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J Appl Physiol 104: 639-647, 2008. First published December 13, 2007; doi:10.1152/japplphysiol.00322.2007
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High specific torque is related to lengthening contraction-induced skeletal muscle injury

Christopher D. Black,1 Christopher P. Elder,1 Ashraf Gorgey,2 and Gary A. Dudley{dagger}

1Department of Kinesiology, The University of Georgia, Athens, Georgia; and 2Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan

Submitted 21 March 2007 ; accepted in final form 11 December 2007


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Animal models implicate multiple mechanical factors in the initiation of exercise-induced muscle injury. Muscle injury has been widely studied in humans, but few data exist regarding the underlying cause of muscle injury. This study sought to examine the role of torque per active muscle volume in muscle injury. Eight subjects performed 80 electrically stimulated [via electromyostimulation (EMS)] eccentric contractions of the right and left quadriceps femoris (QF) through an 80° arc at 120°/s. Specific torque was varied by applying 25-Hz EMS to one thigh and 100-Hz EMS to the contralateral thigh. Transverse relaxation time (T2) magnetic resonance images of the QF were collected before and 3 days after the eccentric exercise bouts. Injury was assessed via changes in isometric force and ratings of soreness over the course of 14 days after exercise and by determining changes in T2 and muscle volume 3 days after exercise. The 100-Hz EMS induced greater force loss (P < 0. 05), soreness (P < 0.05), change in muscle volume (P = 0.03), and volume of muscle demonstrating increased T2 (P = 0.005) than the 25-Hz EMS. In addition, injury was found to be similar across the QF in all but the most proximal regions of the QF. Our findings suggest that, in humans, high torque per active volume during lengthening muscle contractions is related to muscle injury.

transverse relaxation time magnetic resonance images; electrical stimulation; muscle activation; soreness

IT IS WELL ESTABLISHED THAT novel exercise, especially exercise involving lengthening muscle actions, can evoke skeletal muscle injury. Data from animal studies have implicated several mechanical factors as the potential underlying cause or initial event in muscle injury. Contraction force (27, 45), contraction velocity (8, 45), initial muscle length (42), muscle strain (8, 23), and number of eccentric contractions (27, 42, 46) have been found to contribute to eccentric exercise-induced muscle injury. These studies were performed on a variety of animal species (rabbits, mice, rats) and used multiple in vitro and in situ protocols to induce skeletal muscle injury. It has been suggested that these differences may account for the disparate findings regarding the relative contribution of each factor to muscle injury (11).

Few human studies have focused on the underlying mechanisms of exercise-induced muscle injury. As shown in animals, performing contractions at long muscle lengths (29) and increasing the number of eccentric contractions (9) have been shown to cause greater injury. However, the role contraction force plays in muscle injury remains unclear. Eccentric actions recruit fewer motor units to generate a given absolute force (10), and it has been suggested that this is the primary reason eccentric actions cause greater injury than their concentric and isometric counterparts (4, 5, 27). Thus it is suggested that it is not high force per se; rather, it is high specific force (force per active area) that is the initial event in exercise-induced injury.

Magnetic resonance imaging (MRI) has been used to measure muscle activation during exercise (1, 2, 7, 16). Exercise increases the transverse relaxation time (T2) of skeletal muscle water. Previous studies have demonstrated that the mean T2 of a recently exercised muscle correlates with exercise intensity (21) and surface EMG (1). When quantified on a pixel-by-pixel basis, the areas of muscle demonstrating increased T2 after electrically stimulated exercise [via electromyostimulation (EMS)] (2, 7) have been found to correlate to torque production, allowing T2 magnetic resonance (MR) images to be used as a relative index of muscle activation during exercise (37). Subsequent to eccentric exercise, a delayed increase in the T2 has been observed that peaks 2–6 days after exercise (12, 39). This delayed increase correlates to histological assessment of muscle injury in both humans (30) and animals (26) and with changes in other traditional markers of muscle injury such as soreness, serum creatine kinase levels, and isometric force loss (7, 12, 38).

A recent study from our laboratory (16) used T2 MR images to demonstrate, within the same thigh, that when stimulation amplitude was held constant, altering EMS frequency from 100 to 25 Hz did not alter the relative area of muscle activated during exercise (16). As a consequence, specific force was 32% lower during 25-Hz EMS (16). Although no data exist that confirm this fact, it seems plausible (if a similar excitatory stimulus was given) that EMS could be used to match active muscle between the right and left quadriceps femoris (QF). If active muscle was matched, specific force could be altered by manipulating stimulation frequency between thighs, and its role in muscle injury could be determined.

