Molecular biomarkers for assessing the heat-adapted phenotype: a narrative scoping review.

Heat acclimation/acclimatisation (HA) mitigates heat-related decrements in physical capacity and heat-illness risk and is a widely advocated countermeasure for individuals operating in hot environments. The efficacy of HA is typically quantified by assessing the thermo-physiological responses to a standard heat acclimation state test (i.e. physiological biomarkers), but this can be logistically challenging, time consuming, and expensive. A valid molecular biomarker of HA would enable evaluation of the heat-adapted state through the sampling and assessment of a biological medium. This narrative review examines candidate molecular biomarkers of HA, highlighting the poor sensitivity and specificity of these candidates and identifying the current lack of a single 'standout' biomarker. It concludes by considering the potential of multivariable approaches that provide information about a range of physiological systems, identifying a number of challenges that must be overcome to develop a valid molecular biomarker of the heat-adapted state, and highlighting future research opportunities.

Sex differences in response to exercise heat stress in the context of the military environment.

Women can now serve in ground close combat (GCC) roles, where they may be required to operate alongside men in hot environments. However, relative to the average male soldier, female soldiers are less aerobically fit, with a smaller surface area (A D), lower mass (m) with higher body fat and a larger A D/m ratio. This increases cardiovascular strain, reduces heat exchange with the environment and causes a greater body temperature increase for a given heat storage, although a large A D/m ratio can be advantageous. Physical employment standards for GCC roles might lessen the magnitude of fitness and anthropometric differences, yet even when studies control for these factors, women sweat less than men at high work rates. Therefore, the average female soldier in a GCC role is likely to be at a degree of disadvantage in many hot environments and particularly during intense physical activity in hot-arid conditions, although heat acclimation may mitigate some of this effect. Any thermoregulatory disadvantage may be exacerbated during the mid-luteal phase of the menstrual cycle, although the data are equivocal. Likewise, sex differences in behavioural thermoregulation and cognition in the heat are not well understood. Interestingly, there is often lower reported heat illness incidence in women, although the extent to which this is influenced by behavioural factors or historic differences in role allocation is unclear. Indeed, much of the extant literature lacks ecological validity and more work is required to fully understand sex differences to exercise heat stress in a GCC context.

In pursuit of the unicorn.

This short review was prompted by The Physiological Society's recent online symposium on variability. It does not deal with a specific methodology, but rather with the myth that certain environmentally-induced clinical conditions can be identified, quantified, simplified and monitored with a single methodology. Although this might be possible with some clinical conditions, others resist the prevailing reductionist approach of minimizing rather than exploring variation in pathogenesis and pathology, and will not be understood fully until the variation in cause and effect are embraced. This is likely to require comprehensive methodologies and collaboration.

Cold water immersion: kill or cure?

NEW FINDINGS: What is the topic of this review? This is the first review to look across the broad field of 'cold water immersion' and to determine the threats and benefits associated with it as both a hazard and a treatment. What advances does it highlight? The level of evidence supporting each of the areas reviewed is assessed. Like other environmental constituents, such as pressure, heat and oxygen, cold water can be either good or bad, threat or treatment, depending on circumstance. Given the current increase in the popularly of open cold water swimming, it is timely to review the various human responses to cold water immersion (CWI) and consider the strength of the claims made for the effects of CWI. As a consequence, in this review we look at the history of CWI and examine CWI as a precursor to drowning, cardiac arrest and hypothermia. We also assess its role in prolonged survival underwater, extending exercise time in the heat and treating hyperthermic casualties. More recent uses, such as in the prevention of inflammation and treatment of inflammation-related conditions, are also considered. It is concluded that the evidence base for the different claims made for CWI are varied, and although in most instances there seems to be a credible rationale for the benefits or otherwise of CWI, in some instances the supporting data remain at the level of anecdotal speculation. Clear directions and requirements for future research are indicated by this review.

The influence of a menthol and ethanol soaked garment on human temperature regulation and perception during exercise and rest in warm, humid conditions.

