Journal of Applied Physiology Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 89: 1123-1130, 2000;
8750-7587/00 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Montain, S. J.
Right arrow Articles by Sawka, M. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Montain, S. J.
Right arrow Articles by Sawka, M. N.
Vol. 89, Issue 3, 1123-1130, September 2000

Impact of muscle injury and accompanying inflammatory response on thermoregulation during exercise in the heat

Scott J. Montain, William A. Latzka, and Michael N. Sawka

Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts 01760-5007


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

This study examined whether muscle injury and the accompanying inflammatory responses alter thermoregulation during subsequent exercise-heat stress. Sixteen subjects performed 50 min of treadmill exercise (45-50% maximal O2 consumption) in a hot room (40°C, 20% relative humidity) before and at select times after eccentric upper body (UBE) and/or eccentric lower body (LBE) exercise. In experiment 1, eight subjects performed treadmill exercise before and 6, 25, and 30 h after UBE and then 6, 25, and 30 h after LBE. In experiment 2, eight subjects performed treadmill exercise before and 2, 7, and 26 h after LBE only. UBE and LBE produced marked soreness and significantly elevated creatine kinase levels (P < 0.05), but only LBE increased (P < 0.05) interleukin-6 levels. In experiment 1, core temperatures before and during exercise-heat stress were similar for control and after UBE, but some evidence for higher core temperatures was found after LBE. In experiment 2, core temperatures during exercise-heat stress were 0.2-0.3°C (P < 0.05) above control values at 2 and 7 h after LBE. The added thermal strain after LBE (P < 0.05) was associated with higher metabolic rate (r = 0.70 and 0.68 at 2 and 6-7 h, respectively) but was not related (P > 0.05) to muscle soreness (r = 0.47 at 6-7 h), plasma interleukin-6 (r = 0.35 at 6-7 h), or peak creatine kinase levels (r = 0.22). Local sweating responses (threshold core temperature and slope) were not altered by UBE or LBE. The results suggest that profuse muscle injury can increase body core temperature during exercise-heat stress and that the added heat storage cannot be attributed solely to increased heat production.

trauma; eccentric exercise; temperature regulation; heat illness; heat injuries; cytokines


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

EXERTIONAL HEAT ILLNESS is a substantial problem in military, sports, and occupational medicine. In the military, exertional heat illnesses account for 2% of clinic visits during summer basic training (11). Most exertional heat illness incidents occur during the initial weeks of physical training (1, 7, 11, 21) and predominantly afflict persons who are overweight and unfit (7, 21). For example, Gardner et al. (7) found that male recruits with a body mass index >22 kg/m2 and an initial 1.5-mile run time >12 min have an eightfold higher risk than leaner and more fit counterparts. Exertional heat illness incidents often are associated with the previous day's heat stress (11) and occur shortly after initiation of exercise (5). Furthermore, epidemiological studies reveal that 16-18% of heat stroke victims were sick on the days preceding the event (5, 21). These latter observations support the notion that persons who develop exertional heat illness may begin exercise in a compromised condition, and some event (possibly muscle injury and the inflammatory response), triggered by strenuous physical exercise, adversely affects thermoregulation and increases the risk of heat injury.

Persons performing novel exercise typically experience muscle injury and develop soreness. Accompanying the muscle damage is a local inflammatory response that includes infiltration of leukocytes (WBCs) into the damaged tissue (6, 24). Concomitant with these changes are elevated plasma and/or tissue levels of the cytokines interleukin (IL)-1beta , IL-6, and tumor necrosis factor (2, 3, 6, 16). Because these physiological responses to injury are similar to the events accompanying acute infection and infection is a known risk factor for development of exertional heat illness (5, 16), it is possible that acute muscle injury might adversely alter thermoregulation and increase the risk of exertional heat illness. No study, to our knowledge, has examined whether muscle injury and the subsequent inflammatory responses modify human thermoregulation during exercise in the heat.

It is conceivable that an initial muscle injury might also "sensitize" the body so that a second set of muscular injuries would accentuate adverse thermoregulatory responses. It has been demonstrated that immunoadjuvant exposure 3 days before introduction of endogenous pyrogen will enhance the febrile response to pyrogen exposure (22, 23). Because tissue injury can produce an acute inflammatory response and secretion of cytokines (2, 3, 6, 16), it is possible that muscle or other tissue injury (i.e., gut, endothelial) produced by prior exercise could serve as the priming mechanism to sensitize the brain receptor sites to subsequent cytokine exposure and alter the thermoregulatory responses to exercise-heat stress.