The purpose of the present study was to examine the role of force per active area in muscle injury. To accomplish this, two experiments were performed. An initial experiment was performed to determine whether active muscle could be matched between the right and left QF after EMS-evoked isometric exercise. A second experiment was then performed in which two EMS-evoked eccentric exercise protocols were used to manipulate specific force. The first protocol used 25-Hz EMS to evoke a series of 80 eccentric contractions of the QF, whereas in the second protocol 100-Hz EMS was used to evoke 80 eccentric contractions in the contralateral QF. Range of motion and contraction velocity were matched between the protocols, and the magnitude of muscle injury resulting from each was compared. We hypothesized, because of its higher specific force, that 100-Hz EMS would lead to greater muscle injury.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
All experimental procedures were approved by The Institutional Review Board of The University of Georgia, and subjects provided written, informed consent before participation.

Activation Experiments

Subjects.   Seven subjects (5 men and 2 women, age of 26 ± 3 yr, height of 173 ± 5 cm, and mass of 70 ± 12 kg; 2 of which participated in the injury experiment) were randomly assigned to receive 100-Hz EMS during one exercise bout and 25-Hz EMS during the other.

Experimental design.   Subjects performed a series of maximal voluntary isometric contractions (MVIC) with the right and left QF muscle groups to assess maximal voluntary torque production. On a separate day, two bouts of EMS-evoked isometric exercise of the QF were performed. The right and left QF were stimulated simultaneously during each exercise bout; 100-Hz EMS was applied during one bout, and 25-Hz EMS was applied during the other. T2 MR images were acquired at rest (before the first bout of EMS) and immediately (within 5 min) after each of the two exercise bouts. Each exercise bout was separated by ~90 min.

Assessment of MVIC.   Isometric knee extension was performed as described previously (7) on a custom-built chair with the leg secured via an inelastic strap to a rigid lever arm so that the knee was fixed at ~70° below horizontal. The moment arm was established by positioning a load cell (model 2000A; Rice Lake Weighing Systems, Rice Lake, WI) parallel to the line of pull and perpendicular to the lever arm. Torque was recorded from the load cell with a MacLab analog-to-digital converter (model ML 400; ADInstruments, Milford, MA) with a sample rate of 100 Hz. Values were transferred to a portable computer for storage and analysis (Apple Computer, Cupertino, CA). All subjects were well motivated and experienced at performing voluntary knee extension exercise of this type. Subjects performed a series of MVICs of the knee extensors lasting ~3 s. Verbal encouragement was provided during each effort, and at least 2 min of rest was provided between trials. For each effort, torque was measured from the plateau region of the torque tracing. Once two efforts differed by <5%, the average of the two efforts was considered MVIC and recorded for further analysis. Day-to-day reliability of MVIC, assessed in this manner, was pilot tested over 5 consecutive days before this study (unpublished observations). The mean within-subject coefficient of variation was 3.2 ± 2.2% (mean ± SD) and ranged from 0.8% to 8.5% across the testing days. In addition, an intraclass correlation coefficient of 0.99 was found across the 5 testing days.

Electrically stimulated exercise.   Stimulation electrodes (6.98 cm x 10.16 cm; Uni-Patch, Wabasha, MN) were placed on the skin over the distal vastus medialis and the proximal vastus lateralis as described previously (2). EMS electrode placement was marked with indelible ink to ensure similar placement between EMS bouts. Electrode placement was visually similar between the right and left thighs. A commercial stimulator (TheraTouch model 4.7; Rich-Mar, Inola, OK) was used for EMS. Contractions were elicited by a 450-µs square-wave biphasic pulse. The right thigh was used to determine the maximum tolerable EMS amplitude for each subject. This was done to limit cocontraction due to discomfort. Torque elicited at this amplitude at a frequency of 100 Hz was recorded. EMS was then applied to the left thigh, at 100 Hz, to evoke a similar torque. Two bouts of EMS-evoked isometric exercise were then performed; stimulation frequency was randomly set to 100 Hz for one bout and to 25 Hz for the other. Each exercise bout consisted of 30, 2-s contractions with 2 s of rest between contractions. Both the right QF and left QF of each subject were stimulated simultaneously (at the prescribed frequency) during each exercise bout. This protocol was chosen because it is known to induce a contrast shift in T2-weighted MR images (2, 7). Maximal joint torque evoked via EMS was calculated for the right and left QF as the average of the peak torque during the first three contractions of each exercise bout. Previous research has demonstrated that torque from these initial contractions is correlated with muscle mass activated during contraction (2, 7).

MRI.   Total and activated muscles were determined by MRI. Standard T2-weighted spin-echo MR images of the thighs were collected with a 1.5-T super-conducting magnet (Signa; General Electric, Milwaukee, WI). Transaxial images (repetition time/echo time = 1,600/30, 60) were acquired from the proximal border of the patella to the anterior superior iliac spine using 10-mm-thick slices spaced 10 mm apart with a 40-cm field of view and a 256 x 256 matrix. Lower extremity positions within the magnet coil were marked during the initial resting scan (before EMS-evoked exercise) and replicated after exercise to aide in matching regions of interest for all images.

