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Muscle-Damaging Exercise Increases Heat Strain during Subsequent Exercise Heat Stress

FORTES, MATTHEW BENJAMIN1; DI FELICE, UMBERTO1,2; DOLCI, ALBERTO1; JUNGLEE, NAUSHAD A.1; CROCKFORD, MICHAEL J.1; WEST, LIAM1; HILLIER-SMITH, RYAN1; MACDONALD, JAMIE HUGO1; WALSH, NEIL PETER1

Medicine & Science in Sports & Exercise: October 2013 - Volume 45 - Issue 10 - p 1915–1924
doi: 10.1249/MSS.0b013e318294b0f8
BASIC SCIENCES
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Purpose It remains unclear whether exercise-induced muscle damage (EIMD) increases heat strain during subsequent exercise heat stress, which in turn may increase the risk of exertional heat illness. We examined heat strain during exercise heat stress 30 min after EIMD to coincide with increases in circulating pyrogens (e.g., interleukin-6 [IL-6]) and 24 h after EIMD to coincide with the delayed muscle inflammatory response when a higher rate of metabolic energy expenditure () and thus decreased economy might also increase heat strain.

Methods Thirteen non–heat-acclimated males (mean ± SD, age = 20 ± 2 yr) performed exercise heat stress tests (running for 40 min at 65% V˙O2max in 33°C, 50% humidity) 30 min (HS1) and 24 h (HS2) after treatment, involving running for 60 min at 65% V˙O2max on either −10% gradient (EIMD) or +1% gradient (CON) in a crossover design. Rectal (Tre) and skin (Tsk) temperature, local sweating rate, and were measured throughout HS tests.

Results Compared with CON, EIMD evoked higher circulating IL-6 pre-HS1 (P < 0.01) and greater plasma creatine kinase and muscle soreness pre-HS2 (P < 0.01). The ΔTre was greater after EIMD than CON during HS1 (0.35°C, 95% confidence interval = 0.11°C–0.58°C, P < 0.01) and HS2 (0.17°C, 95% confidence interval = 0.07°C–0.28°C, P < 0.01). was higher on EIMD throughout HS1 and HS2 (P < 0.001). Thermoeffector responses (Tsk, sweating rate) were not altered by EIMD. Thermal sensation and RPE were higher on EIMD after 25 min during HS1 (P < 0.05). The final Tre during HS1 correlated with the pre-HS1 circulating IL-6 concentration (r = 0.67).

Conclusions Heat strain was increased during endurance exercise in the heat conducted 30 min after and, to a much lesser extent, 24 h after muscle-damaging exercise. These data indicate that EIMD is a likely risk factor for exertional heat illness particularly during exercise heat stress when behavioral thermoregulation cues are ignored.

1College of Health and Behavioural Sciences, Bangor University, Gwynedd, UNITED KINGDOM; and 2Department of Biomedical Sciences and Technologies, University of L’Aquila, Coppito, ITALY

Address for correspondence: Neil Peter Walsh, Ph.D., Extremes Research Group, College of Health and Behavioural Sciences, Bangor University, Bangor, LL57 2PZ, United Kingdom; E-mail: n.walsh@bangor.ac.uk.

Submitted for publication December 2012.

Accepted for publication March 2013.

Athletes and military personnel undergoing heavy training are often expected to perform repeated bouts of arduous physical activity on the same day, often in hot environments, which may predispose them to exertional heat illness (EHI) or the more serious form, and often fatal, exertional heat stroke (EHS) (11,38). Several traditional risk factors have been identified for EHI and EHS such as hot and humid environmental conditions, inappropriate clothing, lack of heat acclimation, sleep disruption, high exercise intensity, high body mass index, low physical fitness, and underlying medical conditions (2,19,34). Nevertheless, these traditional risk factors do not account for all EHI cases, suggesting that other lesser known risk factors and pathways may play a role in many cases of EHI (38). An additional pathway for the development of EHI has been proposed that involves a systemic inflammatory response (4,24,39), with an increase in pyrogenic cytokines (e.g., interleukin [IL]-1β, IL-6, and tumor necrosis factor α), which may accelerate the progression of the individual toward EHI and/or EHS (41). In support of this notion, the febrile response to LPS injection was abolished in rodents pretreated with anti-IL-6 antibodies (10,37), and rodents injected with IL-1 receptor antagonist demonstrated improved survival after experimental heatstroke (13). Evidence also exists that exercise itself has a pyrogenic effect similar to that of fever. For example, postexercise plasma drawn from humans induced fever in rodents, in contrast to preexercise plasma that did not (9). In addition, 6 d of supplementation with the cycloxygenase inhibitor rofecoxib blunted the increase in body temperature during prolonged exercise in humans, suggesting that prostaglandin-mediated inflammatory processes may also contribute to increased heat strain during exercise (5).

