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J Appl Physiol 99: 593-602, 2005. First published March 24, 2005; doi:10.1152/japplphysiol.01128.2004
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Quantification of muscle fiber strain during in vivo repetitive stretch-shortening cycles

Timothy A. Butterfield and Walter Herzog

Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada

Submitted 7 October 2004 ; accepted in final form 21 March 2005


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 APPENDIX
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Muscles subjected to lengthening contractions exhibit evidence of subcellular disruption, arguably a result of fiber strain magnitude. Due to the difficulty associated with measuring fiber strains during lengthening contractions, fiber length estimates have been used to formulate relationships between the magnitude of injury and mechanical measures such as fiber strain. In such protocols, the series compliance is typically minimized by removing the distal tendon and/or preactivating the muscle. These in vitro and in situ experiments do not represent physiological contractions well where fiber strain and muscle strain may be disassociated; thus the mechanisms of in vivo muscle injury remain elusive. The purpose of this paper was to quantify fiber strains during lengthening contractions in vivo and assess the potential role of fiber strain in muscle injury following repetitive stretch-shortening cycles. Using intact New Zealand White rabbit dorsiflexors, fiber strain and joint torque were measured during 50 stretch-shortening cycles. We were able to show that fiber length changes are disassociated from muscle tendon unit length changes and that complex fiber dynamics during these cycles prevent easy estimates of fiber strains. In addition, fiber strains vary, depending on how they are defined, and vary from repetition to repetition, thereby further complicating the potential relationship between muscle injury and fiber strain. We conclude from this study that, during in vivo stretch-shortening cycles, the relationship between fiber strain and muscle injury is complex. This is due, in part, to temporal effects of repeated loading on fiber strain magnitude that may be explained by an increasing compliance of the contractile element as exercise progresses.

skeletal muscle; muscle mechanics; eccentric contraction; force-length relationship; muscle injury; series elastic component; contractile element

LENGTHENING CONTRACTIONS, commonly referred to as eccentric contractions, have been shown to produce fiber injury in vitro (3, 4, 9, 28, 44, 59, 61, 62, 69), in situ (7, 9, 10, 35, 38), and in vivo (2, 17, 20, 22, 23, 50, 54, 56, 57). In vitro and in situ protocols utilize a single stretch (9, 10) or a series of ramp stretches (28, 38, 42, 59, 64) to provide insight into the mechanical properties of skeletal muscle during lengthening contractions and the factors that contribute to muscle injury. Conversely, in vivo protocols involve muscle activation and stretch through a physiological range of motion and, therefore, were found to require more than one repetition to cause measurable muscle injury (14, 61, 66, 67). Although each preparation has it merits, the obvious benefits of in vivo protocols include the preservation of normal muscle-tendon unit (MTU) mechanics and its action around the joint axis.

In vitro and in situ models also differ significantly in how they are prepared. Whereas in vitro procedures include the removal of the distal tendon structures, the vast majority of in situ protocols do not, and therefore incorporate a passive element in series with the contractile element (CE), similar to in vivo protocols. This intact MTU has a greater compliance compared with in vitro preparations, which may serve to complicate measures and estimations of variables associated with muscle injury. The removal of the distal tendon during in vitro procedures reduces the confounding effects of compliance within the system and ensures that most of the stretch is taken up within the contractile portion of the muscle to effectively damage the fibers (5, 6, 10, 14, 28, 59, 64, 68). In addition, in vitro approaches facilitate the estimation of fiber strains based on measured MTU strains, from a starting length (Lo) of the active muscle (9, 10, 35, 36, 58). Because fiber strains have been proposed to be an important factor in predicting muscle injury (38), fiber strain estimates, based on one-to-one relationships with measured MTU strains, have allowed researchers to formulate associations between the magnitude of fiber strain and MTU injury (9–11, 14, 44, 46, 66–68).

Due to the MTU contraction dynamics in vivo, the assumption that fiber length changes mirror MTU length changes may not be valid (70). It has been shown that fiber dynamics are often disassociated (distinct and independent) from MTU dynamics in situ (33) and in vivo (29) so that fibers may shorten as the MTU is lengthened and vice versa. Several researchers have utilized more physiological or in vivo protocols and produced subcellular injury following lengthening contractions with an intact distal tendon, thereby maintaining not only the series arrangement of CE and series elastic component (SEC) but also the natural compliance of the system (5, 6, 14, 21, 40, 41, 51, 52). These studies have reported subcellular injury similar to that seen with single stretches of in situ models, and they may represent a better approach to gain insight into muscle injury for physiologically relevant situations. However, estimates of in vivo fiber strains in the past were made assuming that Lo remains constant and that fiber dynamics mimic MTU dynamics. These are assumptions that do not necessarily hold in vivo (29, 70).

