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The Effect of Oral Vs. Intravenous Rehydration on Circulating Myoglobin and Creatine Kinase

Beasley, Kathleen N1,2; Lee, Elaine C1; McDermott, Brendon P1; Yamamoto, Linda M1; Emmanuel, Holly1; Casa, Douglas J1; Armstrong, Lawrence E1; Kraemer, William J1; Maresh, Carl M1

The Journal of Strength & Conditioning Research: January 2010 - Volume 24 - Issue 1 - p 60-67
doi: 10.1519/JSC.0b013e3181c63c4e
Original Research

Beasley, KN, Lee, EC, McDermott, BP, Yamamoto, LM, Emmanuel, H, Casa, DJ, Armstrong, LE, Kraemer, WJ, and Maresh, CM. The effect of oral vs. intravenous rehydration on circulating myoglobin and creatine kinase. J Strength Cond Res 24(1): 60-67, 2010-Physical activity of significant intensity and duration may cause varying degrees of skeletal muscle damage, but it is unclear whether mode of rehydration will attenuate muscle tissue disruption caused by exercise in the heat. To examine the effects of the mode of rehydration on markers of muscle damage (myoglobin and creatine kinase [CK]), 11 healthy active men (age = 23 ± 4 years, body mass = 80.9 ± 3.9 kg, height = 180.5 ± 5.4 cm) completed 4 experimental trials consisting of an exercise dehydration protocol (to −4% of baseline body mass), followed by a rehydration period (oral, intravenous [IV], oral and IV combined, and ad libitum), and finishing with an intense exercise challenge that included treadmill running and sprinting and a box lifting protocol. During rehydration, subjects returned to −2% of baseline body mass unless completing the ad libitum trial during which they consumed fluids as thirst dictated. Myoglobin (Mb) and CK were measured during euhydrated rest. Post-exercise blood was drawn at 1 and 24 hours post exercise challenge for Mb and CK, respectively. Urine was collected during euhydrated rest and 1-hour post exercise challenge for measurement of Mb clearance. Mb concentrations increased significantly from pre (1.06 ± 0.20, 0.88 ± 0.07, 1.15 ± 0.25 and 0.92 ± 0.06 nmol·L−1) to post (1.52 ± 0.28, 1.44 ± 0.11, 1.71 ± 0.45 and 1.58 ± 0.39) for IV, oral, oral and IV combined, and ad libitum, respectively, but were not significantly different among trials. Serum CK concentrations remained within the normal physiological range for all trials. Thus, despite previous research that clearly indicates the benefit of ingesting fluids during exercise to attenuate muscle damage, there were no significant differences between the modes of rehydration on circulating Mb and CK.

1Department of Kinesiology, University of Connecticut, Storrs, Connecticut; and 2Military Performance Division, USARIEM, Natick, Massachusetts

Research was conducted at the University of Connecticut Human Performance Laboratory.

Address correspondence to Carl M. Maresh,

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Physical activity of significant intensity and duration may cause varying degrees of skeletal muscle damage. Exercise in a hot environment results in more muscle damage because heat as an added stress exacerbates muscle tissue disruption (9). One indirect indicator of muscle damage is the measurement of circulating proteins and enzymes, such as myoglobin (Mb) and creatine kinase (CK), after intense exercise. Muscle damage is not the only performance-inhibiting factor related to combined exercise and heat stress. Heart rate reaches a maximal level, whereas stroke volume decreases, leading to decreased cardiac output (5). The cardiovascular system will also be compromised because the demand for blood supply to the skin (for thermoregulation) may override cardiovascular potential (5,23).

Further impairments of physiologic parameters can arise when an athlete exercises in a dehydrated state. Hypohydration may lead to increased core temperature as a result of reduced blood volume, skin blood flow, and sweat rate (20,27), and an increased cardiovascular strain is associated with body water loss, hypovolemia, peripheral vasodilation, tachycardia, decreased venous return, and decreased stroke volume (11,24). In addition, it has been speculated that the negative effects of hypohydration on cell water volume, muscle metabolism (via glycogen depletion), and the cardiovascular system (via reduced blood flow to the skeletal muscles) may cause abnormal stress levels on the muscle cells, which could lead to cell membrane permeability and consequently increased levels of CK and Mb in the blood (26). Thus, rehydration is imperative. In addition to the traditional rehydration method of oral fluid ingestion, intravenous (IV) rehydration has become a common scenario for athletes, laborers, and military personnel (17).