UNLABELLED: This study assessed whether donning a garment saturated with menthol and ethanol (M/E) can improve evaporative cooling and thermal perceptions versus water (W) or nothing (CON) during low intensity exercise and rest in warm, humid conditions often encountered in recreational/occupational settings. It was hypothesised there would be no difference in rectal (Tre) and skin (Tsk) temperature, infra-red thermal imagery of the chest/back, thermal comfort (TC) and rating of perceived exertion (RPE) between M/E, W and CON, but participants would feel cooler in M/E versus W or CON. METHODS: Six volunteers (mean [SD] 22 [4] years, 72.4 [7.4] kg and 173.6 [3.7] cm) completed (separate days) three, 60-min tests in 30°C, 70%rh, in a balanced order. After 15-min of seated rest participants donned a dry (CON) or 80mL soaked (M/E, W) long sleeve shirt appropriate to their intervention. They then undertook 30-min of low intensity stepping at a rate of 12steps/min on a 22.5cm box, followed by 15-min of seated rest. Measurements included heart rate (HR), Tre, Tsk (chest/back/forearm), thermal imaging (back/chest), thermal sensation (TS), TC and RPE. Data were reported every fifth minute as they changed from baseline and the area under the curves were compared by condition using one-way repeated measures ANOVA, with an alpha level of 0.05. RESULTS: Tre differed by condition, with the largest heat storage response observed in M/E (p<0.05). Skin temperature at the chest/back/forearm, and thermal imaging of the chest all differed by condition, with the greatest rate of heat loss observed in W and M/E respectively (p<0.01). Thermal sensation differed by condition, with the coolest sensations observed in M/E (p<0.001). No other differences were observed. CONCLUSIONS: Both M/E and W enhanced evaporative cooling compared CON, but M/E causes cooler sensations and a heat storage response, both of which are likely mediated by menthol.

Effect of short-term heat acclimation with permissive dehydration on thermoregulation and temperate exercise performance.

We examined the effect of short-term heat acclimation with permissive dehydration (STHADe) on heat acclimation (HA) and cycling performance in a temperate environment. Ten trained male cyclists [mean (SD) maximal oxygen uptake: 63.3(4.0) mL/kg/min; peak power output (PPO): 385(40) W; training: 10 (3) h/week] underwent a STHADe program consisting of 5 days of exercise (maximum 90 min/day) in a hot environment (40 °C, 50% RH) to elicit isothermic heat strain [rectal temperature 38.64(0.27) °C]. Participants abstained from fluids during, and 30 min after, HA sessions. Pre- and post-STHADe HA was evaluated during euhydrated fixed-intensity exercise (60 min) in hot conditions; the effect of STHADe on thermoregulation was also examined under temperate conditions (20 min fixed-intensity exercise; 22 °C, 60% RH). Temperate cycling performance was assessed by a graded exercise test (GXT) and 20-km time trial (TT). STHADe reduced thermal and cardiovascular strain in hot and temperate environments. Lactate threshold [Δ = 16 (17) W] and GXT PPO [Δ = 6 (7) W] were improved following STHADe (P < 0.05), but TT performance was not affected (P > 0.05), although there was a trend for a higher mean power (P = 0.06). In conclusion, STHADE can reduce thermal and cardiovascular strain under hot and temperate conditions and there is some evidence of ergogenic potential for temperate exercise, but longer HA regimens may be necessary for this to meaningfully influence performance.

Environmental extremes: origins, consequences and amelioration in humans.

Professor Sir George Lindor Brown (1903-1971) is known for his pioneering research into cholinergic neuromuscular transmission. However, during World War II he worked in hyperbaric physiology, and his research into underwater physiology greatly improved the safety of divers. It is perhaps fitting, therefore, that this review, which accompanies the Physiological Society's G. L. Brown Prize Lecture for 2015, explores the impact and mitigation of the environmental stresses which, to varying extents, have shaped our past, threaten our present and inform our future. From a whole-body, integrative perspective, this review examines our current understanding of microgravity, hypo- and hyperbaria, heat, cold air and cold water as both individual and combined stresses. Consideration is given to ways of mitigating the threat posed by environmental extremes, including the differing extents to which humans can demonstrate adaptation to them. Finally, recommendations for further study are suggested that might result in both direct and indirect insights.