In an effort to increase muscle force production and minimize disassociation of fiber and MTU length changes, most researchers increase the tension of the MTU by applying activation of the muscle before stretch (5, 6, 11, 25, 28, 34, 46, 59, 67, 69). Because tendon lengths (SEC) and fiber lengths (CE) vary from one muscle to another and within a given preparation, the duration of the preactivation (muscle activation preceding muscle length change) may not take up all of the slack in the tendon and allow the fibers to accommodate the increasing length of the MTU if preactivation is too short. This may have an effect on in situ preparations in particular, where the amount of tendon between the muscle contractile component and servomotor is never reported (70) but influences the compliance of the MTU. In addition, unlike in vitro and in situ protocols, preactivation and force are often minimal before MTU lengthening in vivo, such as occurs during locomotion (8, 15, 18, 19, 29, 33). In vivo, increasing force is often associated with increasing MTU length and decreasing force with decreasing length (60). Increasing force tends to shorten muscle fibers, and MTU lengthening tends to stretch them (55), thereby providing competing stimuli to the muscle fibers and making fiber strain estimates virtually impossible.

Therefore, the etiology of muscle injury at the fiber level during lengthening contractions in vivo has eluded convincing explanation. With the distal tendon intact, multiple repetitions are required to produce injury when working through a physiological range of motion (14, 61, 66, 67). This further illustrates the complexity of MTU contraction dynamics and the potential effects of altered MTU compliance with time. The relationship between fiber and MTU strain is likely to vary across repetitions of stretch-shortening cycles because of the known viscoelastic properties of skeletal muscle and fatigue-related decreases in force (24, 30, 45). Furthermore, the rate of decay of eccentric force production, during repeated stretch-shortening cycles in vivo, was found to be a valid indicator of muscle damage (25), although fiber strains were not directly measured in that study. This result further illustrates that the measurement of real-time function of skeletal muscle during repetitive stretch-shortening cycles may prove beneficial to understanding the etiology of strain-induced muscle injury. Therefore, the purpose of this study was to recreate the paradox of shortening muscle fibers and lengthening MTU during an intact, in vivo cyclic, active-lengthening and passive-shortening protocol and to assess the potential relationship between fiber strains in vivo and muscle injury.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 APPENDIX
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Surgical procedure.   Muscle and fiber strains were determined from both hindlimbs (n = 11) of six skeletally mature female New Zealand White (NZW) rabbits (5.3 ± 0.4 kg, Riemens, St. Agatha, ON). Rabbits were tranquilized with 0.18 ml (10 mg/ml) acepro-25 (MTC Pharmaceuticals, Cambridge, ON) and held under anesthesia with 1.5% isoflourane, 0.6 l/min N2O, and 0.8 l/min O2. Incisions were made on the posterior aspect of the hindlimbs, anterior to the sciatic vein, and the biceps femoris and semimembranosus were separated, exposing the peroneal nerve. Nerve cuff stimulating electrodes were secured over the right and left common peroneal nerves, superior to the gastrocnemius and distal to the branching of the sciatic nerve. In this manner, all dorsiflexors of the tibiotarsal joints were stimulated effectively.

To measure fascicle lengths, an incision was made over the anterior aspect of the shank, exposing the tibialis anterior (TA) and extensor digitorum longus (EDL). The fascia was removed from the anterior aspect of the TA, and a central, superficial fascicle was isolated using microstimulation (29). A 32-gauge needle tipped with methylene blue dye was used to mark the proximal and distal ends of the fascicle, and a small incision was made to insert a 2-mm piezoelectric crystal at these locations (Sonometric, London, ON). The crystals were then secured using small 5–0 silk sutures. Once the crystals were securely implanted, the skin was sutured closed. All procedures were approved by the Animal Care Committee of the University of Calgary.

Fiber strain measurements.   Rabbits were placed supine in a stereotaxic frame with the knee joint at 90°. The left foot was strapped to a servomotor foot plate (Parker Hannifin, Irwin, PA) that was controlled via computer (Motion Planner, Rohnert Park, CA). The tibiotarsal angle was set at 90° (increased tibiotarsal joint angle = increased plantar flexion), which served as the reference angle for the remainder of the experiment. The peroneal nerve cuff leads were attached to a stimulator (Grass S8800, Astro-Med, Longueil, PQ), and the {alpha}-motoneuron threshold was determined (pulse duration = 0.1 ms, frequency = 150 Hz, train duration = 500 ms).