The purpose of this study was to determine whether muscle injury and accompanying inflammatory response adversely alter thermoregulation during subsequent exercise-heat stress. We hypothesized that muscle injury and the accompanying inflammatory response would adversely impact on thermoregulation in the heat, as evidenced by increased heat storage and reduced sweating responses. In addition, we hypothesized that a relationship would be found between the magnitude of the inflammation response (as measured by plasma IL-6 response) and the adverse thermoregulatory responses.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Subjects

Sixteen subjects participated in the study: eight (7 men and 1 woman) in experiment 1 and eight (5 men and 3 women) in experiment 2. Age, weight, height, and maximum O2 consumption (VO2 max) were (mean ± SE, with range in parentheses) 21 ± 2 (18-32) yr, 76.1 ± 3.2 (65.4-90.6) kg, 174 ± 1 (170) cm, and 52.1 ± 2.3 (36.8-56.1) ml · kg-1 · min-1 for experiment 1 and 20 ± 1 (18-29) yr, 71.4 ± 4.4 (54.2-89.4) kg, 170 ± 3 () cm, and 54.9 ± 2 (45.5-63.4) ml · kg-1 min-1 for experiment 2, respectively. No subject had prior history of heat intolerance or prior history of chronic knee or elbow injuries. No subject had been lifting weights or performing resistive exercise during 2 mo preceding experimental testing. Volunteers were informed verbally and in writing of the objectives and procedures of the study. They were allowed to withdraw at any time. This investigation was approved by appropriate Institutional Review Committees, and all volunteers provided informed consent.

Experimental Design

The experimental approach was to examine the thermoregulatory responses to a standardized exercise (treadmill)-heat stress test before and at selected times after induction of muscle injury. Two separate experiments were conducted. Experiment 1 initially examined whether injury to the upper body muscles increased the thermoregulatory strain of the treadmill heat stress test. Next, muscles of the lower body were injured, and the heat stress test was repeated to examine whether the initial inflammation response might predispose persons with subsequent muscle injury to adverse thermoregulatory effects and/or whether the addition of more injury increased the thermoregulatory strain of exercise. Experiment 2 was performed to better characterize the thermoregulatory responses during the initial hours after induction of muscle injury. Lower body eccentric exercise (LBE) was used to induce muscle injury on the basis of the observation that injury to this body region significantly increased plasma IL-6 levels during the recovery period.

Heat acclimation. To ensure stable thermal and cardiovascular responses to the treadmill heat stress test, the subjects performed a heat acclimation program before experimental testing. Treadmill exercise eliciting 45-50% VO2 max was performed in a hot-dry climate (40°C, 20% relative humidity) on 6 of 7 consecutive days. The heat acclimation protocol consisted of two 50-min exercise bouts separated by 10 min of rest. Rectal temperature and heart rate were measured throughout exercise. Rectal temperature and heart rate responses were similar over the final 3 days of the heat acclimation protocol. Subjects were allowed to drink ad libitum during the acclimation protocol.

Experiment 1. After the heat acclimation protocol, the volunteers performed 50 min of treadmill walking in the morning and afternoon on 2 consecutive days (days 9 and 10) to establish baseline body temperatures and local sweating and heart rate responses to the exercise-heat stress test (40°C, 20% relative humidity). The two baseline morning heat stress tests (0900) and the two afternoon heat stress tests (1400) were averaged for morning control and afternoon control heat stress test responses, respectively. The exercise intensity and climatic conditions were kept the same as during heat acclimation. Rehydration and recovery activities were standardized before the morning tests and between the morning and afternoon tests to minimize differences between tests.

On the following morning, eccentric exercise (see Muscle injury) was performed to produce diffuse muscle injury to the upper body muscles (UBE). On that afternoon (1400, ~6 h after the eccentric exercise), volunteers repeated the heat stress test. On the following morning (0900, ~25 h after eccentric exercise) and afternoon (1400, ~30 h after eccentric exercise), the heat stress test was repeated. The time of all morning and afternoon heat stress tests was kept constant to control for circadian variation and to enable comparison with the control tests. At 48 h after the initial eccentric exercise bout, eccentric exercise was performed to produce injury to the lower leg muscles (LBE). At 6, 25, and 30 h after this eccentric exercise bout, the heat stress tests were attempted to assess whether additional muscle injury increased the thermal strain of exercise. The time line for the experiment is graphically presented in Fig. 1.


View larger version (25K):
[in this window]
[in a new window]
  		Fig. 1.   Time line for experimental procedures for experiments 1 and 2. VO2, maximal O2 uptake testing and determination of treadmill settings to elicit 50% of maximal VO2; HA, heat acclimation, 100 min of exercise/day; HST, heat stress test, 50 min of exercise; UBE and LBE, upper and lower body eccentric exercise, respectively.

Experiment 2. The design of experiment 2 was similar to that of experiment 1: 6 days of heat acclimation preceded experimental testing, 2 days of baseline measurements were made, and the heat stress test protocols were identical. However, for experiment 2, eccentric exercise was performed only on the upper leg muscles and the posteccentric exercise trials were performed 2, 7, and 26 h after LBE. These experimental changes were made after the IL-6 responses in experiment 1 as well as the accompanying thermoregulatory responses were observed and allowed examination of physiological responses during the initial hours (2 h) after eccentric exercise.