Images were analyzed with WinVessel 1.04 (Meyer, Michigan State University, East Lansing, MI), essentially as described previously (2, 33). After spatial calibration, a region of interest was defined in each image by manually tracing the outline of the anatomic cross-sectional area of the QF. The T2 for each pixel within the region of interest was determined from the preexercise (resting) images. Pixels with a T2 between 20 and 35 ms were assumed to represent muscle in the preexercise images (33). Skeletal muscle activated during EMS-evoked contractions was determined by the contrast shift (elevation of T2) within the muscle. All muscle pixels in post-EMS images with a T2 >1 SD above the mean T2 of pre-EMS muscle in corresponding images were considered activated (2, 33). Active areas in the postexercise images were corrected for pixels containing noncontractile material, such as fat, by subtracting pixels from the preexercise images that demonstrated an elevated T2. The volume (cm3) of each axial section was calculated by multiplying the anatomic cross-sectional area of the section by slice thickness (1 cm) and spacing (1 cm). The volumes of each section and spacing were summed to calculate a volume of the entire QF muscle group. QF muscle volume was calculated from the pre-EMS images, and active volume was determined from post-EMS images after each bout of EMS. Additionally, muscle volume and active volume were separated into 15 regions, each representing 1/15 of femur length (Lf). This was done to aid in the comparison of the amount and spatial location of activated muscle along the length of the femur.

Specific force and specific torque.   Specific force (force per unit area) is an index of the intrinsic capacity of a muscle to generate force and of the stress placed on individual fibers during contraction. Accurate estimations of specific force in vivo require muscle fiber force to be expressed relative to the physiological cross-sectional area (25). Muscle volume, fiber length, pennation angle, and tendon moment arm of the contracting muscle must all be assessed to estimate specific force. Because of the inherent difficulties in determining pennation angle, moment arm, and fiber length of each of the four muscles of the QF muscle group, all required to estimate specific force for the QF muscle group, specific force per se was not calculated in the present study. Instead, force per active area was calculated as the ratio of isometric torque (voluntary or EMS evoked) to QF muscle volume (total or activated) as done previously (15). When calculated in this manner, torque per active muscle volume (specific torque) can be considered a surrogate of specific force (24).

Statistical analysis.   Results are expressed as means ± SD. All statistical tests were performed with SPSS version 14.0. Joint torque, active volume, and specific torque were analyzed with a two-factor leg (right and left) x exercise (MVIC, 25 Hz, 100 Hz) within-subject ANOVA. A three-factor leg (right and left) x stimulation frequency (25 Hz and 100 Hz) x Lf region (1–15) within-subject design was used to determine whether differences were present in the location of active muscle within and across the various femur regions. Regression analysis was used to evaluate univariate relationships between muscle volume (active and total) and joint torque. When a significant interaction was found, a one-way ANOVA for repeated measures was performed to test for simple effects and then followed, when appropriate, by t-tests for dependent measures. Main effects were only interpreted in the absence of a significant interaction. A Bonferroni correction for multiple comparisons was used when evaluating differences in means. Significance was set a priori at P ≤ 0.05. Power analysis revealed that the sample size of n = 7 was sufficient to detect an interaction effect of 0.9 SD and a main effect of 0.42 SD (36) among T2 MRI-assessed muscle activation (right 100 Hz, right 25 Hz, left 100 Hz, and left 25 Hz) using a completely within-subject repeated-measures ANOVA with an {alpha}-level of 0.05 and a power of 0.8, assuming a correlation between repeated measures of 0.9.

Injury Experiments

Subjects.   Eight men (24 ± 3 yr old), with a height of 182 ± 8 cm and a mass of 72 ± 6 kg, volunteered to participate in this study. Self-reported daily physical activity varied across subjects from recreationally active to sedentary. No subject had performed resistance exercise with their legs during the previous year. All subjects were otherwise healthy with no history of pathology of the lower extremities.

Experimental design.   Subjects performed a series of MVIC with the right and left QF muscle groups to assess maximal voluntary torque production. On a separate day, two bouts of EMS-evoked eccentric exercise of the QF were performed. Subjects were randomly assigned to receive 100-Hz EMS in one thigh and 25-Hz EMS in the other. MR images were acquired at rest (before bouts of EMS) and 72 h after the eccentric exercise bouts. MVIC and ratings of muscle soreness were obtained from each subject on days 1–4, 7, 10, and 14 after the eccentric exercise bout.