First, a preexercise, isometric force-length relationship was determined by supramaximally stimulating [3x {alpha}-motoneuron threshold voltage (range = 1.2–3.0 V), pulse duration = 0.1 ms, frequency = 150 Hz, train duration = 2,000 ms] the dorsiflexor muscles, beginning at a tibiotarsal angle of 55° and progressing in 5° increments to 155°. The foot was returned to a dorsiflexed position (55° tibiotarsal angle) for 2 min of rest between contractions. Then eccentric contractions were performed from a tibiotarsal angle of 70–105° of plantar flexion at 70°/s. Tibiotarsal torque was measured from strain gauges placed on the cam between the servomotor and footplate. Stimulation started and ceased at the beginning and the end of the eccentric exercise, respectively. The protocol consisted of five sets of 10 eccentric contractions, with 2-min rest between sets. Immediately after the eccentric protocol, a postexercise torque-joint angle relationship was measured in a manner identical to the preexercise relationship. However, the rest between isometric contractions was reduced to 30 s to limit the recovery from fatigue during measurement of the force-length relationship postexercise. Therefore, the foot was returned to a dorsiflexed position (55° tibiotarsal joint angle) between contractions but for <30 s of rest before moving to the next joint angle. The postexercise torque-length relationship was measured by plotting the 21 torque values with respect to joint angle. Values >75% of the peak torque were identified and normalized with respect to peak torque. These values were then fit with a second-order polynomial, and the angle of peak torque production was calculated using a polynomial approximation, as suggested in the literature (31, 65).

All data were collected via Sonosoft data-acquisition systems (Sonometrics, London, ON) at 498 samples/s. Torque signals were low-pass filtered at 20 Hz through a second-order recursive Butterworth filter (Intertechnology, Don Mills, ON). Fiber lengths during the entire protocol were measured using sonomicrometry for the two piezeoelectric crystals inserted in the central, superficial fascicle (13, 29). Because fibers of the TA do not run the entire length of the muscle (37), we measured fascicle length. Thus the term "fiber" in this paper refers to fascicles that span the entire length of the TA from the distal to the proximal aponeurosis. Percent fiber strain was calculated using Eq. 1,

(1)
where T is the instantaneous ultrasound transmission time between the two crystals, and To is the ultrasound transmission time at the muscle fiber reference length (70° tibiotarsal joint angle, just before starting the MTU stretch and activation). MTU length change was determined by using a tendon travel approach (1) after death.

Due to the complex fiber dynamics during eccentric contractions, fiber strains were defined during the stretch-shortening cycles with respect to Fig. 1. Negative strains were defined as shortening, and the subscript r refers to repetition number. 1) Active shortening is the period of fiber shortening at the onset of MTU stretch as force is increasing (Br – Ar) or the difference between the shortest fiber length measured during activation (Br) and the fiber length immediately before activation (Ar). 2) Active strain is the period of fiber stretch during the eccentric MTU phase (Cr – Br) or the difference between the longest (Cr) and the shortest (Br) fiber lengths measured during activation. 3) Relaxation strain is the period of fiber stretch at the beginning of passive MTU shortening when muscle force is decreasing (Dr – Cr). Relaxation strain represents the difference between the peak fiber length achieved during muscle relaxation (Dr) and the peak fiber length during active stretch (Cr). 4) Passive shortening is the period of fiber shortening during passive MTU shortening (Ar+1 – Dr) when force is zero. This is the difference from the fiber length immediately before activation for the next stretch-shorten cycle (Ar+1) and the peak fiber length during relaxation (Dr). 5) Repetitionr strain is the fiber strain calculated from (Dr – Ar) for each repetition, where Ar is the fiber length before activation of each cycle, and Dr is the peak fiber length during each cycle (which always occurred during muscle relaxation). 6) Repetition strain differs from net strain, in that repetition strain is measured from the fiber length preceding each stretch-shortening cycle (Ar), whereas net strain is calculated from the fiber length preceding the first stretch-shortening cycle (A1 or Lo). 7) Lastly, maximum strain was calculated as the shortest fiber length (Br) subtracted from the longest fiber length (Dr) during each repetition (Fig. 1, Dr – Br) and included both active and relaxation strains.



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  		Fig. 1. Representative raw data trace of repetition 1 showing the 4 phases of fiber strain during 1 muscle-tendon unit (MTU) stretch-shorten cycle. Subscript r represents eccentric-concentric repetition number. A1 represents the starting length (Lo) of the fibers before eccentric contractions. Point Br represents the shortest length of the fiber following the active shortening (Ar to Br) during the eccentric contraction. Active stretch is defined as the change of fiber length during the eccentric phase from Br to Cr (Cr – Br). During the concentric, deactivated phase, the relaxation strain occurs from point Cr to point Dr, and the corresponding length change is calculated by (Dr – Cr). Following the relaxation strain, the fibers shorten as the MTU continues to shorten during the return of the foot to the initial, dorsiflexed position and to point Ar of the next repetition, point Ar+1. Down arrows indicate start of activation. TA, tibialis anterior.