Muscle injury. An eccentric exercise model was employed that has been shown to induce muscle damage and soreness (4, 15). Injury was induced to the chest, shoulders, upper back, upper arm, and upper leg skeletal muscle groups. Subjects performed the eccentric portion of seven standard strength-training tasks: the bench press, seated row, military press, pull down, arm curl, 45° leg press, and leg curl. Technicians performed the concentric portion of each repetition for the subject (i.e., return the load to the "start" position). The mass was set at each subject's movement-specific one repetition maximum. Subjects performed 4 sets of 10 repetitions of each exercise, with the eccentric phase of each repetition lasting 4 s and the return phase (performed by the technicians) lasting 1 s. Approximately 1 min of rest was provided between sets. Movement speed was controlled with a sound-producing feedback system. In the event that subjects were not able to support the load throughout the range of motion, the technicians provided support to maintain the desired rate of movement.

The maximal lifting capacity for the bench press, seated row, military press, pull down, arm curl, 45° leg press, and leg curl exercises was measured by lifting increasingly heavier loads until the maximum ability was achieved. During one-repetition-maximum testing, the subjects performed only the concentric movements to avoid any eccentric exercise before the soreness-inducing eccentric exercise sessions. Subjects were verbally encouraged to give their best effort. A minimum of 30 s of rest separated each lift.

Procedures

VO2 max was measured using a continuous-effort incremental-intensity treadmill protocol (20). O2 uptake and CO2 production were measured by indirect calorimetry. Subjects were asked to walk at a combination of treadmill speed and grades to determine a combination that elicited 45-50% of their VO2 max. The treadmill grade and speed that closest approximated 45-50% of their VO2 max was used for heat acclimation and the heat stress tests.

Rectal temperature was measured by a thermistor inserted ~8 cm past the anal sphincter. Esophageal temperature was measured by a thermocouple inserted through the nose and placed at approximately heart level (approximately one-fourth of the subject's standing height) (19). Skin temperatures were measured from thermocouples placed on the torso and limbs (18). Sweating rate of the upper arm was measured with a ventilated capsule containing a dew-point sensor (9). The flow rate was set at 1.16 l/min. Whole body sweating rate was measured from body mass measured to the nearest ±20 g before and after exercise. Heart rate was measured using a heart rate monitor (Polar Electro, Kempele, Finland) and recorded every 10 min. Body temperatures and dew-point temperatures were collected at 30-s intervals. O2 uptake and CO2 production were determined from 90-s Douglas bag collections at 25 min of exercise.

Mean skin temperature was calculated as follows: 0.3(Tchest + Tarm) + 0.2(Tthigh + Tcalf), where Tchest, Tarm, Tthigh, and Tcalf are chest, arm, thigh, and calf temperatures, respectively. Mean body temperature was calculated using a ratio of 9:1 for core and mean skin temperatures, respectively. Sweating threshold was defined as the esophageal temperature at the onset of progressive sweating increases accompanying exercise. Sweating sensitivity was determined from linear regression analysis of the sweating response during the 3- to 20-min period of exercise. Heat storage was calculated as follows: S = [(mb · cb)/AD] · (dTb/dt), where mb is body mass (kg), cb is the specific heat constant (0.965 W · h · °C-1 · kg-1), AD is DuBois body surface area (m2), dTb is change in mean body temperature during 50 min of exercise (°C), and dt is exposure time (0.833 h). Energy expenditure was calculated from the respiratory exchange ratio and O2 uptake measurements.

No fluids were provided during the heat stress test. Body mass (men, shorts only; women, shorts and sports bra) was measured before and after exercise to determine whole body sweat loss. Blood samples were obtained from a catheter inserted in a forearm vein of subjects in the seated position before exercise and at 30 min of exercise for measurement of osmolality, creatine kinase, IL-6, and complete blood count. At 48 h after LBE, an additional blood sample was drawn to measure plasma creatine kinase concentration.

At each blood draw, 7 ml of blood were drawn into chilled EDTA tubes. An aliquot was used to perform a complete blood count (Coulter Onyx, Coulter, Miami, FL), the remaining volume was centrifuged, and plasma was stored at -70°C until analysis. Creatine kinase concentration was measured by enzymatic kit (Sigma Chemical, St. Louis, MO). IL-6 was measured by ELISA (R & D Systems, Stillwater, MN). An additional 5-ml blood sample was drawn at rest into a blank tube, allowed to clot for 20 min, and then assayed for serum osmolality (Multi Osmette, Precision Systems, Natick, MA). During experiment 1, insufficient blood was aliquoted to measure WBC responses.

Subjective soreness of the pectoralis, latissimus dorsi, biceps, quadriceps, and hamstring muscles was assessed using a 127-mm continuous line, one end representing no soreness and the other representing extreme soreness. Point tenderness was scored using a four-point scale.

Statistical Analysis

The thermoregulatory responses to treadmill exercise were compared using repeated-measures ANOVA. When P < 0.05 was obtained, mean differences were identified using Tukey's honestly significant difference test. Baseline thermoregulatory responses were obtained by averaging the responses to the two morning and two afternoon control trials completed before the eccentric exercise. The effect of muscle injury on the variables measured was determined by comparing the posteccentric exercise trials with their respective control trial performed at the same time of day (i.e., morning trials and afternoon trials were compared separately). Values are means ± SE. Preexperiment power analysis suggested that eight subjects would be sufficient to detect a 0.3°C difference in core temperature at power of 0.8 and alpha  < 0.05.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Heat Acclimation

The heat acclimation procedures were successful at eliminating test-retest variability in physiological responses to the heat stress test, inasmuch as mean core temperatures and heart rates at 50 min of exercise were within 0.05°C and 3 beats/min, respectively, on the 2 baseline days preceding eccentric exercise.