Performance and physiologic factors may be enhanced if both dehydration and muscle damage are attenuated. Previous investigations reported significant muscle damage in hypohydrated participants (9,26), indicating the potential for attenuation of muscle damage through maintenance of the hydration status. Although research indicates that maintaining hydration through oral fluid ingestion during exercise results in significantly less muscle damage than no fluid ingestion (26), there is no evidence that IV rehydration leads to decreased muscle damage compared with oral rehydration. Mode of rehydration could potentially play a key factor in affecting circulating Mb and CK. Because IV infusion affects plasma volume more quickly than oral ingestion of fluids (5,6), and the solubility of Mb has been shown to decrease during periods of hypohydration (28), it could be speculated that the solubility of Mb and CK will be affected immediately with IV rehydration. This could lead to increased clearance of such markers of muscle damage from the blood and in turn lead to lower concentrations when measured in subjects post rehydration.

Rehydration may aid in maintaining cell water volume within the muscles, thus limiting the physiological strain on individual muscle fibers and consequently limiting total muscular damage (26). Therefore, the main objective of the proposed study was to determine if a combination of IV and oral (IV/O) rehydration is superior to oral rehydration alone, IV rehydration alone, or ad libitum fluid consumption in attenuating markers of muscle damage during a subsequent intense exercise bout performed in the heat. Based on previous research on dehydration and muscle damage, in addition to the slower response in plasma volume restoration to oral rehydration (2), we hypothesized that the highest concentrations of muscle damage markers would be present after the ad libitum trial. We further hypothesized that the immediate physiological responses seen with IV rehydration (i.e., increased plasma volume and efficient physiologic restoration) coupled with the benefits associated with consuming fluids orally (i.e., increased splanchnic circulation and more efficient lactate removal) would result in the lowest concentrations of circulating myoglobin and CK.

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Experimental Approach to the Problem

This study used a carefully controlled, random, crossover design during which subjects completed 4 controlled trials each separated by at least 1 week. Each experimental trial was the same except for the hydration treatment employed. Each trial included 4 distinct components: overnight dehydration, exercise dehydration (EXDE), rehydration (REHY), and an exercise challenge (EXCH). The 4 REHY trials included controlled oral, controlled IV, controlled half oral and half intravenous (IV/O), and ad libitum oral. The oral fluid was a flavored noncaloric electrolyte (0.45% NaCl) beverage, and the IV fluid was half-normal saline (0.45% NaCl). Before fluid administration, fluids were placed in a cooler containing commercially available chemical cold packs to ensure that IV and oral fluids were the same temperature for rehydration. Muscle damage markers were measured during euhydrated rest, 24 hours before exercise, and at 1 and 24 hours post. The study was conducted between the months of November and February. Outdoor temperatures during this time were colder than the chamber testing conditions, but the routine exposure to the chamber helped the subjects maintain their level of heat acclimation during the study.

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Eleven healthy active men (age = 23 ± 4 years, range = 19-30 years; height = 180.5 ± 5.4 cm, range = 173-190 cm; mass = 80.9 ± 3.9 kg, range = 76.1-88.5 kg; o2max = 57.0 ± 4.3 ml·kg−1·min−1, range = 50.4-65.0 ml·kg−1·min−1) volunteered to participate in this study. All subjects were involved recreationally in both weightlifting and cardiovascular exercise. Regardless of training background and their regular exercise regimen, all subjects were required to have a o2max above 50.0 ml·kg−1·min−1 in the heat to participate in the study. Subjects were recruited via flyers, class announcements, and the University's online list serve. Before any familiarization or testing sessions, each subject signed an informed consent statement that had been approved by the University Institutional Review Board. All subjects completed medical history forms and received clearance before participation in any part of the study. Subjects were financially compensated for their participation in this study.