 
Statistical analysis.   All statistical analyses were performed using SPSS version 12.0 (SPSS, Chicago, IL). For all parameters measured, mean and SE are reported. Statistical significance was set at P < 0.05, and all measurements of fiber strains were analyzed using a two-way analysis of variance. Repeated-measures analysis of variance was used to assess significant changes in strain with time within each set. To evaluate the relationships between various types of strain, multiple one-variable linear regressions were used. Nonparametric tests were used to assess the change in slopes of the torque-strain relationships, and Student’s paired t-tests were used to assess the shift in the torque-angle relationship, torque decrements during stretch, and optimal fiber lengths pre- and postexercise.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 APPENDIX
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
MTU and fiber strain.   During the MTU stretch-shortening protocol, muscles were stretched from 106.2 ± 2.9 to 111.5 ± 3.1 mm, for a net strain of 5.0 ± 0.2%, and then shortened back to the Lo for each cycle. During the active-lengthening phase of the MTU (Fig. 1), fibers first shortened on activation and force production (Fig. 1, Ar to Br), which we defined as active fiber shortening. Values for active fiber shortening ranged from –12.4 ± 0.8% for set 1, repetition 1, to –5.6 ± 0.3% for set 5, repetition 10 (APPENDIX). Mean active shortening was significantly greater in the first set compared with sets 4 and 5 (P = 0.004). A significant interaction of repetition and set (P < 0.001) indicated that mean active fiber shortening significantly decreased with time. Within each set, fibers shortened significantly less with every other repetition in set 1, but over time significant differences between repetitions within each set diminished. Therefore, mean active shortening was greatest during sets 1–3, but significantly decreased with time, partly due to less significant differences between repetitions within each set (Fig. 2). Within each set, torque production diminished with each repetition, as expected due to the effects of fatigue. However, with time, fibers shortened less for a given amount of torque production (Fig. 3). Statistical analysis revealed a significant increase in slope of the torque-active-shortening relationship with time (P = 0.012).



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  		Fig. 2. Mean active fiber shortening (defined as Ar – Br, Fig. 1) for all 50 repetitions. *Note that mean active shortening was significantly greater in set 1 compared with sets 4 and 5. Within each set, repetitions are significantly different than the previous value if it is marked as an "x" in a shaded square. Values are means ± SE; n = 11.

 


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  		Fig. 3. The relationship between contractile element (CE) torque production and CE shortening for 49 repetitions (repetition 1, as an outlier of high torque and shortening magnitude, was removed for clarity) for set 1 ({bullet}), set 2 ({circ}), set 3 ({blacktriangleup}), set 4 ({triangleup}), and set 5 ({blacksquare}). Note, as set number increases, the CE shortens less for a given amount of torque (smaller negative strain).

 
Following the active-shortening phase, fibers were stretched for the remainder of MTU active-lengthening phase (Fig. 1, Br to Cr), defined as active fiber strain (Cr – Br). There was no significant effect of set on active fiber strain, as mean strains per set were not significantly different (P = 1.00). However, active fiber strain was significantly affected by repetition (P < 0.001), with mean strains increasing over time (from 8.1 ± 0.6 to 10.9 ± 0.7% in set 1 and from 8.4 ± 0.5 to 11.0 ± 0.7% in set 5; APPENDIX). Repeated analysis of variance revealed that active strain increased significantly to the eighth repetition in set 1 and to the fifth repetition in set 5 (P < 0.05). Therefore, mean active strain resulted in stretching the fibers to significantly greater lengths late in each set, but this effect diminished with repeat stretch cycles (Fig. 4). Torque production, from repetitions 1–10 within each set, was reduced at both the beginning (Br) and the end of active strain (Cr), with the mean reduction being significantly greater (P < 0.001) at the end (–3.5 ± 0.3%) compared with the beginning (–2.1 ± 0.3%) of active strain.



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  		Fig. 4. Mean active fiber strains (defined as Cr – Br, Fig. 1) for all 50 repetitions. Note that the mean active strain values are not significantly different between sets. Within each set, active strains significantly increase with repetition (shaded square with x) early but become asymptotic later in each set over time. Values are means ± SE; n = 11.

 
During the passive-shortening phase of the MTU, fibers were first stretched on deactivation and diminishing force (Fig. 1, Cr to Dr). This was defined as relaxation strain (Dr – Cr) and resulted in the fibers being stretched to their greatest magnitude during every stretch-shorten cycle (Fig. 1, point Dr). The greatest mean relaxation strain was measured in the first repetition of set 1 (5.3 ± 0.4%), and the smallest value was measured in the final stretch-shortening cycle (0.9 ± 0.1%, set 5, repetition 10, Fig. 5). There was a significant effect of both set (P = 0.018) and repetition (P < 0.001) on relaxation strain. Mean relaxation strain was significantly greater in set 1 compared with set 5 (P = 0.021). Within set 1, relaxation strain decreased significantly for each repetition (P < 0.05), and a similar pattern was seen in the remaining four sets.