Muscle Injury

During experiment 1, eccentric exercise produced muscle injury as indicated by elevated muscle enzymes and subjective assessment. Creatine kinase levels increased (P < 0.05) progressively after the UBE protocol (Table 1). Plasma IL-6 concentrations remained similar to baseline levels after UBE but were elevated (P < 0.05) at 6 h after LBE (Fig. 2). After UBE, subjective soreness of chest, upper back, biceps, and triceps muscles increased (P < 0.05) dramatically and averaged 104 ± 7 mm (on a 127-mm scale) at 25 h. Point tenderness of these upper body muscles averaged 2.8 ± 0.3 (4-point scale). After LBE, subjective soreness of thigh, hamstring, and gluteal muscles increased (P < 0.05) and averaged 93 ± 13 and 103 ± 13 mm at 25 and 30 h, respectively. Point tenderness of these lower body muscles averaged 2.8 ± 0.4 at 25 h.

                              
View this table:
[in this window]
[in a new window]
  		Table 1.   Plasma creatine kinase concentrations before and after UBE and LBE (experiment 1) or after LBE only (experiment 2)



View larger version (18K):
[in this window]
[in a new window]
  		Fig. 2.   Plasma interleukin-6 (IL-6) responses to experiment (Exp) 1. A: plasma IL-6 concentrations at rest and at 30 min of treadmill exercise during control trial and 6 and 30 h after UBE. B: plasma IL-6 concentrations at rest and at 30 min of treadmill exercise for control trial and 6 and 30 h after LBE. * 30-min exercise value 6 h after LBE was greater than control value, P < 0.05. Values are means ± SE for 8 subjects.

During experiment 2, LBE produced skeletal muscle injury as indicated by elevated muscle enzymes, WBC changes, and subjective assessment. Creatine kinase levels increased (P < 0.05) progressively during the 48-h period after LBE (Table 1). Plasma IL-6 was elevated (P < 0.05) at 7 h but was similar to control values 2 and 26 h after eccentric exercise (Fig. 3). Plasma WBC concentration increased (P < 0.05) by 43% and 28% at 2 and 7 h after LBE, respectively (2 h vs. control: 7.0 ± 0.4 vs. 4.9 ± 0.4 × 103 cells/µl; 7 h vs. control: 8.6 ± 0.5 vs. 6.7 ± 0.3 × 103 cells/µl) largely because of increased numbers of monocytes (2 h vs. control: 615 ± 64 vs. 340 ± 25 µl-1; 7 h vs. control: 745 ± 54 vs. 465 ± 33 µl-1) and granulocytes (2 h vs. control: 4,827 ± 299 vs. 3,332 ± 310 µl-1; 7 h vs. control: 6,044 ± 416 vs. 4,391 ± 204 µl-1). At 26 h after LBE, WBC concentration was 37% above baseline levels (6.7 ± 0.4 vs. 4.9 ± 0.4 × 103 cells/µl, P < 0.05) because of increased numbers of lymphocytes (+51%), monocytes (+58%), and granulocytes (+28%). Subjective soreness of thigh, hamstring, and gluteal muscles increased (P < 0.05) to 90 ± 14, 93 ± 11, and 90 ± 13 mm at 24 h after LBE and increased (P < 0.05) to 109 ± 6, 113 ± 8, and 98 ± 8 mm at 48 h after LBE. Point tenderness of leg muscles increased (P < 0.05) to 2.9 ± 0.9 at 24 h after LBE.


View larger version (16K):
[in this window]
[in a new window]
  		Fig. 3.   Plasma IL-6 responses to experiment 2. A: plasma IL-6 concentrations at rest and at 30 min of treadmill exercise during control trial and 2 and 26 h after LBE. B: plasma IL-6 concentrations at rest and at 30 min of treadmill exercise for control trial and 7 h after LBE. * IL-6 values at rest and exercise were higher 7 h after LBE than in control trial, P < 0.05. Values are means ± SE for 8 subjects.

Heat Stress Tests

For experiment 1, all eight subjects were able to complete the 50 min of exercise after UBE. During the 25- and 30-h trials after LBE, three subjects discontinued exercise after 30-35 min because of leg discomfort. An additional subject did not participate in the 25- and 30-h trials after LBE because of a diagnosed strain of the bicep and forearm muscles consequent to UBE. Preexercise osmolality values were also similar across trials (average 282 ± 1 mosmol/kgH2O). Preexercise body weights remained similar to baseline values at 6-, 25-, and 30-h trials after UBE, averaging 76.6 ± 3.1 kg, but body weights at the 30-h trial after LBE were higher (P < 0.05) than afternoon baseline body weights (n = 7, 75.2 ± 2.6 vs. 74.6 ± 2.7 kg). Metabolic rate averaged 625 ± 35 and 643 ± 32 W for the morning and afternoon control trials, respectively.