Electrically stimulated exercise.   Stimulation electrodes were placed on the right and left thighs of each subject as described in Activation Experiments above. Subjects were randomly assigned to receive 100-Hz EMS in one thigh and 25-Hz EMS in the contralateral thigh. The EMS amplitude needed to evoke 50% of MVIC at a knee angle of 70° below horizontal was determined in the 100-Hz thigh. Once this amplitude and force level were established, the 25-Hz thigh was stimulated at 100 Hz until the amplitude needed to match isometric force production between thighs (at 100 Hz) was determined. EMS frequency was then reduced to 25 Hz for performance of the eccentric contractions. Eight sets of 10 eccentric contractions were subsequently performed at both 100 and 25 Hz via an 80° knee joint range of motion (from 10° to 90° below horizontal) with a contraction velocity of 120°/s on a KinCom isokinetic dynamometer. The dynamometer returned the lever arm to 10° of knee flexion on completion of each eccentric action. A preset torque equal to ~80% of stimulated isometric torque at the start angle (10°) had to be overcome before movement of the lever arm occurred. This ensured sufficient time (~0.5 s) for torque development and removal of muscle compliance. Peak eccentric torque during each set was recorded for future analysis.

MRIs.   T2 MR images were collected before and on day 3 after the exercise bout. MRIs were performed essentially as described above in Activation Experiments. The percentage of the total QF volume demonstrating an increase in T2 signal intensity was calculated by comparing the images collected before exercise with those collected 72 h after eccentric exercise as done previously (7). The delayed increase in T2 after eccentric exercise has been shown to persist for several days or weeks (12, 38). In the present study, imaging was performed 72 h postexercise because we felt this time point allows sufficient time for T2 elevation and corresponds well to the time course of changes in other markers of muscle injury such as swelling, soreness, and isometric force loss. The volume of muscle demonstrating an increase in T2 (VDI T2) was calculated, on a pixel-by-pixel basis, using the same criteria described previously for the activation experiment. In addition, the change in the mean T2 signal intensity of the entire QF was calculated as the difference between the mean T2 of the entire QF muscle group (averaged across all slices) in resting images and posteccentric exercise images. Percent change in muscle volume (swelling) was calculated as the change in total volume of the QF muscle group from resting to postexercise images. On the basis of findings from experiment 1, the volume of injured muscle was separated into 15 regions each representing 1/15 of Lf to examine the spatial location of injured muscle in the QF.

Assessment of MVIC.   Isometric knee extension was performed as described previously (7) and as described above in Activation Experiments.

Muscle soreness.   Muscle soreness was assessed with the use of a 100-mm visual analog scale before and on days 1–4, 7, 10, and 14 after eccentric exercise of the right and left QF. The scale was anchored, with "0" representing a complete lack of soreness and "100" representing the worst soreness imaginable.

Ratings were made after voluntary concentric and eccentric contractions of the knee extensors; these contractions moved the leg from 90° below horizontal to full extension and then back to 90° below horizontal at a velocity of 45°/s with a load equal to 10% of each subject's MVIC. Subjects were instructed to rate their pain during the eccentric portion of the lift.

Statistical analysis.   Results are expressed as means ± SD. Dependent sample t-tests were conducted to compare differences in percentage of muscle considered injured, change in mean T2, and percent swelling between the 100 and 25 Hz thighs. A two-factor specific torque (100 and 25 Hz) x contraction number, specific torque (100 and 25 Hz) x time (days after exercise), or specific torque (100 Hz and 25 Hz) x Lf region (regions 1–15) within-subject ANOVA was conducted to determine differences in eccentric contraction force during each exercise bout, voluntary torque loss, and perceived soreness. When a significant interaction was found, a one-way ANOVA for repeated measures was performed to test for simple effects and then followed, when appropriate, by t-tests for dependent measures. Main effects were only interpreted in the absence of a significant interaction. A Bonferroni correction for multiple comparisons was used when evaluating differences in means. Significance was set a priori at P ≤ 0.05. Power analysis revealed that the sample size of n = 8 was sufficient to detect an interaction effect of 0.94 SD and a main effect of 0.30 SD (36) with regard to change in isometric strength and muscle soreness using a repeated-measures ANOVA and an effect of 0.53 SD using a paired t-test to evaluate the mean change in T2 signal intensity, volume of the QF demonstrating an increase in T2, and change in QF volume, change in muscle volume with a {alpha}-level of 0.05, and a power of 0.8, assuming a correlation between repeated measures of 0.9.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Activation Experiments

Isometric exercise.   MVIC of the QF muscle group and isometric torque evoked by 25- and 100-Hz EMS are shown in Table 1. A significant main effect for exercise type was found (P = 0.002) with torque from MVIC >100-Hz EMS > 25-Hz EMS (P < 0.016 for each). No differences in voluntary or evoked torque were observed between the right and left thighs. Torque evoked by 25-Hz stimulation was, on average, 38% of MVIC, whereas torque evoked by 100-Hz stimulation was 51% of MVIC. Stimulation amplitude used to evoke contractions ranged from 41 to 70 mA and from 43 to 70 mA for the right and left thighs, respectively, with no differences observed in the means (57 ± 11 vs. 58 ± 11). The 100-Hz EMS yielded higher specific torque values than the 25-Hz EMS (Table 1; P ≤ 0.002), with estimates from 25-Hz EMS being, on average, 0.04 N·m/cm3 (20%) lower than those from 100-Hz EMS. No differences in specific torque were observed between the right and left thighs (P = 0.20).