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  		Fig. 5. Mean relaxation fiber strains (defined as Dr – Cr, Fig. 1) for all 50 repetitions. *Note, the mean relaxation strain values are significantly less in set 5 compared with set 1. Within each set, relaxation strains significantly decrease with almost every repetition (shaded square with x). Values are means ± SE; n = 11.

 
Fiber lengths and fiber strains relative to A1 (Lo) are shown in the APPENDIX for all MTU stretch-shortening cycles. Fiber strain during the MTU stretch phase (Fig. 1, Cr – Lo) was always negative, indicating that the fibers were shortened, on average, for the entire active-lengthening phase of the MTU. Fibers always reached their greatest lengths during passive MTU shortening (Fig. 1, Dr). Net strains, calculated as Dr – Lo (Fig. 1), remained relatively constant but increased with each set until reaching a peak value of –0.2% (APPENDIX), although this increase was not significant between sets (P = 0.997). Therefore, the peak fiber length reached during each cycle (Dr, Fig. 1) must have remained relatively constant from set to set. Two-way analysis of variance revealed a significant difference within repetitions (P < 0.001), and repeated-measures analysis of repetition within each set revealed a significant decrease in net strain early in sets 1, 3, and 5 (P < 0.05) only, due to the longer fiber lengths achieved during relaxation strain (D, Fig. 1) of the first repetition in each of those sets (APPENDIX). Thereafter, peak fiber lengths, along with net strains, remained relatively constant (Fig. 6).



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  		Fig. 6. Mean net fiber strains (defined as Dr – A1, Fig. 1) for all 50 repetitions. Note, the mean net strain values are not significantly different between sets. Within each set, net strains remain relatively constant over time after set 2 (shaded square with x). Values are means ± SE; n = 11.

 
Following the relaxation strain phase, fibers shortened for the remainder of the MTU shortening phase, defined as passive shortening (Fig. 1, Dr to Ar+1). However, Ar+1 never reached the value of A1 (Lo) again during the course of the exercise. Although we measured net strain based on A1 (Lo), we felt it was necessary to also measure strain based on the fiber length before active shortening for each cycle, as starting and peak fiber lengths (APPENDIX, Ar and Dr, respectively) changed slightly from repetition to repetition. Therefore, we defined repetition strain as (Dr – Ar). Repetition strain was very small for the first repetition (–0.3 ± 2.1%) due to the initial long Lo of the fibers (A1 or Lo = 43.7 ± 5.0 mm, APPENDIX). However, A2 decreased to 41.6 ± 5.1 mm, thereby contributing to an increased repetition strain of +4.8 ± 1.9% for repetition 2. Two-way analysis of variance revealed no significant effect of set on strain magnitude (P = 0.675), indicating that the mean strain of each set did not differ significantly from one set to the next. However, there was a significant effect of repetition (P < 0.001), and a significant interaction of repetition and set (P < 0.001), with repetition strain being significantly less for set 1. This was due to the long starting fiber length before the first repetition (Fig. 7). Further analysis revealed a pattern of significantly increasing repetition strain in set 1 for the first four repetitions (P < 0.05). Although repetition strain was significantly greater for the second compared with the first repetition in each set, the effect of repetition on strain diminished with time, and repetition strains in sets 4 and 5 were similar (Fig. 7).



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  		Fig. 7. Mean repetition fiber strains (defined as Dr – Ar, Fig. 1) for all 50 repetitions. Note, the mean repetition strain values were not significantly different between sets. Within each set, repetition strain significantly increased in the second repetition (shaded square with x) but then did not significantly change during the rest of the set. Values are means ± SE; n = 11.

 
The peak value for maximum strain (Dr – Br, Fig. 1) was 13.9 ± 0.8% and diminished to 12.0 ± 0.8% in repetition 50 (APPENDIX). The maximum strain is the sum of the active (Fig. 1, Cr – Br) and relaxation strains (Fig. 1, Dr – Cr) or simply the strain from the shortest to the longest fiber lengths during one complete stretch-shortening cycle, including fiber length changes in both the activated and deactivated muscle. There was a significant effect of repetition on maximum strain (P < 0.001), but no significant effect of set (P = 0.983). Maximum strain values decreased significantly (P < 0.05) from repetitions 4–6 in set 1, but differences diminished within each set for the rest of the exercise protocol. Within sets 4 and 5, the pattern of maximum strains were similar (Fig. 8).



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  		Fig. 8. Mean maximum fiber strains (defined as Dr – Br, Fig. 1) for all 50 repetitions. Note, the mean maximum strain values were not significantly different between sets. Within each set, maximum strain significantly decreased during the first half of each set (shaded square with x) and then remained constant. Values are means ± SE; n = 11.

