, we tested the hypothesis that heat stress-induced increases in limb tissue perfusion are primarily mediated by local temperature-sensitive mechanisms. Leg and systemic temperatures and hemodynamics were measured at rest and during incremental single-legged knee extensor exercise in 15 males exposed to 1 h of either systemic passive heat-stress with simultaneous cooling of a single leg ( n = 8) or isolated leg heating or cooling ( n = 7). Systemic heat stress increased core, skin and heated leg blood temperatures (Tb), cardiac output, and heated leg blood flow (LBF; 0.6 ± 0.1 l/min; P < 0.05). In the cooled leg, however, LBF remained unchanged throughout ( P > 0.05). Increased heated leg deep tissue blood flow was closely related to Tb ( R2 = 0.50; P < 0.01), which is partly attributed to increases in tissue V̇O2 ( R2 = 0.55; P < 0.01) accompanying elevations in total leg glucose uptake ( P < 0.05). During isolated limb heating and cooling, LBFs were equivalent to those found during systemic heat stress ( P > 0.05), despite unchanged systemic temperatures and hemodynamics. During incremental exercise, heated LBF was consistently maintained ∼0.6 l/min higher than that in the cooled leg ( P < 0.01), with LBF and vascular conductance in both legs showing a strong correlation with their respective local Tb ( R2 = 0.85 and 0.95, P < 0.05). We conclude that local temperature-sensitive mechanisms are important mediators in limb tissue perfusion regulation both at rest and during small-muscle mass exercise in hyperthermic humans.

Abstract

Cardiovascular strain and hyperthermia are thought to be important factors limiting exercise capacity in heat‐stressed humans, however, the contribution of elevations in skin (Tsk) versus whole body temperatures on exercise capacity has not been characterized. To ascertain their relationships with exercise capacity, blood temperature (TB), oxygen uptake (V̇O2), brain perfusion (MCA Vmean), locomotor limb hemodynamics, and hematological parameters were assessed during incremental cycling exercise with elevated skin (mild hyperthermia; HYPmild), combined core and skin temperatures (moderate hyperthermia; HYPmod), and under control conditions. Both hyperthermic conditions increased Tsk versus control (6.2 ± 0.2°C; P < 0.001), however, only HYPmod increased resting TB, leg blood flow and cardiac output (Q̇), but not MCA Vmean. Throughout exercise, Tsk remained elevated in both hyperthermic conditions, whereas only TB was greater in HYPmod. At exhaustion, oxygen uptake and exercise capacity were reduced in HYPmod in association with lower leg blood flow, MCA Vmean and mean arterial pressure (MAP), but similar maximal heart rate and TB. The attenuated brain and leg perfusion with hyperthermia was associated with a plateau in MCA and two‐legged vascular conductance (VC). Mechanistically, the falling MCA VC was coupled to reductions in PaCO2, whereas the plateau in leg vascular conductance was related to markedly elevated plasma [NA] and a plateau in plasma ATP. These findings reveal that whole‐body hyperthermia, but not skin hyperthermia, compromises exercise capacity in heat‐stressed humans through the early attenuation of brain and active muscle blood flow.

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.

People undertaking prolonged vigorous exercise experience substantial bodily fluid losses due to thermoregulatory sweating. If these fluid losses are not replaced, endurance capacity may be impaired in association with a myriad of alterations in physiological function, including hyperthermia, hyperventilation, cardiovascular strain with reductions in brain, skeletal muscle and skin blood perfusion, greater reliance on muscle glycogen and cellular metabolism, alterations in neural activity and, in some conditions, compromised muscle metabolism and aerobic capacity. The physiological strain accompanying progressive exercise-induced dehydration to a level of ~ 4% of body mass loss can be attenuated or even prevented by: (1) ingesting fluids during exercise, (2) exercising in cold environments, and/or (3) working at intensities that require a small fraction of the overall body functional capacity. The impact of dehydration upon physiological function therefore depends on the functional demand evoked by exercise and environmental stress, as cardiac output, limb blood perfusion and muscle metabolism are stable or increase during small muscle mass exercise or resting conditions, but are impaired during whole-body moderate to intense exercise. Progressive dehydration is also associated with an accelerated drop in perfusion and oxygen supply to the human brain during submaximal and maximal endurance exercise. Yet their consequences on aerobic metabolism are greater in the exercising muscles because of the much smaller functional oxygen extraction reserve. This review describes how dehydration differentially impacts physiological function during exercise requiring low compared to high functional demand, with an emphasis on the responses of the human brain, heart and skeletal muscles.

