Lengthening Contractions Research Articles

Deducing a mechanism of all musculoskeletal injuries.

The mechanism of musculoskeletal (MSK) injuries is not well understood. This research applies principles of elastic motion to the anatomy and movement patterns of MSK structures. From this an insight into the application and timing of forces on MSK structures can be established and the mechanism/s of injury derived. All MSK structures demonstrate varying degrees of elasticity. Movement occurs primarily as a consequence of Muscle Tendon Unit (MTU) shortening. The application of an applied external force results in MSK structure lengthening. The MTU acts as a non-idealised Hookean Spring. The resting length of MSK structures is the minimum distance between attachment points. The anatomical constraints results in MSK structures having adequate compressive strength during shortening. Thus MSK injuries only occur during lengthening of the MSK structure. From this with knowledge of MSK movement cycles, we can derive the mechanism of injury. MSK injuries result from an inability to counter applied forces whilst lengthening. Muscles, tendons and ligaments can only injure during their lengthening contraction phase. Insertional tendons and bone near attachment points injure during the MTU shortening phase. Injuries to other MSK structures can occur independent of the lengthening and shortening phases such as direct contact injuries.

Annexin A1 Deficiency does not Affect Myofiber Repair but Delays Regeneration of Injured Muscles.

Repair and regeneration of the injured skeletal myofiber involves fusion of intracellular vesicles with sarcolemma and fusion of the muscle progenitor cells respectively. In vitro experiments have identified involvement of Annexin A1 (Anx A1) in both these fusion processes. To determine if Anx A1 contributes to these processes during muscle repair in vivo, we have assessed muscle growth and repair in Anx A1-deficient mouse (AnxA1−/−). We found that the lack of Anx A1 does not affect the muscle size and repair of myofibers following focal sarcolemmal injury and lengthening contraction injury. However, the lack of Anx A1 delayed muscle regeneration after notexin-induced injury. This delay in muscle regeneration was not caused by a slowdown in proliferation and differentiation of satellite cells. Instead, lack of Anx A1 lowered the proportion of differentiating myoblasts that managed to fuse with the injured myofibers by days 5 and 7 after notexin injury as compared to the wild type (w.t.) mice. Despite this early slowdown in fusion of Anx A1−/− myoblasts, regeneration caught up at later times post injury. These results establish in vivo role of Anx A1 in cell fusion required for myofiber regeneration and not in intracellular vesicle fusion needed for repair of myofiber sarcolemma.

IL-6 RESPONSES TO GLYCAEMIC INDEX DURING RECOVERY FROM EXERCISE

Purpose: This study examined the effect of meal with different glycaemic index (GI) on plasma IL-6 concentration and glucose metabolism after maximal lengthening contractions of the knee extensors. Using a cross-over design, Material : 10 healthy males completed 5 sets of 10 lengthening (eccentric) contractions at 120% 1 repetition-maximum. Subjects were randomized to consume the GI beverage (high-GI, low-GI (15% weight per volume; 3 g/kg BM) or placebo in three times within 10 min following exercise, and again at 50 and 110 min during recovery time. Blood samples were collected before exercise and after 0.60, 180 min and 24 h of recovery. Results: Concentration of plasma IL-6 in HGI group was less than LGI and Pla groups. IL-6 tended to significantly increase after exercise in recovery time in 3 groups (all P < 0.05), except for 24 hours (P = 1.00), furthermore there was significant difference for IL-6 between placebo and high glycemic groups in 3hours after exercise (P=.016). Concentration of serum CK in HGI group was less than LGI and Pla groups, CK was significantly elevated at all times points during recovery in 3 groups (all P < 0.05), except for 1 hour after exercise in HGI group (P = 0.31), but there was no significant difference for CK between groups. Conclusion: In summary, consuming HGI carbohydrate during recovery from exercise attenuate plasma IL-6 concentration.

Increased spinal reflex excitability is associated with enhanced central activation during voluntary lengthening contractions in human spinal cord injury.