Physiological cost and thermal envelope: a novel approach to cycle garment evaluation during a representative protocol.

This study aimed to examine thermoregulation in different clothing assemblies during a representative cycling exercise protocol. Six men undertook cycling exercise simulating representative thermal exchange challenges while wearing low (LOW), intermediate (INT1 and INT2), or high (HI) amounts of clothing. Exercise was conducted at 14.5 °C, 46.8% relative humidity and included a "flat" [45 min at 35% peak power output (PPO), wind speed 8.3 m/s], "uphill" (30 min at 55% PPO, wind speed 3.6 m/s), and "downhill" (20 min at 50 W, wind speed 16.7 m/s) stage. Rectal temperature changed with the exercise stage and was independent of clothing assembly. In contrast, an "envelope" was evident for mean body temperature, resulting from differences in mean skin temperature between the LOW and HI conditions. The elevated mean body temperature in HI was associated with increased physiological "cost," in the form of increased sweat production and heart rate. Physiological cost provides a better index of clothing performance than deep body temperature in the "thermoregulatory zone," as a consequence sports clothing should attempt to optimize the balance between comfort and reduced physiological cost.

The determinants of thermal comfort in cool water.

Water-based activities may result in the loss of thermal comfort (TC). We hypothesized that in cooling water, the hands and feet would be responsible. Supine immersions were conducted in up to five clothing conditions (exposing various regions), as well as investigations to determine if a "reference" skin temperature (Tsk) distribution in thermoneutral air would help interpret our findings. After 10 min in 34.5 °C water, the temperature was decreased to 19.5 °C over 20 min; eight resting or exercising volunteers reported when they no longer felt comfortable and which region was responsible. TC, rectal temperature, and Tsk were measured. Rather than the extremities, the lower back and chest caused the loss of overall TC. At this point, mean (SD) chest Tsk was 3.3 (1.7) °C lower than the reference temperature (P = 0.005), and 3.8 (1.5) °C lower for the back (P = 0.002). Finger Tsk was 3.1 (2.7) °C higher than the reference temperature (P = 0.037). In cool and cooling water, hands and feet, already adapted to colder air temperatures, will not cause discomfort. Contrarily, more discomfort may arise from the chest and lower back, as these regions cool by more than normal. Thus, Tsk distribution in thermoneutral air may help understand variations in TC responses across the body.

Physiological employment standards I. Occupational fitness standards: objectively subjective?

This paper examines the processes involved in the establishment of a minimum occupational fitness standard, with particular reference to the interplay that inevitably occurs between objective measurements and subjective decisions. The areas considered include: the determination of the critical task on which to base a standard; establishing minimum acceptable performance and methods of best practice for the execution of these tasks; determining the physical demands of a task and a reasonable relative workload; producing the final standard. Finally, the impact of the subjective component of the development of an occupational fitness standard on its defensibility is discussed. It is concluded that all standards involve some subjective aspects; the extent of these could be reduced by further research. In the meantime, it would be prudent for those developing standards to detail the rationale, methods and evidence by which subjective decisions were reached, to provide an audit trail for subsequent investigation.

Moderate hypoxia does not affect the zone of thermal comfort in humans.