 
To determine the dependence of net, repetition, and maximum strain on active shortening, active strain, and relaxation strain, multiple linear regression analysis was used, and the results are displayed in Table 1. Repetition strain is the sum active shortening, active strain, and relaxation strain. Of the three, active shortening is by far the best predictor of repetition strain (r2 = 0.85), whereas active and relaxation strains are only weak predictors (r2 = 0.20 and 0.23, respectively). Specifically, as active shortening decreases over time, repetition strain increases; thus the two are related in an inverse manner. Similarly, maximum strain can be considered as the sum of active strain and relaxation strain. Although both are good predictors of maximum strain, relaxation strain is the better predictor (r2 = 0.77 compared with r2 = 0.54).


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  		Table 1. Multiple linear regression analysis to illustrate the relationships between strains

 
Torque-angle relationships.   The fiber length at peak torque production following eccentric exercise was significantly greater (42.6 ± 5.5 mm), compared with the preexercise length (39.6 ± 5.7 mm) (P = 0.001). Torque decrement at optimum length was 27.0 ± 1.8% following the exercise protocol, and the joint angle of peak isometric torque production was shifted from 98.8 ± 1.3 to 106.5 ± 1.5°, resulting in a significant 7.7 ± 1.3° shift of the torque-angle relationship to the right (P < 0.001). Isometric torque values were significantly smaller postexercise compared with preexercise at every joint angle (P < 0.05, Fig. 9).



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  		Fig. 9. Torque-joint angle relationship (force-length relationship) before ({circ}) and after ({bullet}) 1 bout (50 repetitions) of lengthening contractions. Note the decreased isometric torque following exercise. Inset: normalized torque-joint angle relationship. Note the shift of peak torque production to longer muscle lengths (greater joint angles) after eccentric exercise. Values are means ± SE; n = 9.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
APPENDIX
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Disassociation between fiber strain and MTU strain.   Strain-induced muscle injury has been assessed following lengthening contractions using in vitro, in situ, and in vivo approaches. Using these different approaches, several variables have been proposed to significantly influence the magnitude of muscle injury following stretch. These include the force produced (23, 28, 48, 49, 61) and work performed during stretch (11, 43, 58), the Lo of the muscle before stretch (7, 28, 59), and fiber strain (7, 38, 39, 59). Although subcellular muscle injury is arguably dependent on the magnitude of fiber strain during active lengthening (10, 38), to date, no systematic analysis of fiber strain has been performed during a controlled active-lengthening protocol. Instead, fiber strains have traditionally been estimated from known MTU strains, assuming that fiber elongations mirror MTU elongations. In vitro and in situ fiber lengths have typically been approximated by multiplying a reference muscle length by the ratio of fiber length to muscle length. Muscle elongations (e.g., 10 mm) were assumed to be equal to fiber elongations (10 mm), and fiber strains were calculated accordingly. In vivo fiber strain estimates have been calculated by dividing MTU strain by the average fiber length (6, 40).

Estimating fiber strains as outlined above may contain errors because of the compliance of the series elastic structures in the MTU complex (70). A compliant actuator has a long tendon compared with fiber length, resulting in a disassociation of fiber length changes from MTU length changes when muscle force varies during dynamic contractions. In an effort to reduce these effects of compliance on the disassociation of fiber and MTU length changes, the external tendon is often removed for in vitro preparations, thereby essentially producing a "stiff actuator." Also, preactivation, ranging up to 400 ms before stretch, has been used as a method to stiffen the MTU complex (10, 11, 14, 28, 31, 52, 64, 68, 69). Care needs to be taken when preactivating a muscle that the force reached at the beginning of the stretch is about the same as the force during the stretch, as this reduces fiber and MTU length disassociations associated with changing muscle force. Fiber and MTU length disassociations are further exacerbated with in vivo preparations, where tendons are intact and muscle length and force change continuously. For in vivo testing, using muscle length as an indicator of fiber length becomes untenable for most situations.

Recently, Peters et al. (52) estimated fiber strain in the EDL to be greater than fiber strain in the TA in the rat, during a noninvasive in vivo active-lengthening protocol. They found that injury in the EDL was less than that in the TA; thus the question arises: was fiber strain accurately estimated, or is fiber strain not related to muscle injury (at least when comparing two muscles)? Because of the extensive studies on fiber strain and injury (3, 9, 11, 38, 69), as well as the results presented here, we feel that calculations of fiber strains based on MTU strains for intact, noninvasive, in vivo studies may be inappropriate.