The aim of the present study was to assess the effects of prior ingestion of coconut water on fluid retention and exercise capacity in the heat as well as signs of gastrointestinal distress. Eight physically active men were recruited (age 23 ± 3 years, height 176 ± 6 cm, body mass 78 ± 7 kg) and performed three exercise capacity trials on a cycle ergometer in the heat (34 ± 1°C) after the ingestion of one of the following drinks: a) plain water (PW), b) flavored drink (FD), and c) coconut water (CW). Ingestion of CWresulted in a longer time to exhaustion (p=0.029). Likewise, participants achieved a higher heart rate in the CW session when compared to the other trials (PW 183 ± 5 bpm, FD 184 ± 8 bpm, and CW 189 ± 8 bpm, p<0.05) and a reduced urine output after the coconut water ingestion (PW 214 ± 85 ml, FD 267 ± 90 ml, and CW 161 ± 73 ml, p<0.05) indicating a higher fluid retention of coconut water in comparison to plain water and the flavored drink. These results demonstrate that previous ingestion of coconut water improves exercise capacity in the heat and provide a reduced urine output in comparison to plain water and flavored drink. Also there is no evidence for GI distress.

Purpose To investigate the effects of 60 min daily, short-term (STHA) and medium-term (MTHA) isothermic heat acclimation (HA) on the physiological and perceptual responses to exercise heat stress. Methods Sixteen, ultra-endurance runners (female = 3) visited the laboratory on 13 occasions. A 45 min sub-maximal (40% Wmax) cycling heat stress test (HST) was completed in the heat (40 °C, 50% relative humidity) on the first (HSTPRE), seventh (HSTSTHA) and thirteenth (HSTMTHA) visit. Participants completed 5 consecutive days of a 60 min isothermic HA protocol (target Tre 38.5 °C) between HSTPRE and HSTSTHA and 5 more between HSTSTHA and HSTMTHA. Heart rate (HR), rectal (Tre), skin (Tsk) and mean body temperature (Tbody), perceived exertion (RPE), thermal comfort (TC) and sensation (TS) were recorded every 5 min. During HSTs, cortisol was measured pre and post and expired air was collected at 15, 30 and 45 min. Results At rest, Tre and Tbody were lower in HSTSTHA and HSTMTHA compared to HSTPRE, but resting HR was not different between trials. Mean exercising Tre, Tsk, Tbody, and HR were lower in both HSTSTHA and HSTMTHA compared to HSTPRE. There were no differences between HSTSTHA and HSTMTHA. Perceptual measurements were lowered by HA and further reduced during HSTMTHA. Conclusion A 60 min a day isothermic STHA was successful at reducing physiological and perceptual strain experienced when exercising in the heat; however, MTHA offered a more complete adaptation.