The zone of thermal comfort was determined during normoxia and hypoxia in 15 healthy normothermic young subjects. Subjects dressed only in shorts/shorts and bikini top donned a water-perfused suit and assumed a supine position on a bench. The ambient temperature was maintained at a mean (SD) of 25.7 (0.3) degrees C. The thermal comfort zone was determined by increasing the temperature of the water perfusing the suit from cool to warm. During the heating process, subjects were instructed to report when their perception of the thermal stimulus provided by the suit changed from unpleasant to pleasant, and again from pleasant to unpleasant. The boundaries of the thermal comfort zone were assumed to be the temperatures of the water perfusing the suit at the time the subjects reported a change in the affective component of their thermal perception. In normoxia, subjects inspired room air and in hypoxia a gas mixture containing 10% O(2) in N(2). Tympanic temperature was similar in the normoxia and hypoxia conditions (P>0.05). The average (SD) lower and upper limits of the thermal comfort zone were 30.5 (1.5) and 34.7 (3.3) degrees C, respectively, during normoxia, and 30.5 (1.7) and 35.1 (3.4) degrees C, respectively, during hypoxia. No significant differences were observed between the normoxia and hypoxia conditions (P>0.05). Also, no gender-related differences were observed in the characteristics of the thermal comfort zone. The results of the present study indicate that acute hypoxic exposure simulated in the present study does not affect the zone of thermal comfort in humans.

Hypoxia increases the cutaneous threshold for the sensation of cold.

Cutaneous temperature sensitivity was tested in 13 male subjects prior to, during and after they breathed either a hypocapnic hypoxic (HH), or a normocapnic hypoxic (NH) breathing mixture containing 10% oxygen in nitrogen. Normocapnia was maintained by adding carbon dioxide to the inspired gas mixture. Cutaneous thresholds for thermal sensation were determined by a thermosensitivity testing device positioned on the plantar side of the first two toes on one leg. Heart rate, haemoglobin saturation, skin temperature at four sites (arm, chest, thigh, calf) and adapting temperature of the skin (T(ad); degrees centigrade), i.e. the temperature of the toe skin preceding a thermosensitivity test, were measured at minute intervals. Tympanic temperature (T(ty); degrees centigrade) was measured prior to the initial normoxic thermosensitivity test, during the hypoxic exposure and after the completion of the final normoxic thermosensitivity test. End-tidal carbon dioxide fraction and minute inspiratory volume were measured continuously during the hypoxic exposure. Ambient temperature, T(ty), T(ad) and mean skin temperature remained similar in both experimental conditions. Cutaneous sensitivity to cold decreased during both HH (P<0.001) and NH conditions (P<0.001) as compared with the tests undertaken pre- and post-hypoxia. No similar effect was observed for cutaneous sensitivity to warmth. The results of the present study suggest that sensitivity to cold decreases during the hypoxic exposure due to the effects associated with hypoxia rather than hypocapnia. Such alteration in thermal perception may affect the individual's perception of thermal comfort and consequently attenuate thermoregulatory behaviour during cold exposure at altitude.

Motion sickness potentiates core cooling during immersion in humans.

1. The present study tested the hypothesis that motion sickness affects thermoregulatory responses to cooling in humans. 2. Ten healthy male volunteers underwent three separate head-out immersions in 28 degrees C water after different preparatory procedures. In the 'control' procedure immersion was preceded by a rest period. In the 'motion sickness' procedure immersion was preceded by provocation of motion sickness in a human centrifuge. This comprised rapid and repeated alterations of the gravitational (G-) stress in the head-to-foot direction, plus a standardized regimen of head movements at increased G-stress. In the 'G-control' procedure, the subjects were exposed to similar G-stress, but without the motion sickness provocation. 3. During immersion mean skin temperature, rectal temperature, the difference in temperature between the forearm and 3rd digit of the right hand (DeltaT(forearm-fingertip)), oxygen uptake and heart rate were recorded. Subjects provided ratings of temperature perception, thermal comfort and level of motion sickness discomfort at regular intervals. 4. No differences were observed in any of the variables between control and G-control procedures. In the motion sickness procedure, the DeltaT(forearm-fingertip) response was significantly attenuated, indicating a blunted vasoconstrictor response, and rectal temperature decreased at a faster rate. No other differences were observed. 5. Motion sickness attenuates the vasoconstrictor response to skin and core cooling, thereby enhancing heat loss and the magnitude of the fall in deep body temperature. Motion sickness may predispose individuals to hypothermia, and have significant implications for survival time in maritime accidents.