This study of chronic incomplete spinal cord injury (SCI) subjects investigated patterns of central motor drive (i.e., central activation) of the plantar flexors using interpolated twitches, and modulation of soleus H-reflexes during lengthening, isometric, and shortening muscle actions. In a recent study of the knee extensors, SCI subjects demonstrated greater central activation ratio (CAR) values during lengthening (i.e., eccentric) maximal voluntary contractions (MVCs), compared with during isometric or shortening (i.e., concentric) MVCs. In contrast, healthy controls demonstrated lower lengthening CAR values compared with their isometric and shortening CARs. For the present investigation, we hypothesized SCI subjects would again produce their highest CAR values during lengthening MVCs, and that these increases in central activation were partially attributable to greater efficacy of Ia-α motoneuron transmission during muscle lengthening following SCI. Results show SCI subjects produced higher CAR values during lengthening vs. isometric or shortening MVCs (all P < 0.001). H-reflex testing revealed normalized H-reflexes (maximal SOL H-reflex-to-maximal M-wave ratios) were greater for SCI than controls during passive (P = 0.023) and active (i.e., 75% MVC; P = 0.017) lengthening, suggesting facilitation of Ia transmission post-SCI. Additionally, measures of spinal reflex excitability (passive lengthening maximal SOL H-reflex-to-maximal M-wave ratio) in SCI were positively correlated with soleus electromyographic activity and CAR values during lengthening MVCs (both P < 0.05). The present study presents evidence that patterns of dynamic muscle activation are altered following SCI, and that greater central activation during lengthening contractions is partly due to enhanced efficacy of Ia-α motoneuron transmission.

Does Blood Flow Restriction Enhance Exercise-mediated Changes In The Plantar Flexors?

The plantar flexor muscle group readily atrophies when exposed to an unloaded environment (i.e. microgravity). There is evidence that the plantar flexors are also resistant to exercise stimuli when compared to other musculature. A rather novel training method called Kaatsu, or blood flow restriction (BFR) training, may potentially provide a substantial resistance training stimulus to the plantar flexors. PURPOSE: To determine if there are differences in strength and body composition after five weeks of training utilizing fatiguing protocols with or without BFR. METHODS: Seven physically inactive subjects (6 male, 1 female) engaged in five weeks of resistance training for the plantar flexors. Each leg was randomly assigned to one of three protocols: 1) high intensity (HIT), 2) low intensity (LIT), or 3) low intensity with blood flow restriction (BFR). Exercise sessions consisted of three sets to fatigue with 1.5 minutes of rest between sets. Each repetition consisted of a maximal shortening contraction followed by a controlled lengthening contraction regulated audibly by a metronome. Exercise was conducted unilaterally on hack squat equipment. Sets were terminated when 80% of full ROM was not obtained for two consecutive repetitions. For BFR, pressure was applied just superior to the proximal patella at 1.3 x systolic blood pressure and was maintained through the duration of the protocol. RESULTS: No significant differences were found with isometric torque although % changes pre-post in peak power across isokinetic velocities ranging from 30 to 240 degrees were significantly greater with LIT. One repetition max (1RM) increased post-training in all groups with a trend towards increased strength at the mid-assessment for BFR only (p=0.0537). Total reps completed were significantly lower and total training volume higher with HIT. Session RPE was not different among protocols. There were no changes in lower leg lean or fat mass as assessed by DXA. CONCLUSIONS: In general, all three training protocols resulted in increased 1RM strength following five weeks of training with no changes in body composition. Supported by NIH grant UL1 TR00153 and the Undergraduate Research Opportunities Program at UCI.

Manual therapy ameliorates delayed onset muscle soreness following the lengthening contraction and modulates muscle metabolites：an animal-model study

Manual therapy ameliorates delayed onset muscle soreness following the lengthening contraction and modulates muscle metabolites：an animal-model study

Extracellular matrix remodeling and its contribution to protective adaptation following lengthening contractions in human muscle.