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  		Table 1. Measured and calculated values during voluntary and electrically evoked contractions

 
MRI.   Total QF muscle volume was 8% (P = 0.009) smaller in the left thigh than in the right (Table 1). After EMS-evoked isometric exercise, a similar amount of muscle was activated both within and between the right and left QF at 25 Hz and 100 Hz (Table 1). Total QF muscle volume was found to be linearly related to MVIC (r2 of 0.94 and 0.86 for the right and left thighs, respectively; P < 0.05). In addition, a linear relationship was also found between activated muscle volume and torque evoked by 25- and 100-Hz EMS (r2 from 0.85 to 0.91, P ≤ 0.007). Figure 1 shows representative T2 maps of activated muscle in distal, midthigh, and proximal cross-sections before EMS and in response to 100- and 25-Hz EMS. Although differences were noted between subjects with regard to the amount and location of active muscle, altering EMS frequency yielded qualitatively similar T2 maps for a given subject. The percentage of total muscle activated within a given femur region can be seen in Fig. 2. A significant thigh x region interaction was found (P = 0.009), but 100- and 25-Hz EMS activated a similar amount of muscle within the right or left thigh. In general, active muscle was greatest in the distal regions (Lf regions 1–4) and decreased progressively, moving proximally along the femur with active muscle being significantly reduced from region 1 in regions 12–15 and 11–15 in the right and left thighs, respectively (Fig. 2, B and C; P < 0.05). When summed across all regions, activated muscle was not different between the right and left QF (Table 1). However, the location of the activated muscle was found to differ between the right and left thigh in the most proximal regions (regions 13–15; P ≤ 0.05).


Figure 1
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  		Fig. 1. A: representative coronal image of the thigh, with each gridline indicating the approximate location of each region of femur length (Lf). B: representative, anatomically matched axial transverse relaxation time (T2) magnetic resonance images from the distal (region 3), midthigh (region 9), and proximal (region 14) areas of quadriceps femoris (QF) before electromyostimulation (EMS) (native) and after 100- and 25-Hz EMS from the left thigh of a subject. Activated muscle is shown in black. Note that activated muscle can be found throughout (deep and superficial) the QF and that a similar pattern (amount and location) of activated muscle occurs within each image at 100 and 25 Hz. VM, vastus medialis; VL, vastus lateralis; RF, rectus femoris; VI, vastus intermedius.

 

Figure 2
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  		Fig. 2. Percent QF muscle volume considered active within a given region of Lf after 100- and 25-Hz EMS. A: right (Rt) and left thighs. For sake of clarity, error bars not shown. *P < 0.05, between 100- and 25-Hz bouts. B: 100- and 25-Hz data for the right QF. C: 100- and 25-Hz data for the left QF. §P < 0.05, percent active muscle different from region 1.

 
Injury Experiments

Eccentric exercise.   Peak eccentric contraction torque evoked during 100-Hz EMS was 75% greater than that evoked during 25-Hz EMS (Fig. 3). Eccentric torque was significantly different between the 100- and 25-Hz bouts over the course of the initial 10 contractions (P ≤ 0.05; Fig. 3). Torque declined to a greater extent over 80 contractions in the 100-Hz thigh than in the 25-Hz thigh (69 ± 11% vs. 47 ± 13%, P = 0.0002).


Figure 3
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  		Fig. 3. Change in eccentric torque during 80 eccentric contractions evoked at 100 and 25 Hz. *P < 0.05, between 100- and 25-Hz bouts.

 
MRI.   Representative T2 MR images from resting (before exercise) and delayed (3 days postexercise) conditions are presented in Fig. 4. Eccentric exercise evoked at a high specific torque (100 Hz) induced a T2 contrast shift in a significantly larger percentage of the total volume of the QF than that evoked at 25-Hz EMS (Table 2). Indeed, little if any of the volume of the QF demonstrated an increase in T2 after the 25-Hz bout. In addition, the 100-Hz thigh exhibited a marked increase in QF muscle volume (swelling) and in mean T2 signal intensity, whereas little change in either variable was observed in the 25-Hz thigh (Table 2). When the VDI T2 was examined within a given femur region (as performed in experiment 1 for muscle activation), peak VDI T2 was found in region 7 (36 ± 26%) and region 3 (6 ± 10%) for the 100- and 25-Hz thighs, respectively (Fig. 5). A significant thigh-by-region interaction (P < 0.05) was found, and one-way ANOVA indicated that only the most proximal regions (Lf regions 13–15; P < 0.05) had significantly reduced VDI T2 compared with region 7, where the largest VDI occurred, in the 100-Hz thigh. In the 25-Hz thigh, VDI T2 was similar across all regions.