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To adequately familiarize each subject with the equipment and methods used during experimental days, subjects came to the Human Performance Laboratory for 5 preliminary testing sessions. For all familiarizations, each subject arrived after a 12-hour overnight fast (no food or fluid, except water) and 24 hours without exercising, drinking alcohol, or consuming any stimulants (including caffeine). To ensure adequate hydration status, investigators asked the subject to consume 1 L of water before going to sleep the night before arriving in the laboratory and upon wakening the morning of the visit. Researchers instructed the subject to continue his normal diet and exercise regimen throughout the study. To standardize each trial, each subject maintained exercise and diet logs for 72 hours before each experimental day. Subjects were asked to repeat their diet for the 24-hour period before testing for all experimental days. All practice exercises for familiarizations took place in the environmental chamber at the same temperature and humidity that was set for experimental trials.

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Familiarization 1

Data on height, weight, and body dimensions were collected. Investigators then demonstrated all the exercises (repetitive box lifting, cycling, and treadmill running) that would be completed by the subject on the experimental days. Repetitive box lifting was a self-paced exercise consisting of lifting a 20.5-kg box with handles from the floor to a 1.32-m high platform as rapidly and as frequently as possible in a given time frame (18,21). Investigators used 2 boxes and slid them down a ramp from the platform to the floor after each lift. This ensured that a box was always available for the next lift without interruption. After the demonstration, the subject practiced the exercise for approximately 5 minutes. Additionally, the subject completed an 800-m performance run to become familiar with pacing and performance for experimental trials; this was an all-out run during which the subject ran as quickly as possible to complete the 800 m.

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Familiarization 2

The subject completed a maximal aerobic power assessment (o2max). This test entailed 10-15 minutes of progressive incremental running on a motorized treadmill to volitional fatigue. o2 (ParvoMedics, Sandy, UT, USA), heart rate (HR) (Vantage, Polar Electro, Woodbury, NY, USA), and ratings of perceived exertion (RPE) were measured periodically throughout the test. Specific criteria (plateau in o2 with increasing exercise intensity, RPE ≥ 18, HR = age-predicted maximum) ensured that o2max was attained. After 20 minutes of rest, the subject ran for at least 2 minutes at the speed and incline at which he stopped in the first bout of exercise. This was a test to confirm the maximum value obtained in the first bout of exercise.

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Familiarization 3

During this visit, researchers verified values for the subject for 40-50% o2max on a cycle and 50-60% o2max on a treadmill to be used for experimental days.

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Familiarization 4

The subject performed a warm-up by performing a few squat exercises on a Smith machine. The subject rested for a short period, then performed 4 sets of 5-10 squat repetitions at 80-90% of his estimated squat repetition maximum. Adequate rest was given between sets. This procedure was performed to minimize the soreness felt after the first experimental day.

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Familiarization 5

The subject completed the 3 exercises (walking/running, cycling, and box lifting) with a variety of monitoring apparatus (i.e., rectal probe, head gear, and HR monitor) on. This was done to minimize some of the stress and anxiety related to the monitoring apparatus before experimental testing.

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Experimental Trial

Twenty-four hours before the experimental trial, subjects came to the laboratory for a preliminary visit to establish baseline body mass after a 12-hour overnight fast (no food or fluid, except water) and 24 hours without exercising, drinking alcohol, or consuming any stimulants (including caffeine). To ensure adequate hydration status, investigators asked the subject to consume 1 L of water before going to sleep the night before arriving to the laboratory and upon wakening the morning of the visit. During the preliminary visit, researchers measured the subject's mass and collected a baseline blood and urine sample. The subject voided and researchers analyzed the urine for osmolality (Uosm) via freezing point depression (Model 3250; Advanced Instruments, Inc., Norwood, MA, USA) and specific gravity (Usg) via refractometry (A300CL-E01; Atago, Tokyo, Japan) to document euhydration; Usg ≤ 1.020 was defined as euhydration (10). Blood measures are described below. Blood was drawn from an antecubital vein using a 20-gauge needle. Researchers instructed subjects to abstain from exercise, alcohol, and stimulants (including caffeine) for the remainder of the day. Beginning at 1,200 hours, subjects refrained from drinking fluids and eating high moisture foods.