For experiment 1, esophageal, rectal, and mean body temperatures before and during exercise were similar (P > 0.05) to control values after UBE during the 6-, 25-, and 30-h trials. Esophageal temperatures at 50 min of exercise averaged 38.1 ± 0.1 and 38.0 ± 0.1°C at 24 h after UBE and at the morning control trial, respectively, and 38.1 ± 0.1, 38.1 ± 0.1, and 38.1 ± 0.1°C 6 h after UBE, 30 h after UBE, and at the afternoon control trial, respectively. Local sweating and heart rate responses were similar to control values at 6, 25, and 30 h after UBE. Although subject attrition hindered interpretation of the body temperature responses after LBE, 0.3°C higher esophageal and rectal temperatures in two subjects during the 6-h trials suggested some effect of muscle injury on thermoregulation (data not shown). These two subjects had the highest creatine kinase concentrations (53,156 ± 98 U/l) at 48 h after LBE and the highest IL-6 concentrations of the group during exercise 6 h after LBE (23-26 pg/ml). Local sweating responses were similar to control values during the 6-, 25-, and 30-h trials after LBE. The two subjects with higher core temperatures demonstrated no systematic change in sweating control after muscle injury. Heart rate responses, however, were 11-14 beats/min higher (P < 0.05) 6, 25, and 30 h after LBE.

For experiment 2, all subjects completed the 50 min of treadmill exercise during the 2-, 7-, and 26-h trials after LBE. Preexercise body weights were consistent across trials, averaging 72.48 ± 4.45 and 72.63 ± 4.40 kg in morning and afternoon, respectively. Preexercise osmolality values were also similar across trials (285 ± 1 mosmol/kgH2O). Metabolic rate was increased (P < 0.05) from 672 ± 44 W during control trials to 720 ± 52 and 711 ± 47 W during heat stress tests 2 and 7 h after LBE, respectively. During the 26-h trial after LBE, however, metabolic rate had returned to baseline levels.

For experiment 2, esophageal temperatures were similar at rest before and after LBE but were higher (P < 0.05) from 40 to 50 min of exercise during the 2- and 7-h trials than in control heat stress tests (Fig. 4). Rectal temperatures showed a similar pattern of response, averaging 0.2°C higher (P < 0.05) after 50 min of exercise during the 7-h trials than control. Mean body temperatures also increased to higher (P < 0.05) values at 40 and 50 min of exercise during the 2- and 7-h trials than control. Heat storage was greater (P < 0.05) during the 2-h (57 ± 2 vs. 46 ± 2 W/m2) and 7-h (54 ± 4 vs. 42 ± 2 W/m2) trials after LBE. Heart rates were elevated (P < 0.05) after LBE, with values averaging 12, 12, and 8 beats/min higher during the 2-, 7-, and 26-h trials, respectively, than in control heat stress tests (143 ± 3 and 147 ± 3 beats/min in morning and afternoon, respectively). Local sweating responses were not altered from control levels 7 h after LBE (Table 2) or 2 or 26 h after LBE.


View larger version (21K):
[in this window]
[in a new window]
  		Fig. 4.   Experiment 2 esophageal temperature responses to exercise. A: esophageal temperature responses 2 and 26 h after LBE compared with control trial. B: esophageal temperature responses 7 h after LBE compared with control trial. * Esophageal temperatures 2 and 7 h after LBE were higher than control trial values, P < 0.05. Values are means ± SE for 8 subjects.


                              
View this table:
[in this window]
[in a new window]
  		Table 2.   Upper arm sweating responses to treadmill exercise during control trial and 7 h after LBE

Simple regression analysis revealed that the change in energy expenditure could account for 49% and 46% of the variance in the elevated mean body temperature 2 and 6-7 h after LBE, respectively (Fig. 5). However, when the same relationship was examined using repeated-measures regression (8) that combined both time intervals (2 and 7 h after LBE), there was no longer any relationship between the greater energy expenditure and the elevated mean body temperature. Nevertheless, <50% of the variability in response could be accounted for by increased energy cost of exercise, suggesting that other factor(s) contributed to the greater heat storage and elevated body temperatures. Examination of the individual data revealed no pattern between the increase in heat storage and body mass or the increase in mean body temperature and body mass. A subsequent analysis comparing IL-6 values with the increased mean body temperature 7 h after LBE revealed a positive relationship between these variables, suggesting that the systemic inflammatory response may have contributed to the higher body temperatures. However, when 6-h post-LBE data from experiment 1 were included in the correlation analysis, there was no longer any relationship between IL-6 and higher body temperatures (Fig. 6) after LBE. Similarly, the added thermal strain after LBE was not related (P > 0.05) to muscle soreness (r = 0.47 at 6-7 h) or peak creatine kinase levels (r = 0.22).


View larger version (35K):
[in this window]
[in a new window]
  		Fig. 5.   Correlation between the increase in energy expenditure and additional increase in mean body temperature (Tb, by use of rectal and mean skin temperatures) consequent to LBE. , 2 h after eccentric exercise; open circle , 6-7 h after eccentric exercise.