Figure 4
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  		Fig. 4. Representative, anatomically matched axial T2 magnetic resonance images from the midthigh region of the QF before (A) and 72 h after (B) eccentric exercise at 100 and 25 Hz. C: binary map of muscle demonstrating an increase in T2 (indicated in black).

 

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  		Table 2. MRI-assessed indexes of muscle injury

 

Figure 5
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  		Fig. 5. Percent QF muscle volume demonstrating an increase in T2 intensity (VDI T2) within a given region of Lf after eccentric exercise at 100 and 25 Hz. §P < 0.05, VDI T2 in Lf region different from Lf region, demonstrating the largest VDI T2 (regions 7 and 3 for 100- and 25-Hz bouts, respectively).

 
Isomeric torque loss.   Changes in maximal voluntary isometric force are shown in Fig. 6A. A significant thigh-by-day interaction was found (P = 0.039) with subsequent analysis demonstrating that, after exercise at 100 Hz, MVIC was reduced compared with baseline levels immediately postexercise, on days 1–4 and 7 (P < 0.001), with the peak decline (39%) occurring 2 days after the eccentric exercise bout. The peak reduction (14%, P = 0.011) in MVIC after 25-Hz exercise occurred immediately postexercise, with this time point being the only one that differed from baseline values for MVIC.


Figure 6
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  		Fig. 6. Change in maximal voluntary isometric contractions (MVIC; A) and muscle soreness (B) over 14 days after eccentric exercise at 100 and 25 Hz. *P < 0.05, between peak decline in MVIC (day 2 vs. immediately postexercise) and peak soreness (day 2 vs. immediately postexercise) between the 100- and 25-Hz bouts. §P < 0.05, decrease in MVIC and increase in soreness from preexercise levels.

 
Muscle soreness.   Ratings of muscle soreness are shown in Fig. 6B. A significant thigh-by-day interaction was found (P = 0.008). Soreness peaked 2 days postexercise and immediately postexercise in the 100- and 25-Hz thighs, respectively. In the 100-Hz thigh, ratings of soreness differed from baseline from immediately postexercise to 4 days postexercise (P < 0.05), whereas soreness differed from baseline only immediately postexercise and on day 1 (P < 0.05) after 25-Hz exercise. Significantly greater soreness was observed after the 100-Hz bout, relative to the 25-Hz bout, immediately posteccentric exercise and on days 1–4 (P < 0.05).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The purpose of the present study was to determine the role that specific torque plays in exercise-induced skeletal muscle injury in humans. We tested the hypothesis that, when contraction velocity, range of motion, active muscle, and contraction number were closely matched, electrically stimulated eccentric contractions performed at 100 Hz would result in greater injury than contractions performed at 25 Hz. Markedly greater changes were found in all measures of muscle injury after the 100-Hz bout. These findings agree with those from animal studies (19, 27), implicating high specific torque or stress as the initiating event in exercise-induced injury. The data are also consistent with the idea that eccentric actions cause greater injury than isometric or concentric actions because they activate less muscle to generate a given level of force (4, 5).

Peak eccentric torque was ~75% greater during the 100-Hz bout and remained elevated compared with the 25-Hz bout across the first 10 (of 80) contractions. Assuming similar muscle activation between the bouts, individual muscle fibers activated during the 100-Hz bout experienced a greater specific torque, especially over the first 10 contractions, than those activated during the 25-Hz bout. The 100-Hz bout induced a greater decline in isometric force (39% vs. 14%), greater ratings of muscle soreness (40 vs. 13 mm), a greater relative volume of the QF demonstrating an increase in T2 (28% vs. 0.5%), a greater mean change in T2 of the QF (4.3 vs. 0.0 ms), and a greater change in QF muscle volume (9% vs. 1%) than shown with the 25-Hz bout. Together, these findings suggest the higher specific torque of the 100-Hz bout, especially during the initial 10 contractions, resulted in greater muscle injury. These finding contrast with previous reports from animal models suggesting that contraction velocity (8, 45) and strain (8, 23) are the most important factors in initiating muscle injury and contrast with human studies implicating initial muscle length (29). Our findings are strengthened by the fact that high muscle forces, which because of complete activation of the muscle is essentially a surrogate of specific force/torque, have been shown to play a role in injury in animals (19, 27, 45). The idea that high force per active area of muscle is an important determinant in exercise-induced injury is mechanistically consistent with two other widely held ideas. 1) Decreased motor unit recruitment at any given force level, leading to higher force per active area, is why muscle injury tends to occur in response to eccentric but not isometric or concentric muscle actions (4, 5, 27). 2) A "neural" adaptation underlies the protective or repeated-bout effect. If additional motor units could be recruited or if motor units could be recruited in a more synchronous manner to lift a given weight, as has been suggested by others (28), it would effectively lower specific torque during subsequent bouts of exercise. Our results suggest the dramatic reduction in injury that could result from an adaptation of this type.