This study determined the contribution of extracellular matrix (ECM) remodeling to the protective adaptation of human skeletal muscle known as the repeated-bout effect (RBE). Muscle biopsies were obtained 3 hours, 2 days, and 27 days following an initial bout (B1) of lengthening contractions (LCs) and 2 days following a repeated bout (B2) in 2 separate studies. Biopsies from the nonexercised legs served as controls. In the first study, global transcriptomic analysis indicated widespread changes in ECM structural, deadhesive, and signaling transcripts, 3 hours following LC. To determine if ECM remodeling is involved in the RBE, we conducted a second study by use of a repeated-bout paradigm. TNC immunoreactivity increased 10.8-fold following B1, was attenuated following B2, and positively correlated with LC-induced strength loss (r(2) = 0.45; P = 0.009). Expression of collagen I, III, and IV (COL1A1, COL3A1, COL4A1) transcripts was unchanged early but increased 5.7 ± 2.5-, 3.2 ± 0.9-, and 2.1 ± 0.4-fold (P < 0.05), respectively, 27 days post-B1 and were unaffected by B2. Likewise, TGF-β signaling demonstrated a delayed response following LC. Satellite cell content increased 80% (P < 0.05) 2 days post-B1 (P < 0.05), remained elevated 27 days post-B1, and was unaffected by B2. Collectively, the data suggest sequential ECM remodeling characterized by early deadhesion and delayed reconstructive activity that appear to contribute to the RBE.

Manual therapy ameliorates delayed-onset muscle soreness and alters muscle metabolites in rats.

Delayed-onset muscle soreness (DOMS) can be induced by lengthening contraction (LC); it can be characterized by tenderness and movement-related pain in the exercised muscle. Manual therapy (MT), including compression of exercised muscles, is widely used as physical rehabilitation to reduce pain and promote functional recovery. Although MT is beneficial for reducing musculoskeletal pain (i.e. DOMS), the physiological mechanisms of MT remain unclear. In the present study, we first developed an animal model of MT in DOMS; LC was applied to the rat gastrocnemius muscle under anesthesia, which induced mechanical hyperalgesia 2–4 days after LC. MT (manual compression) ameliorated mechanical hyperalgesia. Then, we used capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) to investigate early effects of MT on the metabolite profiles of the muscle experiencing DOMS. The rats were divided into the following three groups; (1) normal controls, (2) rats with LC application (LC group), and (3) rats undergoing MT after LC (LC + MT group). According to the CE-TOFMS analysis, a total of 171 metabolites were detected among the three groups, and 19 of these metabolites were significant among the groups. Furthermore, the concentrations of eight metabolites, including branched-chain amino acids, carnitine, and malic acid, were significantly different between the LC + MT and LC groups. The results suggest that MT significantly altered metabolite profiles in DOMS. According to our findings and previous data regarding metabolites in mitochondrial metabolism, the ameliorative effects of MT might be mediated partly through alterations in metabolites associated with mitochondrial respiration.

Modulation of soleus H-reflex during shortening and lengthening muscle actions in young and older adults.

The H-reflex is dependently modulated during isometric and anisometric muscle actions. However, the manner of the H-reflex modulation during dynamic muscle movements in relation to ageing is less stated in the literature. This study was designed to investigate the effects of ageing on soleus (SOL) H-reflex modulation during dynamic muscle actions. Twenty young (24 ± 4 years of age) and 20 older adults (73 ± 5 years of age) voluntarily participated in the study. The SOL H-reflex was measured during passive and active shortening and lengthening muscle actions in a sitting position. The older group showed a lower ratio of the maximal amplitude of H-reflex to M-wave (SOL Hmax/Mmax) during the passive lengthening than that during the passive shortening (shortening: 0.40 ± 0.22 vs. lengthening: 0.15 ± 0.10, P < 0.05), whereas the SOL Hmax/Mmax ratio of the young group was significantly higher during the shortening than that during the lengthening contractions at maximal effort (shortening: 0.51 ± 0.26 vs. lengthening: 0.37 ± 0.18, P < 0.05). These results suggested different modulations of group Ia afferent inputs to the SOL motoneurons during passive and active dynamic muscle actions between young and older adults.