It remains unclear whether exercise-induced muscle damage (EIMD) increases heat strain during subsequent exercise heat stress, which in turn may increase the risk of EHI. Exercising muscle releases the inflammatory cytokine IL-6 (20), and it has been demonstrated that EIMD elicits a greater circulating IL-6 response than non–muscle-damaging concentric exercise (7). Therefore, it is plausible that EIMD and associated inflammation (increase in circulating pyrogenic cytokines) might increase heat strain at least in the short-term during subsequent exercise heat stress. The muscle soreness that typically peaks 24–48 h after EIMD might also increase heat strain during walking and running by increasing the rate of metabolic energy expenditure (decreased economy) as a consequence of alterations in gait and motor unit recruitment because of muscle stiffness and/or weakness (25). To the best of our knowledge, only one published study has attempted to investigate these possibilities, albeit the experimental model elicited relatively modest heat strain (25). Core body temperature was 0.2°C–0.3°C higher at 2 and 7 h but was not altered 26 h, after lower body muscle-damaging exercise (eccentric component of leg press and leg curl) (25). The authors attributed a large proportion of the EIMD-evoked increase in core body temperature during exercise heat stress to decreased economy but recognized that other factors such as the inflammatory response likely play a part. Unfortunately, the muscle-damaging protocol did not elicit a significant increase in circulating inflammatory markers (e.g., the pyrogen IL-6) before the exercise heat challenge 2 h after muscle injury and only a small increase 7 h after injury. As such, it remains unclear whether the acute circulating inflammatory response that follows EIMD contributes to greater heat strain during subsequent exercise heat stress. In addition, from a practical perspective, participants in the aforementioned study were heat acclimated (25), so the effect of EIMD on exercise heat strain in non–heat-acclimated individuals in whom EHI is more prevalent (2) remains unknown.

The aim of this study was to investigate the influence of EIMD upon heat strain during subsequent exercise in the heat. To this end, we had non–heat-acclimated participants perform muscle-damaging exercise using a downhill running model (treadmill running on a −10% gradient) and then assessed heat strain during two subsequent exercise heat stress running bouts. The first exercise heat stress bout was performed 30 min post-EIMD to coincide with the early inflammatory phase (14) and expected increases in circulating pyrogen (e.g., IL-6). The second exercise heat stress bout was performed 24 h post-EIMD to coincide with the delayed muscle inflammatory response, when circulating creatine kinase (CK) values peak after downhill running (14) and when poorer economy might be expected to alter heat strain. The EIMD responses to the two exercise heat stress bouts were compared with an energy-expenditure equivalent control trial (treadmill running on a +1% gradient). We hypothesized that EIMD would increase core rectal temperature (Tre) during subsequent exercise heat stress compared with control and that the increase in Tre would be associated with increases in circulating pyrogen 30 min post-EIMD.

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METHODS

Participants

Thirteen healthy, active males volunteered to participate in the study and provided fully informed written consent. The study received local ethical approval and was conducted with the standards required by the Declaration of Helsinki. Participant characteristics were as follows (mean ± SD): age, 20 ± 2 yr; nude body mass (NBM), 70.5 ± 7.5 kg; height, 176 ± 5 cm; body mass index, 22.8 ± 2.0 kg·m−2; body surface area, 1.86 ± 0.11 m2; and maximal oxygen uptake (V˙O2max), 60 ± 5 mL·kg−1·min−1. All participants were non–heat acclimated nor accustomed to downhill running or regular eccentric exercise. Participants were nonsmokers and free from any known immune, cardiovascular, or metabolic diseases and not taking any medication (e.g., anti-inflammatories). Participants were asked to refrain from exercise 72 h before and from alcohol and caffeine 24 h before all exercise bouts. All data were collected between February and December 2011.

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Study Design

A counterbalanced experimental design in which the order of presentation of trials was randomized was used to test the hypothesis that previous muscle damage would increase rectal core temperature (Tre) during subsequent exercise heat stress. To assess this, participants completed exercise heat stress tests, 30 min (HS1) and 24 h (HS2) after both muscle-damaging exercise (EIMD: running downhill on −10% gradient) and energy-expenditure equivalent exercise (CON: running at +1% gradient). The two trials were separated by 14 d, and an overview of the study design is depicted in Figure 1.