View larger version (30K):
[in this window]
[in a new window]
  		Fig. 6.   Relationship between preexercise IL-6 concentration and the additional increase in mean body temperature (by use of rectal and mean skin temperatures) consequent to LBE. , 2 h after eccentric exercise; open circle , 6-7 h after eccentric exercise; black-down-triangle , 26 h after eccentric exercise. Regression line and 95% confidence intervals are for 6- to 7-h trial only. ns, Not significant.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The primary objective of this study was to determine whether muscle injury and the accompanying inflammatory response would adversely affect thermoregulation, resulting in greater thermal strain during exercise-heat stress. Also, we were interested in how long the thermoregulatory effects would persist. To accomplish these objectives, it was important to have consistent thermoregulatory responses to a given exercise-heat stress. This was accomplished by acclimating the volunteers to heat before testing and including baseline trials that controlled for the circadian effects on body temperature. Additionally, we used two baseline trials to have a good estimate of the typical thermoregulatory response to the exercise-heat challenge.

UBE and LBE protocols were successful at producing muscle soreness to a diffuse area of the upper body and lower body, respectively, and were accompanied by significant increases in creatine kinase, which is a plasma marker of muscle injury. Although neither soreness nor creatine kinase levels are quantitative regarding the extent of muscle fiber injury, they are indicative that muscle injury occurred. The protocol produced sufficient soreness: several individuals in experiment 1 were unable to complete the 50-min treadmill exercise test 24 h after the LBE. The creatine kinase levels obtained within 48 h of the eccentric exercise were as high as or higher than those in other studies that provide evidence in support of muscle z-line streaming, muscle swelling, muscle IL-1beta accumulation, and neutrophil infiltration (6, 13, 15). Therefore, the elevated creatine kinase levels and soreness ratings in the present research are probably indicative of muscle fiber injury and not simply sarcolemma damage.

Associated with the changes in muscle soreness and biochemical indexes of muscle injury were sustained increases in the WBC count. During the 26 h after eccentric exercise in experiment 2, the total WBC count was increased because of increased numbers of granulocyctes, lymphocytes, and monocytes. Increased numbers of circulating neutrophils and monocytes have been reported during the initial hours after eccentric exercise (14, 17) and accumulate at the site of muscle injury during the acute inflammatory response (6, 13). Although the eccentric exercise protocol used to injure the upper body muscles was unable to produce increased IL-6 concentrations, eccentric exercise of the lower body muscles produced a transient increase 6-7 h after injury. These results are consistent with the results from eccentric exercise protocols in which arm (15) and leg muscles (2) were used. These immunologic changes provide supportive evidence that the exercise protocol successfully injured the muscles and produced an inflammatory response.

Despite the high ratings of soreness and elevated creatine kinase levels, core temperature responses to the exercise-heat stress after UBE remained similar to baseline responses 6, 25, and 30 h after UBE. These data suggest that upper body muscle injury had little impact on thermoregulation. However, plasma IL-6 concentrations were similar to baseline levels 6, 25, and 30 h after UBE. It may be that the UBE protocol was not sufficient to produce a systemic immunomodulatory response. Therefore, all that can be concluded from the UBE protocol is that muscle injury per se does not increase the heat strain of subsequent exercise-heat stress.

The LBE protocol not only produced muscle soreness and elevated creatine kinase levels but also it resulted in a transient increase in plasma IL-6 concentration at ~6-7 h after eccentric exercise. Interestingly, muscle soreness values were similar after UBE and LBE, despite possibly higher creatine kinase levels and the elevated IL-6 concentration after LBE. Exercise-heat stress performed at 7 h after LBE resulted in a small but consistent increase in heat storage and core temperatures. The same exercise performed 26 h after LBE (when IL-6 concentration was no longer elevated above control levels) did not increase heat storage or core temperatures. These findings support the hypothesis that acute diffuse muscle injury, which produces systemic immunomodulatory effects, can increase heat strain during exercise. However, there was no relationship between IL-6 concentration and core temperature increase during exercise 6-7 h after LBE. Furthermore, we were unable to detect any changes in threshold temperature for sweating onset or in sweating sensitivity 6-7 h after eccentric exercise when IL-6 was elevated. These two observations suggest that the added heat strain was due to impairment of dry heat loss and/or greater heat production and/or may have been independent of the IL-6 responses.

The higher body temperatures during exercise 2 and 7 h after LBE were associated with greater energy expenditure and presumably heat production, inasmuch as metabolic rate was increased 54 ± 13 and 33 ± 9 W (+5-8%), respectively, during these two trials. Mathematical models (12) that predict core temperature responses during exercise indicate that core temperature should increase ~0.1°C for every 40-W increment in heat production under the climatic conditions of this study. Although data variability and the limited number of data points make a definitive statement impossible, the slope of the mean body temperature (from esophageal and rectal measurements)-to-metabolic rate relationship suggested ~0.1 and 0.2°C increase for every 40-W increase during the 2-h (r = 0.62 and 0.7) and 6- to 7-h (r = 0.51 and 0.74) trials, respectively. These relationships suggest that a portion of the added heat strain after LBE can be attributed to the decreased economy of walking (and presumably greater heat production), likely from modified gate and/or greater motor unit recruitment due to stiffness and/or muscle weakness consequent to performing the LBE protocol.