The following morning the subject arrived at the laboratory for experimental testing. Researchers recorded the subject's mass, collected a urine sample to verify hydration state (goal status was -1 to -2% body mass), and provided the subject with a rectal thermistor to position 10 cm beyond the anal sphincter (TR, Model 401; Yellow Springs Instruments, Yellow Springs, OH, USA). The subject then consumed a standard meal (bagel, banana, and 0.3 g of cream cheese) provided by the researchers. A trained phlebotomist then inserted a 20-gauge Teflon cannula kept patent with normal saline and heparin (9:1) into antecubital veins of both arms. Cannulas were inserted in both arms for all trials to control stress level associated with the insertion and also to ensure the subject was blinded to the trial before actual fluid replacement.

The subject then entered the environmental chamber (36°C, 40% relative humidity, Model 2000; Minus Eleven, Inc., Malden, MA, USA). The subject sat inside the chamber for a 15-minute equilibration period before performing any exercise tasks. For EXDE, the subject alternated between walking on a motorized treadmill at 50-60% O2max and cycling on an ergometer at 40-50% o2max. Body mass, HR, and TR were monitored at 15-minute increments. For EXDE, the subject walked/cycled for 2 hours with 30-minute segments of walking and cycling. The goal hypohydration status after EXDE was to attain −4% of baseline body mass.

After completing the EXDE, the subject sat comfortably for 30 minutes for REHY (via 1 of the 4 methods: oral, IV, IV/O, and ad libitum) to −2% of baseline body mass, except for the ad libitum trial. For the ad libitum trial, the subject drank as his thirst dictated, regardless of the percent body mass reached. For the remaining 30 minutes before the EXCH, researchers monitored the subject for physiologic recovery of dehydration.

After the 1-hour REHY period, the subject began the EXCH. The EXCH began with 25 minutes of running on the treadmill at 55-60% o2max. Immediately after this run, the subject performed a maximal effort 800-m run. Subjects rested for 5 minutes before beginning the box lifting protocol. The subject performed the box lifting for 5 minutes at a maximal pace, lifting as many boxes as he could during that period.

Immediately after the EXCH, the subject remained seated in the heat chamber for a 1-hour recovery period. Blood was drawn 60-minute post EXCH. Researchers provided the subject with instructions for proper rehydration after the trial and a time to return the following day for the 24-hour post-exercise blood draw.

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Thermoregulatory Measures

TR was measured every 15 minutes during EXDE, every minute during the first 30 minutes of REHY, every 5 minutes during the second 30 minutes of REHY, and every other minute during the running portion of the EXCH. TR was also measured immediately post EXCH.

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Cardiovascular Measures

Heart rate was measured every 15 minutes during EXDE, every minute during the first 30 minutes of REHY, every 5 minutes during the second 30 minutes of REHY, and every other minute during the running portion of the EXCH. Heart rate was also measured every minute during box lifting.

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Blood Analysis

Blood samples were aliquoted into plain or EDTA-treated tubes (Vacutainer; Becton Dickinson, Franklin Lakes, NJ, USA) at 3 time points for the measurement of muscle damage markers: 24 hours before exercise; 60 minutes and 24 hours post EXCH. The preliminary blood draw at 24 hours before exercise allowed the researchers to determine the subject's baseline levels of myoglobin, CK, hemoglobin, hematocrit, and serum osmolality in a euhydrated state. Blood was collected at 60 minutes and 24 hours post EXCH to determine if hydration status or mode of rehydration affected the levels of myoglobin and CK, respectively. Hemoglobin, hematocrit, and serum osmolality measures permitted us to track the effects of exercise and hydration status on the subjects.

The 1-hour post blood draw was previously identified as a peak for Mb after exercise (22). The 24-hour blood draw was previously identified as a peak for CK after exercise (1,16,22,29). After all blood draws, researchers immediately assessed an aliquot of plasma for hematocrit (Hct) in triplicate via microcapillary technique and hemoglobin (Hb) in duplicate (Hb 201+; HemoCue, Ängelholm, Sweden) for percent change of plasma volume (12). The remaining whole blood was centrifuged at 1,500g for 15 minutes at 4°C. Serum was measured in duplicate for osmolality (Sosm) via freezing point depression (3DII; Advanced Digimatic, Needham Heights, MA, USA). Plasma was aliquoted and frozen (−80°C) for subsequent duplicate analysis of myoglobin via microwell enzyme-linked immunosorbent assay (Life Diagnostics, Inc., West Chester, PA, USA) and serum for subsequent duplicate analysis of CK via spectrophotometry (Biomate; Thermo Fisher Scientific, Inc., Waltham, MA, USA).