Muscle force, work and cost: a novel technique to revisit the Fenn effect.

Muscle produces force by forming cross-bridges, using energy released from ATP. While the magnitude and duration of force production primarily determine the energy requirement, nearly a century ago Fenn observed that muscle shortening or lengthening influenced energetic cost of contraction. When work is done by the muscle, the energy cost is increased and when work is done on the muscle the energy cost is reduced. However, the magnitude of the 'Fenn effect' and its mirror ('negative Fenn effect') have not been quantitatively resolved. We describe a new technique coupling magnetic resonance spectroscopy with an in vivo force clamp that can directly quantify the Fenn effect [E=I+W, energy liberated (E) equals the energy cost of isometric force production (I) plus the work done (W)] and the negative Fenn effect (E=I-W) for one muscle, the first dorsal interosseous (FDI). ATP cost was measured during a series of contractions, each of which occurred at a constant force and for a constant duration, thus constant force-time integral (FTI). In all subjects, as the FTI increased with load, there was a proportional linear increase in energy cost. In addition, the cost of producing force greatly increased when the muscle shortened, and was slightly reduced during lengthening contraction. These results, though limited to a single muscle, contraction velocity and muscle length change, do quantitatively support the Fenn effect. We speculate that they also suggest that an elastic element within the FDI muscle functions to preserve the force generated within the cross-bridges.

Stretch speed-dependent myofiber damage and functional deficits in rat skeletal muscle induced by lengthening contraction.

Exercise involving lengthening contraction (LC) often results in delayed myofiber damage and functional deficits over the ensuing days. The present study examined whether the stretch speed of LC is a determinant of damage severity. Under isoflurane anesthesia, LC was repeatedly induced in rat ankle extensor muscles at different stretch speeds (angular velocities of 50, 100, 200, and 400 deg/sec) over a fixed stretch range of motion (90°). The number of muscle fibers labeled with Evans blue dye, a marker of muscle fiber damage associated with increased membrane permeability, increased with the angular velocity of LC (by 20% of all myofibers at 400 deg/sec). Muscle fibers with cross‐sectional areas in the range of 3600–4800 μm2, corresponding to type IIb fiber size, exhibited the most severe damage as revealed by the largest decrease in the number of fibers 3 days after LC at 200 deg/sec, suggesting that muscle damage occurred preferentially in type IIb myofibers. Isometric torque of dorsiflexion measured 2 days after LC decreased progressively with LC angular velocity (by 68% reduction at 400 deg/sec). The angular velocity of muscle stretch during LC is thus a critical determinant of the degree of damage, and LC appears to damage type IIb fibers preferentially, resulting in a disproportionate reduction in isometric torque. This LC response is an important consideration for the design of physical conditioning and rehabilitation regimens.

G.P.84: Muscle physiology properties of mouse models for Duchenne muscular dystrophy

Duchenne muscular dystrophy is a severe muscle wasting disorder, caused by the loss of dystrophin. Since dystrophin is needed to maintain fiber stability during contractions, its absence results in fragile fibers, which are prone to exercise induced damage. In contrast to DMD patients, the mdx mouse model is less severely affected due, at least in part, to overexpression of the dystrophin homologue utrophin. To determine the role of utrophin in maintaining muscle strength and integrity, we performed in vivo force measurements in the tibialis anterior (TA) of 8week old dystrophic mice expressing utrophin on two ( mdx ), one ( mdx-utrn+/ −) or zero alleles ( mdx-utrn − / −). The specific force was significantly lower in all dystrophic compared to wild type mice, and mdx-utrn − / − mice performed significantly worse than mdx and mdx-utrn+/ − mice. Although mdx mice produced lower forces than wild type mice, the force frequency relationship curves followed a similar pattern. A substantial increase in force was observed upon stimulation with higher frequencies (>80Hz) in mdx mice. Contrastingly, lower frequencies ( mdx-utrn+/ − mice, while their maximum specific force was comparable to mdx mice. This suggested that the proportions of slow and fast fibers differed between the dystrophic models. Histologically, we confirmed a shift towards slow fibers in the TAs of mdx-utrn+/ − and −/− mice, whereas in mdx and wild type mice predominantly fast fibers were found. Eccentric (lengthening) contractions provoked a large force drop in mdx mice, while wild type mice were resistant. Interestingly, slow muscle fibers of mdx-utrn+/ − mice enabled better maintenance of force during eccentric contractions than seen in mdx mice. Mdx-utrn − / − mice did not show a drop in force as they were already very weak at protocol initiation. These results suggest that loss of utrophin provokes a shift towards slow fibers which partly preserves muscle function in heterozygotes.