FIGURE 1

FIGURE 1

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Fitness and familiarization

Participant’s V˙O2max was determined by a continuous maximal incremental exercise test performed on a motorized treadmill (HP Cosmos Mercury 4.0, Nussdorf-Traunstein, Germany) to volitional exhaustion. Expired gas was analyzed by an online breath-by-breath system (Cortex Metalyser 3B; Biophysik, Leipzig, Germany). From this, the treadmill running speed, which elicited 65% V˙O2max running at +1% gradient, was calculated by interpolation of the running speed–V˙O2 relationship. This running speed was subsequently verified and used as the running speed for the treatment on CON and for both heat stress tests on both trials. Participants were also asked to run downhill on a −10% gradient with expired gas analyzed continuously, with the running speed adjusted accordingly until 65% V˙O2max had been verified. This running speed was used for the treatment phase to elicit muscle damage on the EIMD trial. Participants were also familiarized with all instrumentation and procedures used in the experimental trials. They were also given diet diaries to record all food consumed during the 24 h before and during the first experimental trial and instructed to replicate this before and during the second trial.

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Experimental Trials

On the day of the experimental trial, participants arrived at the laboratory (20°C ambient temperature and 40% relative humidity [RH]) at 07:10 h fasted. Participants were provided fluids to consume (40 mL·kg−1 NBM·d−1) in the previous 24 h period to ensure they began exercise euhydrated, and this was verified by assessing urine specific gravity upon arrival (Atago Uricon-Ne refractometer; NSG Precision Cells, Farmingdale, NY). Participants were then weighed nude (NBM) on a digital platform scale accurate to the nearest 50 g (Model 705; Seca, Hamburg, Germany). On the basis of this body mass, participants were then provided with a small breakfast consisting of a cereal bar equivalent to 8.4 kJ·kg−1 NBM and water (5 mL·kg−1 NBM). At 08:15 h, baseline NBM was measured, and a rested blood sample was taken before the participant fitted a rectal thermistor probe and an HR monitor (Polar Electro, Kempele, Finland). The participant also rated their perceived muscle soreness at this point.

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Exercise Trial Treatment

The exercise trial treatment (EIMD or CON) started at 08:30 h, with participants wearing standardized clothing, that is, running shorts, socks, and shoes. Participants ran for 60 min at the predetermined speed that reflected 65% V˙O2max on either +1% gradient (CON) or −10% gradient (EIMD). Rectal core temperature (Tre) and HR were measured every 10 min, and 60-s expired gas samples were collected by Douglas bag method at 20 and 40 min of exercise and analyzed for V˙O2. Water (2 mL·kg−1 NBM) was provided every 15 min throughout treatment.

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Exercise Heat Stress 1

Immediately after treatment, participants rested for 30 min during which skin thermistors were applied. A standardized amount of water (2.5 mL·kg−1 NBM) was also provided during this period. Pre heat stress 1 (pre-HS1) NBM was assessed, and a blood sample was collected just before the participant entered the environmental chamber (Delta Environmental Systems, Chester, UK), which was maintained at a dry bulb temperature of 33°C, 50% RH, and 0.2 m·s−1 face-on wind velocity. Immediately upon entering the chamber, a ventilated capsule was attached to the forearm (for local sweating rate), and participants then began exercise heat stress (HS1) by running without fluids, on a motorized treadmill at +1% gradient for 40 min at the predetermined set running speed that reflected 65% V˙O2max. Throughout HS1, measurements taken were as follows: local forearm sweating rate, HR, Tre, skin temperature (Tsk), RPE (Borg 6–20 scale [3]), thermal sensation (McGinnis 0–13 point [22]), and 60-s expired gas samples by Douglas bag method V˙O2). Immediately after HS1, participants were removed from the chamber, seated, and a blood sample was drawn (post-HS1). Post-HS1 NBM (after towel drying) was also assessed at this time. Fluids were provided to replace sweat losses encountered during HS1, and participants were provided with a standardized meal and fluids to consume until they returned to the laboratory the following morning for the second heat stress test (HS2). Participants refrained from any exercise or the consumption of caffeine or alcohol in the intervening period between the two HS bouts.

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Exercise Heat Stress 2

HS2 was performed 24 h after the beginning of HS1. Participants reported to the laboratory and were provided with a standardized breakfast and fluids identical to the previous day. Participants rated their perceived muscle soreness just before HS2. For HS2, participants ran in the same environmental conditions and running speed as that during HS1. Before (pre-HS2) and after (post-HS2) exercise heat stress blood samples were drawn, and NBM was also assessed. All measures collected during HS2 were identical to HS1. The participant left the laboratory and returned 14 d later to complete the remaining trial.