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Urine Analysis

Baseline Usg and Uosm were used to verify hydration state. Subjects also provided urine samples 60 minutes post EXCH for analysis of Mb (ALPCO Diagnostics, Salem, NH, USA). Urine measures were used to detect clearance rates of Mb post exercise.

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Statistical Analyses

Data are presented as mean ± SE. A repeated measures (condition × time) analysis of variance for Mb and an analysis of covariance (ANCOVA) for CK were used. The ANCOVA was used for CK to account for the variability in baseline values. When appropriate, investigators used the Fisher's post hoc test to determine specific pairwise differences. Researchers set the significance at p ≤ 0.05.

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Hydration indices (body mass, Usg, and Uosm) verified euhydrated status on the pre-trial day (baseline). Baseline Usg was <1.020 and baseline Uosm was <800 mOsm·kg−1 for all trials. Subjects reached the goal hydration status during all trials (4% body mass loss at the conclusion of EXDE) with no significant differences among trials (Figure 1).

Figure 1

Figure 1

Fluid volumes during the rehydration period were not significantly different among trials (Figure 2).

Figure 2

Figure 2

During EXCH, there were no significant differences in the number of boxes lifted among trials (Figure 3A). Rectal temperature showed no significant differences after box lifting among trials (39.03 ± 0.12°C). Heart rate also demonstrated no significant differences among trials; however, there was a significant difference across time points for all trials (Figure 3B). Figure 4 displays the total number of boxes lifted and the average HR for all trials. There were no significant differences among trials in average number of boxes lifted and average HR during the exercise challenge.

Figure 3

Figure 3

Figure 4

Figure 4

Figure 5 displays the Mb response to exercise. Mb values were significantly elevated above corresponding pre-values for all trials (p = 0.019, η2 = 0.436). The response in Mb was not significantly different among trials (p = 0.782, η2 = 0.017). Clearance rates for Mb, measured via urine samples 1 hour post EXCH, were not detectable and therefore not significant.

Figure 5

Figure 5

Creatine kinase did not show a significant difference over time (p = 0.119, η2 = 0.248) or in response to the mode of rehydration (p = 0.645, η2 = 0.200) (Figure 6).

Figure 6

Figure 6

Percent plasma volume change was not significantly different among trials at both 1 hour (p = 0.872, η2 = 0.023) and 24 hours post EXCH (p = 0.962, η2 = 0.009) (Table 1).

Table 1

Table 1

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Contrary to our hypothesis, results from this investigation suggest that markers of muscle damage were not differently affected by the mode of rehydration before strenuous exercise in healthy active men. The response of both CK and Mb showed no significant differences among the 4 most common modes of rehydration in competitive sport. Previous studies have reported that maintaining adequate hydration during exercise has the ability to minimize muscle damage, but these studies used only oral rehydration (8,26).

The 4 modes of rehydration differ in both the psychological and physiological responses. Oral rehydration provides more favorable RPE, thirst, and thermal responses to subsequent exercise in the heat than IV rehydration (4). As a result, the positive psychological benefit may have allowed the subjects to exercise at a higher intensity, thereby incurring more muscle damage. On the other hand, the immediate entry into the systemic vasculature leading to rapid plasma volume restoration of IV rehydration (4) may suggest that IV rehydration attenuates muscle damage more effectively than oral rehydration. Therefore, the combination of the benefits of the oral and IV methods of rehydration was the basis for the hypothesis of the present study.

Subjects began REHY with a 4% body mass loss and rehydrated to approximately 2% for all trials including the ad libitum trial; therefore, the level of hypohydration was not a confounding variable when assessing circulating Mb and CK levels. Thus, the degree of muscle damage sustained was not significantly different among trials regardless of the hydration mode.