As outlined by Warren et al. (46), the normal stress theory mechanism of failure states that the weakest contractile or series component of a muscle will fail when a tensile stress, exceeding its yield strength, is applied. During muscle contractions in vivo,specific force likely represents the best measure of tensile stress. In accordance with this theory, the idea of a force threshold for the initiation of muscle injury has been proposed by others (17, 43), and data indicate that contraction forces approaching 115–120% of those produced during maximal isometric contractions may provide sufficient tensile stress to exceed the yield strength of a muscle fiber (43, 45). In the present study, peak eccentric torque during 100-Hz EMS was, on average, 123% of MVIC, whereas peak torque during 25-Hz EMS was only 73% of MVIC (data not shown). The amount of EMS applied in the present study likely activated only 40–50% of the QF during each bout. Together, these data demonstrate that very high levels of tensile stress, well over those proposed to exceed the yield strength of a muscle fiber, were applied to the fibers of the QF during the 100-Hz bout. An interesting finding, in light of high tensile stress of the 100-Hz bout, was that not all of the fibers activated at 100 Hz were injured, suggesting that a portion of the fiber population was resistant to injury. Several studies have indicated that fast-contracting fibers or motor units may be more vulnerable to injury (3, 14, 44) than their slow-contracting counterparts. Reduced structural proteins, especially in the Z disk (13), lower contractile workload (44), and an ability to generate higher tensions (3) have been proposed as mechanisms underlying the increased vulnerability of fast-twitch fibers. On the basis of the force-frequency relationship for each fiber type, 25-Hz stimulation should evoke a nearly maximal force from slow fibers (22). Increasing EMS frequency to 100 Hz would therefore yield little additional force. Conversely, increasing stimulation frequency from 25 to 100 Hz would likely lead to substantial force augmentation in fast-twitch fibers (22). The observed difference in injury between the bouts are consistent with the idea that moving from 25 to 100 Hz EMS increased the tensile stress, such that it exceeded the yield strength, of the more vulnerable fast-twitch fibers. In the present study, considerable intersubject variation was found in our measures of injury. A recent study by Hubal et al. (20) also reported large variations in muscle injury, assessed by isometric force loss after eccentric exercise, and classified subjects as high responders, low responders, or nonresponders. The large variation observed in the present study should be expected given the potential differences in fiber-type percentages, loading history, pain tolerance and history, immune responses, and other genetic factors between subjects.

It is unclear, especially in humans, whether a single, high-stress eccentric contraction is sufficient to induce injury or whether injury occurs in a cumulative manner over multiple high-stress contractions. The concept that multiple contractions induce "materials fatigue" within muscle fibers was put forth by Warren et al. (46) and is supported by both animal (27, 42, 46) and human (9) data indicating that increasing the number of eccentric contractions increases muscle injury. The large and steady declines in eccentric torque during the first 10 contractions of the 100-Hz exercise bout (Fig. 3) likely represent the progressive increases in muscle damage, rather than fatigue, across these contractions, suggesting that the high tensile stress imposed on the muscle during these initial contractions induced injury in a cumulative manner consistent with materials fatigue. Because eccentric torque, and thus specific torque, did not differ between bouts over the final 70 contractions, it appears that almost all of the injury occurred during the initial 10 contractions. Indeed, it seems likely that if only 10 contractions had been performed at 100 Hz similar injury would have resulted.

Debate remains as to the site of muscle injury. It has been suggested that failure may occur in force-transmitting structures external to muscle fibers such as the myotendinous junction (43) and the extracellular matrix (41) or within the contractile elements of fibers (5, 27). It is not possible to determine the structure that failed on the basis of data from the present study. However, our finding that muscle was injured in a roughly uniform manner across the mid and distal Lf regions (Fig. 5) agrees with histological data demonstrating sarcomere disruption throughout the belly of the muscle (45) and suggests that muscle injury was not solely localized around the myotendinous junction.