A model for creating a single stretch injury in murine biarticular muscle

BackgroundWe developed a single stretch injury model to create damage near the musculotendinous junction (MTJ) of the gastrocnemius muscle in mice. Our hypothesis was that magnitude of muscle injury could be controlled by stepped shortening of the Achilles tendon (AT) prior to a lengthening contraction. Increased shortening would result in a greater isometric torque deficit and morphological damage 24 hours post-injury.MethodsSixteen mice were randomly assigned to sham or injury predicated on stepped increases in AT shortening. The AT was exposed and placed in a customized stainless steel roller-clamp system to achieve a specific level of shortening; 0 mm (resting length), 0.7 mm or 1.4 mm. Plantar flexors were stimulated to tetany with a needle electrode and then actively lengthened at 450°/sec from neutral to 75° of dorsiflexion. Passive and isometric torques were measured pre- and immediately post-injury. Isometric torque was measured again 24 h post-injury. Peak isokinetic torque was recorded during eccentric injury.ResultsInjury resulted in decreased passive and immediate absolute isometric torque only when induced with AT shortening. The percentage of pre-injury isometric torque was significantly lower in the AT shortened groups immediately and 24 h post-injury, but was unaffected by the level of shortening. Relative isometric torque deficits were noted in the 0 mm group only 24 h post-injury. Peak isokinetic torque during injury was similar in all groups. Histological evaluation 24 h post-injury revealed increased morphological damage near the MTJ in the AT shortened groups.ConclusionSingle stretch with AT shortening created morphological damage near the MTJ and isometric torque deficits immediately and 24 h post-injury, but the magnitude of damage could not be titrated with stepped increases in AT shortening. This model provides an opportunity to utilize transgenic mice in order to elucidate inflammatory mediators that promote regeneration and inhibit fibrosis in order to optimize therapeutic interventions for complete functional recovery.

Motor unit activity after eccentric exercise and muscle damage in humans

It is well known that unaccustomed eccentric exercise leads to muscle damage and soreness, which can produce long-lasting effects on muscle function. How this muscle damage influences muscle activation is poorly understood. The purpose of this brief review is to highlight the effect of eccentric exercise on the activation of muscle by the nervous system, by examining the change in motor unit activity obtained from surface electromyography (EMG) and intramuscular recordings. Previous research shows that eccentric exercise produces unusual changes in the EMG–force relation that influences motor performance during isometric, shortening and lengthening muscle contractions and during fatiguing tasks. When examining the effect of eccentric exercise at the single motor unit level, there are substantial changes in recruitment thresholds, discharge rates, motor unit conduction velocities and synchronization, which can last for up to 1 week after eccentric exercise. Examining the time course of these changes suggests that the increased submaximal EMG after eccentric exercise most likely occurs through a decrease in motor unit conduction velocity and an increase in motor unit activity related to antagonist muscle coactivation and low-frequency fatigue. Furthermore, there is a commonly held view that eccentric exercise produces preferential damage to high-threshold motor units, but the evidence for this in humans is limited. Further research is needed to establish whether there is preferential damage to high-threshold motor units after eccentric exercise in humans, preferably by linking changes in motor unit activity with estimates of motor unit size using selective intramuscular recording techniques.