Other studies using the eccentric exercise model to induce muscle soreness and injury have documented a persistent reduction in muscle strength for days after the eccentric exercise bout (10, 13, 15, 25). Animal models using eccentric exercise to injure the muscle fibers have reported reductions in contraction economy (25) and impaired sarcoplasmic reticulum calcium handling (10) in the injured muscle fibers. If the same responses were present in this study, they may account for the added energy cost of exercise 2 and 6-7 h after the eccentric exercise.

Does the inflammatory response accompanying acute, diffuse muscle injury alter thermoregulation? Is muscle injury a risk factor contributing to heat illness? In these experiments, we chose an experimental model that produced muscle injury and soreness to a diffuse muscle mass to test whether small injury to many areas would illicit a systemic inflammatory response that could alter the thermoregulatory response to exercise. The results of experiment 2 demonstrate a very modest increase in heat strain, despite producing fairly substantial muscle soreness and relatively high plasma creatine kinase concentrations. Although the group mean creatine kinase value at 48 h after LBE averaged 15,634 ± 6,734 U/l, three of eight individuals had values ranging from 22,571 to 52,669 U/l. In the population tested, the largest individual increase above baseline core temperature was 0.4°C, a value similar to what would be expected from someone dehydrated by 2-3% body weight. We also were unable to detect a significant difference in local sweating control responses for the group, and the individuals with highest creatine kinase and IL-6 values did not show any consistent pattern that would suggest altered sweating threshold or sensitivity in response to muscle injury. Therefore, if the local inflammatory response accompanying muscle injury mediated adverse thermoregulatory effects during the exercise-heat stress chosen for the present research, the effects appear to be relatively minor in otherwise healthy persons acclimated to working in hot climates.

Whether persons with a history of severe heat exhaustion or heat stroke respond similarly to the population tested is not known. Although our data demonstrate greater heat storage after muscle injury and subsequent inflammatory response, we did not observe any indication of changes in thermoregulatory control. It may be that certain persons, or any person if predisposed by unknown factors (e.g., dehydration, sickness), might have greater "sensitivity" to the inflammatory response at a given point in time. This type of response has been reported after immunoadjuvant exposure (23). If exercise heat stress is performed when a person is "susceptible," then exertional heat injury could follow. Our data show the possibility of such a relationship, but a stronger link is needed between the inflammatory response and thermoregulatory control changes before this hypothesis becomes more viable.

In summary, we examined whether acute muscle injury and the accompanying inflammatory responses would augment the heat strain accompanying exercise-heat stress. The studies revealed a small but consistent increase in body core temperatures when exercise-heat stress was performed 2-7 h after muscle injury to the leg muscles. Although the mechanisms responsible for the increased heat strain remain unclear, the higher body core temperatures could not be attributed solely to decreased walking economy and occurred during the early inflammatory response, as indicated by elevated plasma IL-6 concentrations and WBC numbers.


    ACKNOWLEDGEMENTS

We thank the volunteers for their willingness to participate in these difficult experiments and Laurie Blanchard, Bruce Cadarette, Jamie Kain, Leslie Levine, Jerry Newcomb, Amy Rouse, Kyle Spears, and Janet Staab for excellent technical assistance.


    FOOTNOTES

The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy, or decision.

Address for reprint requests and other correspondence: S. J. Montain, Thermal and Mountain Medicine Div., US Army Research Institute of Environmental Medicine, Natick, MA 01760-5007 (E-mail: scott.montain{at}na.amedd.army.mil).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Received 22 December 1999; accepted in final form 13 April 2000.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

1.   Anderson, RJ, Reed G, and Knochel J. Heatstroke. Adv Intern Med 2828: 115-140, 1983.

2.   Bruunsgaard, H, Galbo H, Halkjaer-Kristensen J, Johansen TL, MacLean DA, and Pedersen BK. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. J Physiol (Lond) 499: 833-841, 1997[ISI].

3.   Cannon, JG, Meydani SN, Fielding RA, Fiantarone MA, Meydani M, Farhangmehr M, Orencole SF, Blumberg JB, and Evans WJ. Acute phase response in exercise. II. Associations between vitamin E, cytokines, and muscle proteolysis. Am J Physiol Regulatory Integrative Comp Physiol 260: R1235-R1240, 1991[Abstract/Free Full Text].

4.   Costill, DL, Pascoe DD, Fink WJ, Robergs RA, Barr SI, and Pearson DR. Impaired muscle glycogen resynthesis after eccentric exercise. J Appl Physiol 69: 46-50, 1990[Abstract/Free Full Text].

5.   Epstein, Y, Moran DS, Shapiro Y, Sohar E, and Shemer J. Exertional heat stroke: a case series. Med Sci Sports Exerc 31: 224-228, 1999[ISI][Medline].

6.   Fielding, RA, Manfredi TJ, Ding W, Fiatarone MA, Evans WJ, and Cannon JG. Acute phase response in exercise. III. Neutrophil and IL-1beta accumulation in skeletal muscle. Am J Physiol Regulatory Integrative Comp Physiol 265: R166-R172, 1993[Abstract/Free Full Text].