Assessment of physical fitness for occupations encompassing load-carriage tasks.

There is increasing anecdotal evidence that simple occupational tests of aerobic fitness impose a systematic bias against heavier personnel when predicting fitness for load-carrying tasks. This study tested the hypothesis that simple field tests of aerobic fitness are not good predictors of load-carrying performance and that personnel with greater body mass are more able to perform occupationally relevant load-carrying tasks. Twelve healthy male volunteers ran on a level treadmill at 9.5 km/h for 4 min, with (T18) and without (T0) an external backpack load of 18 kg. During each exercise period, steady-state oxygen uptake (VO(2)) was assessed. On a subsequent occasion (at least 7 days later), 11 of the subjects ran to exhaustion at 9.5 km/h whilst carrying the 18 kg external load (ETT18). There was a strong inverse linear relationship between relative VO(2) and body mass (r = -0.87, P < 0.01) and between VO(2) and lean body mass (r = -0.74, P < 0.01) during the T18 trials. Furthermore, there was a moderately strong relationship between exercise time (ETT18) and body mass (r = 0.69, P < 0.05) and between exercise time and lean body mass (r = 0.71, P < 0.05). There was no relationship between exercise tolerance time and VO(2) (r = 0.12). The results show that fitness tests that determine aerobic power in units relative to body mass (e.g. timed distance run) incur a systematic bias against heavier personnel. Such tests are therefore inappropriate when predicting the ability of personnel to work in occupations that encompass load-carrying tasks.

Thermal status of saturation divers during operational dives in the North Sea.

The principal aim of the present study was to monitor the core temperature (Tc) of a population of saturation divers conducting routine deep dives at different locations in the United Kingdom sector of the North Sea and to assess whether current dive procedures are adequate in preventing deleterious decreases in Tc. A total of 30 divers, with an average (SD) of 19.3 (6.6) yr of experience as saturation divers, participated in the study. The survey included 59 dives conducted at six locations (Scott Field, Norfra Pipeline, Hudson Field, Pierce Field, Forties Field, and Bruce Field) from four Diver Support Vessels (Rockwater 1, Semi 2, Bar Protector, and Discovery). The depth of the dives monitored ranged from 54 to 160 meters of seawater (msw), and the duration of the dives from 31 min to 7 h 30 min. before each dive, divers were requested to ingest a radio pill and strap a data logger to their abdomen. Upon returning to the chamber within the Diver Support Vessel following a dive, they provided subjective ratings of thermal perception (7 point scale) and thermal comfort (4 point scale) for the period just before, during, and immediately after the dive. In 55 dives, Tc of saturation divers working at depths to 160 msw for up to 6 h with water temperatures ranging from 4 degrees to 6 degrees C increased above the pre-dive core temperature of 37.4 degrees (0.620+/-0.6 degrees C). In four dives there was a decrease in Tc: 2 divers had a 0.2 degrees C fall in Tc, and 2 bellmen had a decrease of 0.4 degrees and 1.0 degrees C. The subjective responses of divers indicated that they were thermally neutral (neither warm nor cold) and comfortable before and immediately after the dives. The current practice of providing thermal protection with hot water suits to saturation divers working in the North Sea is adequate for preventing the risk of hypothermia and maintaining thermal comfort.

Permanence of the habituation of the initial responses to cold-water immersion in humans.