Measured fiber strains.   Mean net strain (Dr – A1 or Lo) has been calculated in the past, starting with the muscle activated (9, 10, 35, 36, 58) or in the passive state (26, 27). With the muscle activated, net strain is similar to what we have defined as active strain, and what is typically referred to simply as "fiber strain" in the literature (10, 16, 26, 27, 44, 58). With the muscle passive before stretch (as was done in this study), fiber shortening will occur before fiber stretching. Therefore, starting with the muscle passive would typically give smaller net strains than starting with the muscle fully activated. This approach, although by no means physiological, does approximate many physiological conditions and represents fiber dynamics more adequately (29).

As an example, let us consider a study performed by Lieber et al. (40) in which a setup virtually identical to ours was used. They estimated fiber strains of 10% in the NZW rabbit TA for muscle lengthening through 30° of tibiotarsal plantar flexion, assuming a one-to-one relationship between MTU and fiber elongation. This value of 10% is similar to our measured active strains (8–11% across sets and repetitions), but it is very different from the net strains measured directly (–0.3 to –0.2%) and does not accurately depict the changes in strain magnitude within each set. Overall, estimated fiber strains in vitro are probably best compared with what we defined as active fiber strain in our study.

However, as we have shown, active fiber strain does not account for the greatest magnitude or rate of stretch to the fibers during repetitive stretch shortening. Although active strain has been implicated in the contractile damage following eccentric exercise, relaxation strain was responsible for lengthening the fibers not only to their greatest lengths but also at the highest rate during the stretch-shortening cycle. This high rate and magnitude of strain, although occurring while torque is decreasing, may contribute to damaging the fibers, if sarcomere heterogeneity has occurred during the preceding active strain. Sarcomeres, operating on the descending limb of their force-length relationships, may be lengthened rapidly beyond overlap during this phase and so may contribute to the observed muscle injury.

Ultimately, maximum fiber strain may be the best predictor of muscle damage. It is the sum of active strain and relaxation strain. Its relationship with active strain is negative and with relaxation strain is positive, i.e., the greater the relaxation strain, the greater the maximum strain. This result further advances the idea that relaxation strain, which we expect to occur under physiological conditions but not necessarily in typical laboratory testing, may be an important factor in muscle injury and damage. This concept is hypothetical and warrants further investigation.

Temporal effects on fiber strain magnitudes.   Fiber strains not only varied depending on how they were defined, but also varied with time. Overall, there was a group of strain measures that varied within sets and a group that varied between sets. Active fiber shortening significantly diminished within sets and across sets (Fig. 2, APPENDIX). Within each set, torque decreased, which resulted in decreased active fiber shortening, as one would expect. However, across sets, active fiber shortening decreased for the same torque (Fig. 3), suggesting that the SEC became stiffer with an increasing number of sets. This result is illustrated schematically in Fig. 10. If, for a given torque and a given MTU complex length, the SEC is stiffer than a reference value, the SEC length will be shorter and the CE length will be greater. Therefore, we may conclude, based on the temporal results of active fiber shortening, that the SEC became stiffer and the CE became more compliant with increasing numbers of eccentric exercise sets (Fig. 10).



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  		Fig. 10. Schematic force-elongation curves for the series elastic component (SEC) of muscle illustrating the effect of increasing stiffness. For an increased stiffness of the SEC (K2 > K1), a given force production (F1 = F2) at a given MTU length will result in a decreased length of the SEC and an increased length of the CE (inset). post, Postexercise; pre, preexercise.

 
Active strain significantly increased within each set, but it did not change between sets. This appears to be due to the effects of fatigue, which were length dependent. Specifically, the mean torque at the end of active stretch decreased to a greater extent (–3.5 ± 0.3%) than the torque at the beginning of active stretch (–2.1 ± 0.3%). Because the stiffness of the SEC appears to remain about constant within sets, one would expect the decrease in SEC lengths to be more pronounced at the end, rather than the beginning, of active fiber strain. As a result, fiber length increases within each set should be greater at the end of active stretch compared with the beginning, thereby producing the increase in active fiber strain observed within each set.

Relaxation strain decreases within each set and decreases from set 1 to set 5 (Fig. 5). Because fiber lengths remain virtually constant at the end of the relaxation phase (Dr, Fig. 1, APPENDIX), the decrease in relaxation strain is primarily explained by the increase in fiber lengths at Cr within sets. The increase in fiber lengths at Cr within sets, in turn, can be explained by the reduction in torque within a set, which results in a decreased elongation of the SEC and a corresponding increase in length (stretch) of the fibers (CE). As previously shown (Fig. 3), the stiffness of the SEC increases between sets, thereby increasing fiber lengths for a given amount of torque. This causes the fiber lengths to increase at the beginning of the relaxation phase across sets (Cr, APPENDIX), thereby producing the observed decrease in relaxation strains from set 1 to set 5.