Geared up to stretch: pennate muscle behavior during active lengthening

Many locomotor activities require muscles to actively lengthen, dissipate energy and decelerate the body. These eccentric contractions can disrupt cytoskeletal structures within myofibrils and reduce force output. We examined how architectural features of pennate muscles can provide a protective mechanism against eccentric muscle damage by limiting fascicle lengthening. It has been previously shown that the angled fibers of pennate muscles change orientation when shortening. This change in fiber orientation can amplify fascicle shortening, resulting in a velocity advantage at the level of the muscle-tendon unit (MTU) that is characterized by a gear ratio (MTU velocity/fascicle velocity). A muscle's architectural gear ratio (AGR) has been shown to vary as a function of force during shortening, while AGR during lengthening remains largely unknown. We independently measured fascicle length and MTU length in vitro in the bullfrog plantaris. We characterized the muscle's force-velocity curve and AGR during both shortening and lengthening across a broad range of forces (10-190% peak isometric force). AGR was measured during the isotonic portion of each contraction, to eliminate possible contributions of series elasticity to MTU length changes. We found that gear ratio varies with force during both shortening and lengthening contractions. The highest AGR was observed during lengthening contractions, indicating that lengthening of the MTU can occur with relatively little stretch of the fascicle. As fascicle strain is considered an important determinant of muscle damage, a high gear ratio may afford pennate muscles protection against the damaging effects of active lengthening.

Physical principles demonstrate that the biceps femoris muscle relative to the other hamstring muscles exerts the most force: implications for hamstring muscle strain injuries

Of the hamstring muscle group the biceps femoris muscle is the most commonly injured muscle in sports requiring interval sprinting. The reason for this observation is unknown. The objective of this study was to calculate the forces of all three hamstring muscles, relative to each other, during a lengthening contraction to assess for any differences that may help explain the biceps femoris predilection for injury during interval sprinting. To calculate the displacement of each individual hamstring muscle previously performed studies on cadaveric anatomical data and hamstring kinematics during sprinting were used. From these displacement calculations for each individual hamstring muscle physical principles were then used to deduce the proportion of force exerted by each individual hamstring muscle during a lengthening muscle contraction. These deductions demonstrate that the biceps femoris muscle is required to exert proportionally more force in a lengthening muscle contraction relative to the semimembranosus and semitendinosus muscles primarily as a consequence of having to lengthen over a greater distance within the same time frame. It is hypothesized that this property maybe a factor in the known observation of the increased susceptibility of the biceps femoris muscle to injury during repeated sprints where recurrent higher force is required.

Conceptual Framework for Strengthening Exercises to Prevent Hamstring Strains

High-speed running accounts for the majority of hamstring strains in many sports. The terminal swing phase is believed to be the most hazardous as the hamstrings are undergoing an active lengthening contraction in a long muscle length position. Prevention-based strength training mainly focuses on eccentric exercises. However, it appears crucial to integrate other parameters than the contraction type. Therefore, the aim of this study is to present a conceptual framework based on six key parameters (contraction type, load, range of motion, angular velocity, uni-/bilateral exercises, kinetic chain) for the hamstring's strength exercise for strain prevention. Based on the biomechanical parameters of sprinting, it is proposed to use high-load eccentric contractions. The movement should be performed at a slow to moderate angular velocity and focused at the knee joint, while the hip is kept in a large flexion position in order to reach a greater elongation stress of the hamstrings than in the terminal swing phase. In this way, we believe that, during sprinting, athletes would be better trained to brake the knee extension effectively in the whole range of motion without overstretch of the hamstrings. Finally, based on its functional application, unilateral open kinetic chain should be preferred.