It is well documented that eccentrically exercised muscles demonstrate a delayed increase in T2 that peaks several days after exercise and persists for several weeks (12, 39). Debate remains as to the mechanism responsible for this prolonged increase in relaxation time that persists long after other markers of injury have returned to baseline levels. The initial delayed response, occurring during the first week, has been shown correlate with histological assessment of muscle injury in both humans (30) and animals (26) and follows a similar time course to traditional markers of muscle injury such as soreness, serum creatine kinase levels, swelling, and force loss (7, 12, 38). It has been suggested that this initial response tracks transient damage to the muscle and may potentially be associated with edema (32), whereas the prolonged elevation of T2 likely reflects a long-lasting adaptation (12). MRI is especially useful for studying muscle injury in vivo because it is noninvasive and allows for spatial localization of injury to individual muscles. The pixel-by-pixel analysis employed in the present study has been used in several previous studies (6, 7, 31, 34, 35, 40) and is thought to provide a quantitative index of the relative extent and pattern of muscle injury (31). This method has not been validated against histological assessment of muscle damage, and data are not available regarding the relationship between the relative area demonstrating an increase in T2 and other indirect markers of injury (likely because of small sample sizes). Nevertheless, data from previous studies (6, 7, 31, 34, 35, 40) are consistent with our finding that, as the area with an elevated T2 increases, concurrent increases are observed in strength loss, swelling, and soreness. Further studies are needed to determine the mechanism(s) underlying the delayed increase in T2 signal intensity and to compare the pixel-by-pixel analysis with ultrastructural changes consistent with muscle injury.

From an experimental design standpoint, it was of great importance to match the amount of muscle activated during each bout of eccentric exercise as closely as possible. Because of methodological limitations, we were unable to quantify activation during the eccentric exercise protocol. Consequently, a separate experiment was performed under isometric conditions to provide data regarding muscle activation during EMS. It was unclear whether, with a similar electrode placement, muscle activated by EMS could be matched between the right and left QF if external torque (evoked at the same EMS frequency) was also matched between thighs. Our data provide in vivo evidence that matching external torque between the right and left QF does indeed yield similar volumes of active muscle. In addition, active muscle remained similar both within and between thighs when EMS frequency was lowered from 100 to 25 Hz without alteration of stimulation amplitude (Table 1). These data confirmed previous findings (16) that specific forces during EMS are controlled by frequency, whereas EMS amplitude controls the amount of muscle activated during contractions (2). This novel finding provides the first confirmation in humans that torque production can be experimentally manipulated between a subject's limbs, by altering EMS frequency, while holding active muscle mass constant, a condition that does not occur during voluntary actions. When calculated with EMS-evoked isometric torque and active muscle, specific torque from 100- and 25-Hz EMS was found to be 0.20 and 0.16 N·m/cm3, respectively. These values approximate those reported previously during maximal voluntary actions (15) and indicate that altering the frequency of EMS alters the tensile stress placed on the contracting muscle fibers.

In addition to providing a manipulation check for the experimental design of the injury experiment, the activation experiment also provided data regarding the location of active muscle in the QF. As seen in Fig. 3, active muscle was found in all 15 Lf regions in both the right and left QF after each isometric exercise bout. Although a similar amount of muscle was activated between the right and left QF, the location of active muscle differed between thighs (Fig. 2A). Although qualitatively different in the midthigh regions (Lf regions 4–7), active muscle was only found to be statistically different between the right and left QF in most proximal regions (Lf regions 13–15). If only the midthigh or central regions (Lf regions 4–10) were considered, as done in previous studies (18), one would spuriously conclude that, in the left QF, a smaller portion (12% and 11% for 100 and 25 Hz EMS, respectively; data not shown) was activated to produce a torque similar to that evoked in the right QF. In addition, if specific torque was calculated using only the volume of active muscle from the midthigh regions, values for isometric specific torque would rise to 0.35 and 0.27 N·m/cm3 for 100- and 25-Hz EMS, respectively. By excluding roughly 40% of the muscle activated during EMS, specific torque increases to levels that are well in excess of those reported previously (15). We believe these finding highlight the need to include images that span the entire length of the femur when assessing active muscle of the QF muscle group after EMS. It would be interesting to see whether similar differences in the location and amount of active muscle exist between the right and left QF during voluntary muscle actions. Imaging of this type could potentially be used to track changes in recruitment that occur with training/detraining or due to some type of neuromuscular disease such as Parkinson's or multiple sclerosis.

In summary, when EMS was used to manipulate torque and control active muscle, high specific torque eccentric contractions were found to induce greater changes in markers of muscle injury than those evoked at a lower specific torque. We believe these are novel findings in humans that further implicate the role of high tensile stress, not simply high muscle forces, in the initiation of skeletal muscle injury.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
This research was supported by National Institute of Child Health and Human Development Grants HD-39676 and HD-39676S2 to G. A. Dudley.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
The authors thank the subjects for volunteering for the study. We also thank Carolyn Sharp for technical assistance, Shepherd Center for use of their MRI facilities, and Dr. Jill Slade and Dr. Scott Bickel for critical review of this manuscript.


   FOOTNOTES
 

Address for reprint requests and other correspondence: C. D. Black, Dept. of Kinesiology, The Univ. of Georgia, 330 River Rd. 30602-6554, Athens, GA (e-mail: blackcd{at}uga.edu)

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. Section 1734 solely to indicate this fact.

{dagger} Deceased 30 September 2006. Back


   REFERENCES
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

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