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Measurements and Instrumentation

Body temperatures

Tre was measured using a flexible, sterile, disposable thermistor (Henleys Medical Supplies Ltd., Herts, UK) inserted 12 cm beyond the anal sphincter, with temperature recorded using a data logger (YSI model 4000A; YSI, Dayton, OH). Participants used the same thermistor in both trials. Tsk was measured at four sites on the left side of the body (on the chest at a point midway between the acromion process and the nipple, the anterior midbicep, the anterior midthigh, and the lateral calf) using insulated thermistors (Grant EUS-U, Cambridge, UK) fixed to the skin using surgical tape. Temperature data were registered using a portable data logger (Grant SQ2020, Cambridge, UK). Mean Tsk was calculated using a four-site–weighted equation (33). Because of individual skin thermistors becoming detached during HS in three participants, Tsk mean data are presented for those with a complete data set (n = 10).

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Sweating responses

Whole-body sweating rate was estimated from NBM losses during HS1 and HS2. Local forearm sweating rate was measured by dew point hygrometry. Anhydrous compressed nitrogen was passed through a 5-cm2 capsule placed on the lower arm ventral surface (halfway between the antecubital fossa and carpus) and connected to a hygrometry system (DS2000; Alpha Moisture Systems, UK). Local forearm sweating rate was calculated using the difference in water content between effluent and influent air and the flow rate (1 L·min−1) and normalized for the skin surface area under the capsule (expressed in milligrams per square centimeter per minute). Sweating threshold and sensitivity were calculated by plotting individual relationships between local forearm sweating rate and Tre values. A simple linear regression equation for the initial 4 min of exercise was calculated, with the threshold Tre for active thermoregulatory sweating defined as the Tre at which local forearm sweating rate = 0.06 mg·cm−2·min−1 (8). Sweating sensitivity was calculated as the slope of the linear regression line for both (a) the exercise transient phase (when the rapid increase in sweating rate occurred during the initial 4 min of exercise) and (b) the plateau sweating phase (when sweating rate plateaued from 6 to 40 min of exercise).

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Rate of metabolic energy expenditure ()

Oxygen consumption (V˙O2) was calculated for 60 s expired air samples collected into a Douglas bag and analyzed for O2 and CO2 concentrations (Servomex, Crowborough, UK) and volume (Harvard Apparatus, Edenbridge, UK). was calculated using V˙O2 (L·min−1) and RER in the following equation (28):

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Perceived leg muscle soreness

Perceived leg muscle soreness was self-rated using two scales. First, participants rated leg muscle soreness using a 100-mm visual analog scale anchored on the left with the phrase “My leg muscles don’t feel sore at all” and anchored on the right with the phrase “My leg muscles feel so sore I don’t want to move them.” Participants gave their rating while performing a wall sit with their legs bent 90°. Participants also rated their leg muscle soreness using a seven-point validated Likert scale (40) while walking up and down the laboratory.

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Blood collection, handling, and analysis

Whole blood samples were collected, without venostasis, by venepuncture from an antecubital vein and collected into one K2EDTA and one lithium heparin vacutainer tube (BD, Oxford, UK). Hematocrit (capillary method) using a microhematocrit reader (Hawksley & Sons Ltd., Lancing, UK) and hemoglobin concentration using a photometer (Hemocue, Sheffield, UK) were both analyzed immediately on whole blood in triplicate with plasma volume change calculated (17). The remaining whole blood was spun in a refrigerated centrifuged at 1500g for 10 min, with the plasma aspirated, aliquoted into Eppendorf tubes, and frozen at −80°C for later analysis. CK activity pretreatment and 24 h posttreatment was assessed as an indirect measure of muscle damage. Plasma CK activity was measured in duplicate, on lithium heparin-treated plasma using an enzyme reaction kit (EnzyChrom™ CK assay kit; BioAssay Systems, Hayward, CA). The intra-assay coefficient of variation for CK was 3.8%. Plasma IL-6 concentrations were determined at baseline and before and after HS1 and HS2 on EDTA-derived plasma in duplicate using a commercially available high sensitivity ELISA (Quantikine® HS IL-6, HS600B; R&D Systems Europe, Abingdon, UK). Intra-assay coefficient of variation for plasma IL-6 concentration was 5.3%. For all biochemical analyses, the participant’s samples were always assayed on the same plate.