Net strains and repetition strains each varied within sets but, overall, experienced minimal temporal effects. Net strain was measured from A1 (constant, Lo) to Dr (Fig. 1). Because Dr remained nearly constant (APPENDIX), net strains did not exhibit great variations within or across sets. Repetition strain was measured from Ar to Dr (Fig. 1), and, because Ar also remained virtually constant within and across sets, except for the very first stretch-shortening cycle, repetition strain did not exhibit temporal effects.

Injury induced through repetitive stretch-shortening cycles.   Following the repetitive stretch-shortening exercise protocol, we observed a significant rightward shift of the torque-joint angle relationship. Such a shift has been proposed to be a reliable indicator of muscle injury (32, 47, 53, 64, 65) and has been said to be insensitive to the effects of fatigue (64). The postexercise torque-joint angle relationship was measured immediately following the exercise protocol. In a previous study, utilizing an identical setup to the one used here, we found a significantly greater reduction in torque following eccentric compared with isometric exercise protocol and associated this greater reduction with injury induced in the eccentric protocol (12). In addition, the observation that fiber lengths were significantly longer at peak torque production following the exercise protocol compared with before indicated that optimal filament overlap of functioning sarcomeres was associated with an increased fiber length following exercise. This result could be explained by areas of elongated or damaged sarcomeres within the fibers, resulting in increased compliance, partially contributing to the rightward shift of the torque-angle relationship (47, 63–65). Such damaged fibers could also explain the increased CE compliance with increasing numbers of eccentric repetitions.

Although it has been commonplace to assume that fiber lengths mimic MTU length changes during in vitro lengthening protocols, the associated fiber strains and temporal effects are complex in vivo. Progressive damage of the CE has been associated with active lengthening of fibers during eccentric exercise for some time, but this disregards the fiber dynamics during MTU shortening during repeated cycles. One potentially injurious aspect of fiber dynamics that we have identified was the relaxation strain, when fibers are stretched at the greatest rate to the longest length during each cycle. Relaxation strain is not a passive strain, as force is still produced despite deactivation of the muscle. This may add to the potential etiology of muscle injury in vivo, as the combination of high rate of stretch and low force production may exacerbate sarcomere nonuniformities that are present from the preceding active strain. Stretched sarcomeres may be expected to be on the descending limb of their individual force-length relationship at the end of active strain and may be pulled beyond myofilament overlap during deactivation.

Physiologically, the muscles are generally activated during shortening (14). Active shortening would diminish, or possibly eliminate, the relaxation strain that we observed in this study. In this regard, the time between eccentric and concentric muscle actions may affect the susceptibility to injury based on our findings, and a quick concentric movement may ameliorate the injury susceptibility based on less CE lengthening. However, if the MTU length was kept constant at the end of active lengthening, for a duration that was adequate for force to return to zero, we would expect a greater magnitude of fiber strain during the relaxation phase, as the stretch of the fibers associated with force decay would not be offset, in part, by MTU shortening, as occurred in the protocol used in this study.

In conclusion, because muscle injuries are often associated with structural damage to the fibers, it is fair to assume that fiber stresses and strains are important variables to consider in studies aimed at elucidating mechanisms of stretch-induced injury. In this study, we were able to reproduce the paradoxical relationship between MTU lengthening and fiber shortening at the onset of active-lengthening contractions in vivo. The present results demonstrate that procedures for estimating fiber strains in vitro and in situ may not be appropriate when applied to in vivo protocols, as fiber and MTU strains may be disassociated to a great extent for intact, dynamic conditions. Fiber strains can be much smaller than MTU strains, and great fiber strains can occur while the MTU is shortening. In addition, the temporal effects on fiber strain magnitudes during in vivo, repeated stretch-shortening cycles may be explained not only by fatigue within each set but also by a stiffening of the SEC and an increase in compliance of the CE. Therefore, measurements of real-time function of skeletal muscles in vivo, during repeated stretch-shortening cycles, mayprovide important clues in pinpointing the sequlae of events leading to fiber damage.


   APPENDIX
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 APPENDIX
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Fiber length values and strain calculations for each repetition (r) of the test protocol are given below. Values are means ± SE. For a definition of points A, B, C, and D, refer to Fig. 1. For a definition of the various strains, refer to Fig. 1 and text.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 APPENDIX
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
The Canadian Institutes of Health Research (CIHR) Training Program in Bone and Joint Health, Natural Sciences and Engineering Research Council of Canada, and the CIHR Canada Research Chair Program supported this study.


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   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 APPENDIX
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
The authors thank Tim Leonard and Hoa Nguyen for technical assistance.


   FOOTNOTES
 

Address for reprint requests and other correspondence: W. Herzog, Faculty of Kinesiology, Univ. of Calgary, Calgary, Alberta, Canada T2N 1N4 (E-mail: walter{at}kin.ucalgary.ca)

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.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 APPENDIX
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

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