Introduction: Classical estimations suggest that non-exercising limb tissue and skin blood flow is progressively reduced through to volitional exhaustion (Rowell, 1974) associated with the exponential rise in sympathetic nerve activity and circulating catecholamines (Rosenmeier et al., 2004; Ichinose et al., 2008; Trangmar et al., 2014, 2017). However, there is no direct evidence that skin perfusion decreases during maximal aerobic exercise. Aims and objectives: The aim of the present study was to investigate the non-exercising limb tissue and skin hemodynamic and oxygenation responses to a range of exercise intensities and durations in the heat (35 °C, rH 50%; fan cooling). Methods: Blood oxygen content, O2 saturation, and arterio-venous oxygen difference (a-vO2 diff) in the inactive forearm were initially measured in nine endurance-trained males during three incremental cycling exercise tests to volitional exhaustion (Wpeak, 322 ± 38 W), with test 1 and 2 separated by a 2 hbout of constant load cycling (55% Wpeak). Forearm (brachial artery) blood flow (FBF), muscle oxygen saturation (mO2Sat), skin blood flow (SkBF) and a-vO2 diff, and body temperatures were assessed in a further seven endurance-trained males using the same experimental protocol. Data (presented as mean + SD) were assessed using repeated measures ANOVA, with the alpha level for significance set at P<0.05. Results: In incremental exercise tests 1 & 3, FBF was stable from rest to ~40% Wpeak, before increasing to a peak of 285 + 52 ml/min at 80% Wpeak (N=7, P<0.001). Concomitantly, skin a-vO2 diff, decreased from a baseline rest value of 56±27 mL/L to a nadir of ~25±27 mL/L at 80% Wpeak (N=9, P<0.05), remaining at this level through to Wpeak. SkBF increased, whilst mO2Sat decreased at intensities above 80% Wpeak. In incremental exercise test 2, that followed shortly after constant load exercise, baseline FBF was 3-fold higher than tests 1 & 3 (449 + 153 vs. 157 + 59 ml/min; N=9, P<0.01), remaining at this high level throughout, whilst skin a-vO2 diff was suppressed to a low level, and remained constant, compared to tests 1 & 3. Similar changes were observed during constant load exercise, with a rise in FBF mirrored by a fall in a-vO2 diff, concomitant to a high skin blood flow, and elevated core temperature. Conclusions: Skin perfusion and oxygen delivery remain elevated during incremental lower-limb exercise to volitional exhaustion in the heat. Moreover, differential haemodynamic and oxygenation responses in the tissues of the inactive-forearm occur during strenuous exercise in the heat, where 1) skin blood flow and oxygenation increase and remain high, concurrent to proportional reductions in skin a-vO2 diff and 2) muscle oxygenation declines during high-intensity exercise, indicating that increased forearm blood flow reflects the skin. These findings support observations in cool environmental conditions (Calbet et al., 2007; Kirby et al., 2021), and argue against the idea that increases in sympathoadrenal activity reduce skin perfusion during strenuous exercise. Ethical standards: All procedures were approved by the Brunel University London Research Ethics Committee and conformed to the ethical principles of the World Medical Association (Declaration of Helsinki).

Objectives To investigate the effects of pre- and per-cooling interventions on subsequent 15-min time-trial (TT) cycling performance in the heat. Design Randomized cross-over design. Methods Nine male athletes completed four experimental trials in the heat (40 °C, 50% rh): no-cooling (CON); warm-up per-cooling (PER: neck-cooling collar applied during the preload); pre-cooling (PRE: 30 min of cold water (22 °C) immersion [CWI]); and pre- and per-cooling combined (PRE + PER). In each trial, participants completed a 45-min preload exercise (50% V̇O2peak), followed by a 15-min TT. Physiological (rectal [Tre], skin [Tsk], and neck [Tneck] temperature, and heart rate [HR]) and perceptual data (ratings of perceived exertion [RPE], thermal comfort [TC] and thermal sensation [TS]) were measured throughout. Results Tre and Tsk were lower in PRE and PRE + PER at the start of the preload (p < 0.001). Tre remained lower throughout the preload following CWI although these differences were no longer present at the start of the TT (p = 0.22). Tneck was lowered throughout in PER and PRE + PER (p < 0.001). No other physiological or perceptual differences were observed at the start or end of the preload or TT. Participants covered a similar TT distance in all trials (15.7–15.9 km, p = 0.77). Conclusions Pre-cooling induced thermoregulatory benefits for ~45 min and perceptual benefits for the same duration when supplemented with per-cooling. Neck per-cooling offered no such benefits when used in isolation. Neither pre- nor per-cooling, in isolation or combination, improved subsequent 15-min cycling time-trial performance in well-trained participants in the heat (40 °C).

Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2(CMRO2) is preserved. It remains unknown whether CMRO2is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2. In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration ( P < 0.05). However, cerebral metabolism remained stable through enhanced O2and glucose extraction ( P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2.

Exercise-induced dehydration can lead to impaired perfusion to multiple regional tissues and organs. We propose that the impact of dehydration on regional blood flow and metabolism is dependent on the extent of the cardiovascular demand imposed by exercise, with the greatest physiological strain seen when approaching cardiovascular and aerobic capacities.

Blood flow in the inactive limb tissues and skin is widely thought to decline during incremental exercise to exhaustion due to augmented sympathoadrenal vasoconstrictor activity, but direct evidence to support this view is lacking. Here, we investigated the inactive-forearm haemodynamic (Q̇forearm) and oxygenation responses to a range of two-leg exercise intensities and durations in the heat. Blood oxygen and flow were measured in the forearm tissue and skin of endurance-trained males during three incremental cycling exercise tests, with tests 1 and 2 separated by a 2 h-bout of moderate constant load cycling exercise, all performed in the heat (35 °C, 50% rH, with fan cooling). In incremental exercise tests 1 and 3, Q̇forearm was stable from rest to ~40% Wpeak, before increasing by ~118% at 80% Wpeak (P < 0.001). Correspondingly, forearm skin arterio-venous oxygen difference (a-vO2 diff) decreased by ~62% at 80% Wpeak (P = 0.043), remaining reduced through to Wpeak. Concomitantly, forearm skin blood flow more than doubled, while forearm tissue O2 saturation decreased. When incremental exercise started shortly after constant load exercise (test 2), Q̇forearm was 2-3-fold higher than during tests 1 and 3, whereas skin a-vO2 diff was suppressed to a low level. Similar changes were observed during constant load exercise. In conclusion, skin perfusion increases during incremental exercise in the heat, concomitant to proportional reductions in oxygen extraction from the cutaneous circulation. Hence, contrary to the generally held view, skin perfusion remains elevated during maximal exercise and heat stress despite profound increases in sympathoadrenal activity.

Progressive whole-body hyperthermia with passive heat stress is associated with a host of physiological adjustments. These include large increases in peripheral blood flow and cardiac output and a smaller selective redistribution of blood flow from the cerebral and visceral tissues to the limbs, head, and torso, with perfusion pressure being only slightly reduced. Aerobic metabolism also increases in these conditions, but the magnitude is small in absolute terms, suggesting a predominant role of thermosensitive mechanisms in passive hyperthermia-induced cardiovascular adjustments. Although exercise heat stress requires substantially greater blood flow requirements compared to passive heat stress alone, the magnitude of this hyperemic response is less than would be expected given the extent to which both conditions independently increase blood flow in isolation. As a result, submaximal exercise limb blood flow is only slightly higher during small muscle-mass exercise in the heat, and is similar to control conditions during whole-body exercise. When exercise intensity is increased further towards maximal levels, the superimposition of heat stress leads to earlier reductions in regional and systemic blood perfusion, compromised locomotor limb aerobic metabolism, and ultimately results in impaired endurance capacity. This chapter provides an integrative overview of the human cardiovascular response to passive heat stress and exercise heat stress, with emphasis on its consequences on exercise performance in the heat.