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Statistical Analysis

A sample size calculation was performed (G*Power, 3.1.2) using mean and SD core temperature data from Montain et al. (25). For a two-tailed test with alpha level set at 0.05, and power set at 0.8, recruiting 12 participants was deemed appropriate to detect a significant difference in core rectal temperature between the conditions during subsequent exercise in the heat. All data were checked for normality and sphericity and analyzed using either paired t-tests or fully repeated-measures ANOVA with the Greenhouse–Geisser correction applied to the degrees of freedom if necessary. All F values reported are for the time – trial interaction unless otherwise stated. Tukey’s HSD or Bonferroni-adjusted paired t-test post hoc procedures were used to determine within-subject differences where appropriate. To assess the contribution of acute circulating inflammation (IL-6) after muscle damage on altered heat strain during subsequent exercise heat stress, Pearson correlations were performed by correlating the pre-HS IL-6 concentration with the final Tre attained during HS. All data were analyzed using SPSS version 14 software (IBM, NY). Statistical significance was accepted as P < 0.05.

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RESULTS

Treatment Responses

Both treatments (−10% [EIMD] and +1% gradient running [CON]) were conducted at the same exercise intensity with no between-trial differences in (EIMD = 939 ± 111, CON = 941 ± 106 W, P = 0.90) or RER (EIMD = 0.92 ± 0.05, CON = 0.94 ± 0.05, P = 0.25). Despite being conducted at the same exercise intensity, ΔTre was greater during 60 min −10% downhill running (EIMD = 1.88°C ± 0.33°C) than 60 min +1% gradient running (CON = 1.25°C ± 0.27°C; P < 0.001). However, 30 min posttreatment and just before HS1, Tre was not different between trials (P = 0.52). Sixty minutes of downhill running was successful in inflicting muscle damage because indirect markers of muscle damage, assessed by plasma CK and perceived muscle soreness (VAS and Likert scale), were all significantly greater on EIMD than CON 24 h posttreatment (P < 0.001, Table 1). Furthermore, all participants on EIMD had increases in plasma CK and perceived muscle soreness (VAS and Likert scale), and these responses were greater on EIMD compared with CON 24 h posttreatment for all participants. There were no baseline differences for any of these variables.

TABLE 1

TABLE 1

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Exercise Heat Stress Responses

Rectal core and skin temperature

Mean ΔTre, Tre, and Tsk responses to HS1 and HS2 are presented in Figure 2. Tre demonstrated an interaction during both HS1 (F = 8.8, P < 0.01) and HS2 (F = 6.3, P < 0.01). There was no significant difference in starting Tre between trials before HS1 or HS2. The ΔTre during HS1 was greater after EIMD than CON (P < 0.01; Fig. 2A). During HS1, Tre was significantly higher after EIMD than CON 16 min onward, resulting in a higher final Tre after 40 min of the same exercise heat stress (EIMD = 39.53°C ± 0.42°C, CON = 39.01°C ± 0.38°C, P < 0.01; Fig. 2C). Furthermore, five participants showed evidence of mild hyperthermia with a Tre > 39.5°C on EIMD compared with only one participant on CON. During HS2, ΔTre was also significantly greater after EIMD than CON (P < 0.05; Fig. 2B). Although post hoc testing failed to show any significant differences in actual Tre between trials throughout HS2, there was a trend for a 0.13°C higher final Tre on EIMD than CON during HS2 (P = 0.08; Fig. 2D). Mean Tsk was not altered by previous muscle-damaging exercise during HS1 (F = 2.1, P = 0.17; Fig. 2E) or HS2 (F = 0.44, P = 0.56; Fig. 2F).

FIGURE 2

FIGURE 2

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Sweating rate and plasma volume change

Whole body sweating rate was not different between trials during HS1 (EIMD = 23.1 ± 8.2, CON = 23.2 ± 5.0 mL·min−1, P = 0.98) or HS2 (EIMD = 21.4 ± 9.0, CON = 22.6 ± 5.0 mL·min−1, P = 0.62). There was a small interaction for local forearm sweating rate during HS1 (F = 2.9, P < 0.05; Fig. 3A), with sweating rate only higher after 2 min of exercise on EIMD than CON (P < 0.05). Despite the threshold temperature for initiation of sweating visually appearing to occur at a higher Tre on EIMD than CON during HS1 (Fig. 3C), this was not significant (P = 0.36). There was no difference in sweating sensitivity between trials during the initial transient exercise phase (P = 0.50) nor later during exercise in HS1 (6–40 min, P = 0.19). Throughout HS2, there was no effect of previous muscle damage on local forearm sweating rate (F = 2.2, P = 0.12; Fig. 3B) nor sweating threshold temperature (P = 0.95), sweating sensitivity during the initial transient phase of exercise (P = 0.69), or sweating sensitivity during the plateau sweating phase from 6 to 40 min of exercise (P = 0.17; Fig. 3D). There was no effect of muscle damage on plasma volume change during HS1 and HS2 (no interaction, F = 1.7, P = 0.15, or main effect of trial, F = 0.1, P = 0.75).