Sudden immersion in cold water initiates an inspiratory gasp response followed by uncontrollable hyperventilation and tachycardia. It is known that this response, termed the "cold shock" response, can be attenuated following repeated immersion. In the present investigation we examined how long this habituation lasts. Twelve healthy male volunteers participated in the experiment, they were divided into a control (C) group (n = 4), and a habituation (H) group (n = 8). In October, each subject undertook two 3-min head-out seated immersions into stirred water at 10 degrees C wearing swimming trunks. These immersions took place at the same time of day, with 4 days separating the two immersions. In the intervening period, the C group were not exposed to cold water, while the H group undertook six, 3-min head-out immersions in water at 15 degrees C. Two months (December), 4 months (February), 7 months (May) and 14 months (January) after their first immersion, all subjects undertook another 3-min head-out immersion in water at 10 degrees C. The H group showed a reduction in respiratory frequency (47 to 24 breaths x min(-1)), inspiratory minute volume (72.2 to 31.3 1 x min(-1)) and heart rate (128 to 109 beats x min(-1)) during the first 30 s of immersion on day 5 compared to day 1. Seven months later these responses were still significantly reduced compared to day 1. After 14 months, heart rate remained attenuated but respiratory frequency and inspiratory minute volume had returned towards pre-habituation levels. The responses of the C group during the first 30 s of immersion were not altered. Both groups showed an attenuation in the responses during the remaining 150 s of immersion following repeated immersions. It is concluded that repeated immersions in cold water result in a longlasting (7-14 months) reduction in the magnitude of the cold shock response. Less frequent immersions produced a decrease in the duration, but not the magnitude of the response.

Habituation of the initial responses to cold water immersion in humans: a central or peripheral mechanism?

1. The initial respiratory and cardiac responses to cold water immersion are thought to be responsible for a significant number of open water deaths each year. Previous research has demonstrated that the magnitude of these responses can be reduced by repeated immersions in cold waterwhether the site of habituation is central or peripheral. 2. Two groups of subjects undertook two 3 min head-out immersions in stirred water at 10 C of the right-hand side of the body (R). Between these two immersions (3 whole days) the control group (n = 7) were not exposed to cold water, but the habituation group (n = 8) undertook a further six 3 min head-out immersions in stirred water at 10 C of the left-hand side of the body (L). 3. Repeated L immersions reduced (P < 0.01) the heart rate, respiratory frequency and volume responses. During the second R immersion a reduction (P < 0.05) in the magnitude of the responses evoked was seen in the habituation group but not in the control group, despite both groups having identical skin temperature profiles. 4. It is concluded that the mechanisms involved in producing habituation of the initial responses are located more centrally than the peripheral receptors.

Temperature dependence of habituation of the initial responses to cold-water immersion.

The initial responses to cold-water immersion, evoked by stimulation of peripheral cold receptors, include tachycardia, a reflex inspiratory gasp and uncontrollable hyperventilation. When immersed naked, the maximum responses are initiated in water at 10 degrees C, with smaller responses being observed following immersion in water at 15 degrees C. Habituation of the initial responses can be achieved following repeated immersions, but the specificity of this response with regard to water temperature is not known. Thirteen healthy male volunteers were divided into a control (C) group (n = 5) and a habituation (H) group (n = 8). Each subject undertook two 3-min head-out immersions in water at 10 degrees C wearing swimming trunks. These immersions took place at a corresponding time of day with 4 days separating the two immersions. In the intervening period the C group were not exposed to cold water, while the H group undertook another six, 3-min, head-out immersions in water at 15 degrees C. Respiratory rate (fR), inspiratory minute volume (VI) and heart rate (fH) were measured continuously throughout each immersion. Following repeated immersions in water at 15 degrees C, the fR, VI and fH responses of the H group over the first 30 s of immersion were reduced (P < 0.01) from 33.3 breaths x min(-1), 50.5 l x min(-1) and 114 beats x min(-1) respectively, to 19.8 breaths x min(-1) 26.41 x min(-1) and 98 beats x min(-1), respectively. In water at 10 degrees C these responses were reduced (P < 0.01) from 47.3 breaths x min(-1), 67.61 x min(-1) and 128 beats x min(-1) to 24.0 breaths x min(-1), 29.5 l x min(-1) and 109 beats x min(-1), respectively over a corresponding period of immersion. Similar reductions were observed during the last 2.5 min of immersions. The initial responses of the C group were unchanged. It is concluded that habituation of the cold shock response can be achieved by immersion in warmer water than that for which protection is required. This suggests that repeated submaximal stimulation of the cutaneous cold receptors is sufficient to attenuate the responses to more maximal stimulation.