Abstract

Intense, large muscle mass exercise increases circulating microvesicles, but our understanding of microvesicle dynamics and mechanisms inducing their release remains limited. However, increased vascular shear stress is generally thought to be involved. Here, we manipulated exercise‐independent and exercise‐dependent shear stress using systemic heat stress with localized single‐leg cooling (low shear) followed by single‐leg knee extensor exercise with the cooled or heated leg (Study 1, n = 8) and whole‐body passive heat stress followed by cycling (Study 2, n = 8). We quantified femoral artery shear rates (SRs) and arterial and venous platelet microvesicles (PMV–CD41+) and endothelial microvesicles (EMV–CD62E+). In Study 1, mild passive heat stress while one leg remained cooled did not affect [microvesicle] (P ≥ 0.05). Single‐leg knee extensor exercise increased active leg SRs by ~12‐fold and increased arterial and venous [PMVs] by two‐ to threefold, even in the nonexercising contralateral leg (P < 0.05). In Study 2, moderate whole‐body passive heat stress increased arterial [PMV] compared with baseline (mean±SE, from 19.9 ± 1.5 to 35.5 ± 5.4 PMV.μL−1.103, P < 0.05), and cycling with heat stress increased [PMV] further in the venous circulation (from 27.5 ± 2.2 at baseline to 57.5 ± 7.2 PMV.μL−1.103 during cycling with heat stress, P < 0.05), with a tendency for increased appearance of PMV across exercising limbs. Taken together, these findings demonstrate that whole‐body heat stress may increase arterial [PMV], and intense exercise engaging either large or small muscle mass promote PMV formation locally and systemically, with no influence upon [EMV]. Local shear stress, however, does not appear to be the major stimulus modulating PMV formation in healthy humans.

Heat stress, leading to elevations in whole-body temperature, has a marked impact on both physical performance and cognition in ecological settings. Lab experiments confirm this for physically demanding activities, whereas observations are inconsistent for tasks involving cognitive processing of information or decision-making prior to responding. We hypothesized that divergences could relate to task complexity and developed a protocol consisting of 1) simple motor task [TARGET_pinch], 2) complex motor task [Visuo-motor tracking], 3) simple math task [MATH_type], 4) combined motor-math task [MATH_pinch]. Furthermore, visuo-motor tracking performance was assessed both in a separate- and a multipart protocol (complex motor tasks alternating with the three other tasks). Following familiarization, each of the 10 male subjects completed separate and multipart protocols in randomized order in the heat (40°C) or control condition (20°C) with testing at baseline (seated rest) and similar seated position, following exercise-induced hyperthermia (core temperature ∼ 39.5°C in the heat and 38.2°C in control condition). All task scores were unaffected by control exercise or passive heat exposure, but visuo-motor tracking performance was reduced by 10.7 ± 6.5% following exercise-induced hyperthermia when integrated in the multipart protocol and 4.4 ± 5.7% when tested separately (both P < 0.05). TARGET_pinch precision declined by 2.6 ± 1.3% (P < 0.05), while no significant changes were observed for the math tasks. These results indicate that heat per se has little impact on simple motor or cognitive test performance, but complex motor performance is impaired by hyperthermia and especially so when multiple tasks are combined.

Longer heat acclimation (HA) protocols more effectively improve physical performance than shorter ones, but the effect of HA duration on cognitive performance remains unclear. Twelve participants performed a 45-min cycling heat stress test [(HST) 40%Wmax; 40°C; 50% RH] on the first (HST1), seventh (HST7), and thirteenth (HST13) day of testing with five consecutive days of isothermic HA (60-min; rectal temperature ~38.5°C) between each HST. Simple (five-choice reaction time [RT]) and complex (spatial working memory [SWM]) tests were completed before and after each HST. Reaction and Movement times were slower before HST13 than HST1. Fewer errors were made in the SWM test before HST13 in the 6- (0.0v2.7), 8- (1.8v7.6) and 12- (18v31) box tests and before HST7 in the 6- and 8-box tests (1.9v7.6) compared to HST1. Search strategy was improved before HST7 (4.5v6.8) and HST13 (4.3v6.8). Fewer errors were made in the 8-box test after HST7 (1.6v8.8) and HST13 (1.1v8.6). No other differences were observed (p > 0.05). HA improved performance in some of the more challenging tasks but had no effect on the most complex task (12-box) when physiological strain was highest. 10-days of HA was more effective than 5-days at improving some aspects of cognitive performance.