Muscular Heat and Mechanical Pain Sensitivity After Lengthening Contractions in Humans and Animals

Mechanical sensitivity of muscle nociceptors was previously shown to increase 2 days after lengthening contractions (LC), but heat sensitivity was not different despite nerve growth factor (NGF) being upregulated in the muscle during delayed-onset muscle soreness (DOMS). The discrepancy of these results and lack of other reports drove us to assess heat sensitivity during DOMS in humans and to evaluate the effect of NGF on the heat response of muscle C-fibers. Pressure pain thresholds and pain intensity scores to intramuscular injection of isotonic saline at 48°C and capsaicin were recorded in humans after inducing DOMS. The response of single unmyelinated afferents to mechanical and heat stimulations applied to their receptive field was recorded from muscle-nerve preparations in vitro. In humans, pressure pain thresholds were reduced but heat and capsaicin pain responses were not increased during DOMS. In rats, the mechanical but not the heat sensitivity of muscle C-fibers was increased in the LC group. NGF applied to the receptive field facilitated the heat sensitivity relative to the control. The absence of facilitated heat sensitivity after LC, despite the NGF sensitization, may be explained if the NGF concentration produced after LC is not sufficient to sensitize nociceptor response to heat. PerspectiveThis article presents new findings on the basic mechanisms underlying hyperalgesia during DOMS, which is a useful model to study myofascial pain syndrome, and the role of NGF on muscular nociception. This might be useful in the search for new pharmacologic targets and therapeutic approaches.

English

Since the pioneering work of Hough in 1902 (1) the term ‘delayed onset muscle soreness (DOMS)’ has dominated the field of athletic recovery. DOMS typically occurs after exercise induced muscle damage (EIMD), particularly if the exercise is unaccustomed or involves a large amount of eccentric (muscle lengthening) contractions. The symptoms of EIMD manifest as a temporary reduction in muscle force, disturbed proprioceptive acuity, increases in inflammatory markers both within the injured muscle and in the blood as well as increased muscle soreness, stiffness and swelling. The intensity of discomfort and soreness associated with DOMS increases within the first 24 hours, peaks between 24 and 72 hours, before subsiding and eventually disappearing 5-7 days after the exercise. Consequently, DOMS may interfere with athletic training or competition and several recovery interventions have been utilised by athletes and coaches in an attempt to offset the negative effects...

P.20.6 Muscle physiology properties of mouse models for Duchenne muscular dystrophy

Duchenne muscular dystrophy is a severe muscle wasting disorder, caused by the loss of dystrophin. Since dystrophin is needed to maintain fiber stability during contractions, its absence results in fragile fibers, which are prone to exercise induced damage. In contrast to DMD patients, the mdx mouse model is less severely affected due, at least in part, to overexpression of the dystrophin homologue utrophin. To determine the role of utrophin in maintaining muscle strength and integrity, we performed in vivo force measurements in the tibialis anterior (TA) of 8week old dystrophic mice expressing utrophin on two (mdx), one (mdx-utrn+/−) or zero alleles (mdx-utrn−/−). The specific force was significantly lower in all dystrophic compared to wild type mice, and mdx-utrn−/− mice performed significantly worse than mdx and mdx-utrn+/− mice. Although mdx mice produced lower forces than wild type mice, the force frequency relationship curves followed a similar pattern. A substantial increase in force was observed upon stimulation with higher frequencies (>80Hz) in mdx mice. Contrastingly, lower frequencies (<80Hz) resulted in higher forces in mdx-utrn+/− mice, while their maximum specific force was comparable to mdx mice. This suggested that the proportions of slow and fast fibers differed between the dystrophic models. Histologically, we confirmed a shift towards slow fibers in the TAs of mdx-utrn+/− and −/− mice, whereas in mdx and wild type mice predominantly fast fibers were found. Eccentric (lengthening) contractions provoked a large force drop in mdx mice, while wild type mice were resistant. Interestingly, slow muscle fibers of mdx-utrn+/− mice enabled better maintenance of force during eccentric contractions than seen in mdx mice. Mdx-utrn−/− mice did not show a drop in force as they were already very weak at protocol initiation. These results suggest that loss of utrophin provokes a shift towards slow fibers which partly preserves muscle function in heterozygotes.