FIGURE 3

FIGURE 3

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Rate of metabolic energy expenditure, RER, and HR

Mean was significantly higher after EIMD than CON throughout both HS1 and HS2 (HS1: EIMD = 1040 ± 115 W, CON = 970 ± 102 W, P < 0.001; HS2: EIMD = 986 ± 131 W, CON = 920 ± 113 W, P < 0.001). These metabolic rates equated to 71% ± 6% and 66% ± 6% V˙O2max for EIMD and CON, respectively, during HS1, and 67% ± 6% and 62% ± 6% V˙O2max for EIMD and CON, respectively, during HS2. There was no difference in mean RER between EIMD and CON throughout either HS1 (EIMD = 0.94 ± 0.05, CON = 0.92 ± 0.04, P = 0.35) or HS2 (EIMD = 0.94 ± 0.03, CON = 0.96 ± 0.07, P = 0.19). Mean HR throughout both HS1 and HS2 was significantly greater on EIMD than CON (HS1: EIMD = 177 ± 12 beats·min−1, CON = 168 ± 14 beats·min−1, P < 0.01; HS2: EIMD = 164 ± 12 beats·min−1, CON = 159 ± 11 beats·min−1, P < 0.05).

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Thermal sensation and RPE

Thermal sensation and RPE data are presented in Figure 4. Participants rated their thermal sensation significantly hotter on EIMD than CON from 25 min onward throughout HS1 (F = 5.7, P < 0.01; Fig. 4A). Throughout HS2, there was a trend for a higher thermal sensation during EIMD than CON (main effect of trial, F = 4.4, P = 0.06; Fig. 4B). Participant’s RPE was higher from 25 min onward on EIMD during HS1 (F = 4.1, P < 0.05, main effect of trial F = 7.4, P < 0.01; Fig. 4C). Participants RPE was considerably higher on EIMD than CON 24 h posttreatment throughout HS2 (main effect of trial, F = 11.4, P < 0.01; Fig. 4D).

FIGURE 4

FIGURE 4

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Plasma IL-6

We measured plasma IL-6 concentration as a circulating marker of inflammation. Plasma IL-6 concentration was not different between trials at baseline but responded differently to the treatment and heat stress tests (F = 18.1, P < 0.001; Fig. 5). Thirty minutes after treatment and immediately before HS1, plasma IL-6 concentration was significantly elevated above baseline on EIMD (P < 0.001) and CON (P < 0.01). Importantly, participants began HS1 on EIMD with a significantly higher plasma IL-6 concentration than CON (P < 0.01). In addition, the plasma IL-6 exercise response to HS1 was significantly greater on EIMD versus CON (P < 0.01). The acute circulating inflammatory response after treatment, measured as the pre-HS1 plasma IL-6 concentration, correlated with the final Tre attained after HS1 (r = 0.67, P < 0.01). On day 2, immediately pre-HS2, plasma IL-6 concentrations on both trials had returned to baseline values with no difference between trials. As such, the preceding IL-6 response was not strongly associated with final Tre during HS2 (r = −0.33, P = 0.10). Plasma IL-6 concentration increased after HS2 on both EIMD and CON (P < 0.01) with no between-trial differences.

FIGURE 5

FIGURE 5

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DISCUSSION

In line with our hypothesis, here we have shown in non–heat-acclimated males that ΔTre is increased during exercise heat stress performed 30 min after moderate muscle-damaging exercise timed to coincide with the early inflammatory phase. This resulted in a ∼0.5°C greater final Tre during HS1 in muscle damaged individuals (final Tre ∼39.5°C) after just 40 min of moderate exercise heat stress, which under hot environmental conditions could conceivably accelerate the progression of the individual toward EHI. We have also shown that the preceding EIMD-evoked increase in plasma IL-6 concentration was associated (r = 0.67) with increased heat strain during HS1 conducted 30 min after EIMD. When exercise heat stress was timed to coincide with the delayed muscle inflammatory phase 24 h after moderate muscle-damaging exercise, we also observed a significant, albeit small, increase in ΔTre. These results have practical relevance, particularly for non–heat-acclimated athletes and soldiers who undertake repeated, and/or prolonged heavy training bouts, with an eccentric component, in hot environmental conditions. Strategies that can reduce EIMD-associated inflammation may alleviate the risk of EHI.