The intensity of the exercise challenge was sufficient to result in significant increases in plasma Mb responses at 1 hour post EXCH but not serum CK responses at 24 hours post EXCH. Normal values of CK are difficult to estimate due to individual and population variation in serum levels. Also, large molecular weight of CK makes it more difficult to pass through the cell membrane unless excessive damage is incurred (3,13). Variable baseline values combined with its large size could have contributed to the results of the present study. The lack of a distinct eccentric component during EXCH in addition to the training status of the subjects may have also contributed to the minimal CK response observed. Moreover, CK has been shown to peak up to 7 days after exercise (7). Because the study was part of a larger investigation, subjects exercised between trials to maintain training status. This training could have led to elevated CK levels before the baseline blood draw and therefore resulted in inconsistent baseline values.

The number of boxes lifted and the corresponding HR response during the exercise challenge were not significantly different among trials; however, the IV/O trial reflected a greater number of boxes lifted in addition to a higher average HR. Because of the combined positive effects of both rehydration modes during the IV/O trial, subjects may have been able to work harder. The greater increase in Mb post exercise during the IV/O trial compared with the other modes, although slight, may be a result of the increased workload. However, mode of rehydration alone may not have been enough to overcome this increase in work.

A previous study examining the effects of hydration state and resistance exercise on markers of muscle damage found that increasing levels of hypohydration led to increased circulating Mb after exercise (30). In addition, Seifert et al. (26) found that subjects who consumed a noncaloric fluid during exercise minimized the release of Mb and CK compared with subjects who were fluid restricted. It is important to note that Sosm during the Seifert study was not significantly different between treatments. Such findings emphasize the importance of maintaining hydration to attenuate the release of markers of muscle damage.

Although there were no significant differences among the modes of rehydration in attenuating these muscle damage indices, the lack of a fluid-restricted trial or a trial with significantly less fluid intake may have contributed to the findings of the present study. Without fluids, cellular stress is amplified leading to increased cell membrane permeability and consequently to the leakage of proteins and enzymes into the bloodstream (26). If cell stress is too great, necrosis may also ensue (26). Moreover, exercising while dehydrated leads to increased blood flow to the skin for thermoregulation and decreased blood flow to the muscles (5,19,23). Thus, the ensuing hypoxic conditions may add additional stress on the cell, thereby causing muscle fiber damage. For the safety of our subjects, a fluid-restricted trial was not included; however, we believe that had subjects completed the box lifting without rehydration, the circulating Mb and CK values would have been significantly greater during that trial.

Fluid intake during exercise minimizes glycogenolysis (14,15) and maintains cell water volume, both of which lessen the physiological stress on the muscle fibers (9,26). The solubility of Mb is significantly diminished during periods of hypohydration. This decreased solubility leads to difficulties in the clearance of Mb in the kidneys (28). Because all trials involved rehydration, it is possible that the solubility of Mb was maintained and clearance remained efficient such that high levels of Mb post EXCH were not seen. One explanation for the lack of significant Mb in the urine post EXCH could be that an insufficient amount of muscle mass was damaged. At least 200 g of muscle must be injured to produce enough Mb to be seen in the urine, as in rhabdomyolysis (25).

In addition to the lengthy heat exposure and prolonged fluid restriction before experimental day, the exercise dehydration protocol may have had a significant effect on the exercise challenge performance and thus Mb and CK response. Overall, subjects were fatigued before beginning the exercise challenge and therefore may not have been able to push themselves as hard. As a result, the work intensity, and consequently the damage, may not have been as great as it could have been had the challenge not been preceded by such stresses.

In the future, a more eccentrically focused lifting protocol should be considered for determining the most physiologically beneficial mode of rehydration in attenuating muscle damage. Whereas Mb showed significant increases pre to post, CK remained within the normal physiological range. Had the protocol elicited more damage, significance may have been seen among treatments.

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Practical Applications

Although previous research supports the benefit of fluid ingestion during exercise compared with no fluid intake in minimizing muscle damage (26), the present study demonstrates that muscle damage is not better attenuated by one particular mode of rehydration. Even though IV infusion increases plasma volume, and possibly solubility of Mb and CK, more rapidly than oral rehydration, it appears to provide no specific benefit with regard to muscle damage. Given the combination of physiological performance and safety advantages associated with appropriate hydration practices (2,4,9,26,30), regardless of hydration mode, we strongly recommend athletes and coaches to follow established guidelines for maintaining hydration during and after exercise, especially when performed in a hot environment.

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muscle damage; strenuous exercise; dehydration

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