7.   Gardner, JW, Kark JA, Karnei K, Sanborn JS, Gastaldo E, Burr P, and Wenger CB. Risk factors predicting exertional heat illness in male Marine Corps recruits. Med Sci Sports Exerc 28: 939-944, 1996[ISI][Medline].

8.   Glantz, SA, and Slinker BK. Primer of Applied Regression and Analysis of Variance. New York: McGraw-Hill, 1990, p. 381-390.

9.   Graichen, H, Rascati R, and Gonzalez RR. Automatic dew-point temperature sensor. J Appl Physiol 52: 1658-1660, 1982[Abstract/Free Full Text].

10.   Ingalls, CP, Warren GL, Williams JH, Ward CW, and Armstrong RB. E-C coupling failure in mouse EDL muscle after in vivo eccentric contractions. J Appl Physiol 85: 58-67, 1998[Abstract/Free Full Text].

11.   Kark, JA, Burr PQ, Wenger CB, Gastaldo E, and Gardner JW. Exertional heat illness in Marine Corps recruit training. Aviat Space Environ Med 67: 354-360, 1996[Medline].

12.   Kraning, KK, and Gonzalez RR. A mechanistic computer simulation of human work in heat that accounts for physical and physiological effects of clothing, aerobic fitness, and progressive dehydration. J Therm Biol 22: 331-342, 1997.

13.   MacIntyre, DL, Reid WD, Lyster DM, Szasz IJ, and McKenzie DC. Presence of WBC, decreased strength, and delayed soreness in muscle after eccentric exercise. J Appl Physiol 80: 1006-1013, 1996[Abstract/Free Full Text].

14.   Malm, C, Lenkei R, and Sjödin B. Effects of eccentric exercise on the immune system in men. J Appl Physiol 86: 461-468, 1999[Abstract/Free Full Text].

15.   Nosaka, K, and Clarkson PM. Changes in indicators of inflammation after eccentric exercise of the elbow flexors. Med Sci Sports Exerc 28: 953-961, 1996[ISI][Medline].

16.   Ostrowski, K, Rohde T, Zacho M, and Pedersen BK. Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running. J Physiol (Lond) 508: 949-953, 1998[Abstract/Free Full Text].

17.   Pizza, FX, Mitchell JB, Davis BH, Starling RD, Holtz RW, and Bigelow N. Exercise-induced muscle damage: effect on circulating leukocyte and lymphocyte subsets. Med Sci Sports Exerc 27: 363-370, 1995[ISI][Medline].

18.   Ramanathan, NL. A new weighting system for mean surface temperature of the human body. J Appl Physiol 19: 531-533, 1964[Abstract/Free Full Text].

19.   Sawka, MN. Body fluid responses and hypohydration during exercise-heat stress. In: Human Performance Physiology and Environmental Medicine at Terrestrial Extremes, edited by Pandolf KB, Sawka MN, and Gonzalez RR.. Indianapolis, IN: Benchmark, 1988, p. 227-266.

20.   Sawka, MN, Young AJ, Latzka WA, Neufer PD, Quigley MD, and Pandolf KB. Human tolerance to heat strain during exercise: influence of hydration. J Appl Physiol 73: 368-375, 1992[Abstract/Free Full Text].

21.   Shibolet, S, Coll R, Gilat T, and Sohar E. Heatstroke: its clinical picture and mechanism in 36 cases. QJM 36: 525-548, 1996.

22.   Stitt, JT, and Shimada SG. Enhancement of the febrile responses of rats to endogenous pyrogen occurs within the OVLT region. J Appl Physiol 67: 1740-1746, 1989[Abstract/Free Full Text].

23.   Stitt, JT, and Shimada SG. Immunoadjuvants enhance the febrile responses of rats to endogenous pyrogen. J Appl Physiol 67: 1734-1739, 1989[Abstract/Free Full Text].

24.   Tidball, JG. Inflammatory cell response to acute muscle injury. Med Sci Sports Exerc 27: 1022-1032, 1995[ISI][Medline].

25.   Warren, GL, Williams JH, Ward CW, Matoba H, Ingalls CP, Hermann KM, and Armstrong RB. Decreased contraction economy in mouse EDL muscle injured by eccentric contractions. J Appl Physiol 81: 2555-2564, 1996[Abstract/Free Full Text].

J APPL PHYSIOL 89(3):1123-1130


This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. D. Bradford, J. D. Cotter, M. S. Thorburn, R. J. Walker, and D. F. Gerrard
Exercise can be pyrogenic in humans
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R143 - R149.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
L. A. Sonna, C. B. Wenger, S. Flinn, H. K. Sheldon, M. N. Sawka, and C. M. Lilly
Exertional heat injury and gene expression changes: a DNA microarray analysis study
J Appl Physiol, May 1, 2004; 96(5): 1943 - 1953.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Montain, S. J.
Right arrow Articles by Sawka, M. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Montain, S. J.
Right arrow Articles by Sawka, M. N.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online