Downhill running is often used in studies to evoke muscle damage (6,30,31), and the aim of the model used here was to elicit moderate, realistic muscle damage that would not impair the participants ability to complete the subsequent exercise heat stress bouts. All participants were able to complete the HS bouts, and the degree of muscle damage was equivalent to experiencing “a light pain when walking” (40). In addition, EIMD resulted in greater increases in plasma CK concentration than CON. Although we acknowledge that we did not assess muscle strength as an indicator of muscle damage and the limitations of plasma CK and delayed onset of muscle soreness as markers of EIMD (30), the mode of EIMD (downhill running) and severity of soreness experienced may reflect that encountered by soldiers and athletes undergoing unaccustomed exercise. Although not a central focus of the present study, an important finding that should not be overlooked in the context of EHI risk is the greater increase in Tre (+0.63°C) during the EIMD treatment in thermoneutral conditions. This occurred despite exercise intensity being carefully matched in CON and EIMD and is likely explained by altered muscle fiber recruitment and efficiency during eccentric exercise (1). With our primary aim in mind, it is noteworthy that Tre was not significantly different between trials before commencement of HS1, 30 min later, or HS2, 24 h later.

To the best of our knowledge, the only published study that has investigated heat strain during exercise heat stress after muscle injury showed a 0.2°C–0.3°C greater core body temperature than control at 2 h and 7 h, but no effect 26 h after injury (25). In line with our two phase approach, here we observed a 0.35°C greater increase in Tre during exercise heat stress conducted 30 min post-EIMD timed to coincide with the early inflammatory phase, where participants showed evidence of mild hyperthermia (mean final Tre: EIMD = 39.5°C, CON = 39.0°C). The 0.17°C greater increase in Tre during exercise heat stress conducted 24 h post-EIMD indicates a lesser effect of the delayed muscle inflammatory phase on exercise heat strain. These observations occurred without any significant differences between trials in thermoeffector response measures (e.g., skin temperature, whole body and local sweating rate, and sweating sensitivity) or hydration (plasma volume change). We acknowledge the limitations with measuring local sweating rate at only one site and using Tre to calculate sweating sensitivity as opposed to esophageal temperature, which responds more quickly during exercise-induced hyperthermia (21). We felt that these were necessary compromises because of the practical constraints of the running mode of exercise and for participant comfort. Eccentric exercise has been shown to inhibit glycogen resynthesis (16,29), thus one might hypothesize that altered substrate availability may have affected metabolism and contributed to increased heat strain, particularly during HS2. However, this is unlikely because we did not observe any differences between trials in RER during HS1 or HS2. On the basis of previous findings (25), one might also anticipate a significant involvement of poorer economy in the increased heat strain after EIMD, possibly due to modified gait, greater motor unit recruitment, and/or muscle weakness due to the muscle-damaging protocol (25). In support of this premise, , HR, and RPE were greater during HS1 and HS2 after EIMD. Muscle-damaging exercise in humans has been shown to reduce economy, with steady-state exercise V˙O2 elevated 3%–7% in the 3 d after downhill running (6,12). Furthermore, rodent models have shown that damaged muscle fibers also demonstrate decreased contraction economy (42).

We measured circulating IL-6 concentration as a marker of acute inflammation and hypothesized that EIMD-evoked increases in circulating IL-6 would be associated with increased heat strain during subsequent exercise heat stress 30 min after muscle-damaging exercise (HS1). As anticipated, EIMD brought about a significantly greater circulating IL-6 response than CON before HS1, although it is noteworthy that the circulating level of IL-6 after EIMD was relatively modest compared with the level typically observed after more prolonged, metabolically demanding endurance exercise (27). Nevertheless, we observed a moderate correlation between the previous circulating IL-6 concentration and the final Tre during HS1 (r = 0.67). It is important to stress the sequential nature of this relationship, that is, it was the preceding, albeit modest, early inflammatory response that was associated with subsequent increases in Tre during exercise heat stress. Furthermore, these associations were not evident during HS2 when pre-HS2 IL-6 concentrations had returned to baseline values, with no difference between trials. Because IL-6 is a known pyrogen (18), it is plausible that acute increases in circulating IL-6 after muscle damage may act upon the cycloxygenase 2–mediated PGE2 pathway, resulting in an increase in the thermoregulatory set point (5,37) and heat strain during exercise heat stress. However, we acknowledge the relatively modest augmentation in the circulating IL-6 response after EIMD and that the concept of a thermoregulatory set point remains controversial (36). Future studies should investigate the putative contribution of pyrogenic pathways after muscle damage upon exercise heat strain. Because the exercise intensities on the two treatments were tightly matched, with no differences in RER, it is unlikely that altered metabolic demands or fuel utilization during treatment could account for the greater plasma IL-6 after EIMD (20,30). Whether the greater circulating IL-6 response after EIMD originates from muscle cells, leukocytes, or other cells remains a topic of debate (7,25,30).

Soldiers and athletes undergoing heavy training are frequently expected to perform repeated bouts of arduous physical activity on the same day, often in hot environments that might predispose them to EHI (2). Irrespective of the underlying mechanisms, based on the findings of the current study, it is conceivable that the non–heat-acclimated soldier or athlete may experience greater heat strain during a subsequent exercise heat stress bout performed shortly after, and to a much lesser extent, the following day after unaccustomed muscle-damaging exercise. We also observed a greater increase in Tre during the −10% gradient downhill running treatment than the energy-expenditure matched +1% gradient running exercise. Taking this into account, individuals undertaking a prolonged bout of exercise in the heat that includes an eccentric component, such as running or walking across mountainous terrain, might also experience greater heat strain. Given the increase in thermal sensation during HS1 and increase in RPE during HS1 and HS2 after EIMD, the effects of EIMD may be somewhat self-limiting; that is, we anticipate that in many cases, the exercising individual would lower their exercise intensity while exercising in the heat after EIMD. Nevertheless, it is a common observation in military and athletic scenarios that very motivated and highly experienced individuals choose to ignore some of the normal behavioral thermoregulation cues (38) so they too could be at increased risk of EHI as a consequence of EIMD. Likewise, we might expect EIMD-associated increased heat strain during exercise in the heat when the exercise intensity is externally regulated, for example, during group exercises in military scenarios. EIMD has not been included as a risk factor for EHI in recent reports (2,11), but our data indicate that EIMD should be given due consideration as a risk factor for EHI, particularly for exercise in hot environments. Because we have shown an association, albeit moderate, between previous acute circulating inflammation and subsequent exercise heat strain, a logical line of enquiry is to identify strategies that can reduce inflammation, which in turn may lessen the rise in Tre and decrease the risk of EHI during exercise heat stress. It needs to be established, for example, whether the well-known repeated bout effect for muscle-damaging exercise (15) or a period of heat acclimatization provides protection from the herein demonstrated increase in heat strain during exercise heat stress after EIMD. Nonsteroidal anti-inflammatory drugs (e.g., Ibuprofen) are an unsuitable candidate because nonsteroidal anti-inflammatory drugs augment the plasma IL-6 response in ultramarathon runners (26) and increase gastrointestinal permeability, which in turn might increase the risk of EHI through the immune sequelea that results from gastrointestinal endotoxin leakage (23,24). Whether strategies that dampen inflammation also curtail some of the important cell signaling and associated physiological adaptations with training remains a moot point. It is quite conceivable that strategies to decrease inflammation may decrease the risk of EHI for athletes and soldiers performing in hot environments in the short term but paradoxically decrease some of the training adaptations in the long term (e.g., anti-inflammatory supplementation using antioxidants [32,35]); clearly, more evidence is required before we will know whether this is an ill-conceived concept.

In conclusion, these data show that a bout of EIMD, brought about by downhill running, increases heat strain during subsequent endurance exercise in the heat conducted 30 min after and, to a much lesser extent, 24 h after muscle damage. EIMD-evoked increases in circulating pyrogen IL-6 were associated with increased heat strain during exercise heat stress conducted 30 min after EIMD. These results have practical relevance, particularly for non–heat-acclimated athletes and soldiers undertaking either multiple, or prolonged bouts of heavy exercise with an eccentric component in the heat.

The authors thank the following people for their valuable assistance with data collection: Lindsey Jankowski, Megan Butterworth, Ben Terzza, Dominique Mauger, Tom Riddle, and Daniel Kashi. They are also indebted to the participants for their time and cooperation. This study received no external funding.

None of the authors had a conflict of interest.

The results of the present study do not constitute endorsement by the American College of Sports Medicine.

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Keywords:

THERMOREGULATION; ECCENTRIC; HYPERTHERMIA; HEAT ILLNESS; HEAT STROKE; INFLAMMATION

© 2013 American College of Sports Medicine