Early metabolic changes measured by 1H MRS in healthy and dystrophic muscle after injury

Skeletal muscle injury is often assessed by clinical findings (history, pain, tenderness, strength loss), by imaging, or by invasive techniques. The purpose of this work was to determine if in vivo proton magnetic resonance spectroscopy ((1)H MRS) could reveal metabolic changes in murine skeletal muscle after contraction-induced injury. We compared findings in the tibialis anterior muscle from both healthy wild-type (WT) muscles (C57BL/10 mice) and dystrophic (mdx mice) muscles (an animal model for human Duchenne muscular dystrophy) before and after contraction-induced injury. A mild in vivo eccentric injury protocol was used due to the high susceptibility of mdx muscles to injury. As expected, mdx mice sustained a greater loss of force (81%) after injury compared with WT (42%). In the uninjured muscles, choline (Cho) levels were 47% lower in the mdx muscles compared with WT muscles. In mdx mice, taurine levels decreased 17%, and Cho levels increased 25% in injured muscles compared with uninjured mdx muscles. Intramyocellular lipids and total muscle lipid levels increased significantly after injury but only in WT. The increase in lipid was confirmed using a permeable lipophilic fluorescence dye. In summary, loss of torque after injury was associated with alterations in muscle metabolite levels that may contribute to the overall injury response in mdx mice. These results show that it is possible to obtain meaningful in vivo (1)H MRS regarding skeletal muscle injury.     

Muscle activity pattern dependent pain development and alleviation

Muscle activity is for decades considered to provide health benefits irrespectively of the muscle activity pattern performed and whether it is during e.g. sports, transportation, or occupational work tasks. Accordingly, the international recommendations for public health-promoting physical activity do not distinguish between occupational and leisure time physical activity. However, in this body of literature, attention has not been paid to the extensive documentation on occupational physical activity imposing a risk of impairment of health – in particular musculoskeletal health in terms of muscle pain. Focusing on muscle activity patterns and musculoskeletal health it is pertinent to elucidate the more specific aspects regarding exposure profiles and body regional pain. Static sustained muscle contraction for prolonged periods often occurs in the neck/shoulder area during occupational tasks and may underlie muscle pain development in spite of rather low relative muscle load. Causal mechanisms include a stereotype recruitment of low threshold motor units (activating type 1 muscle fibers) characterized by a lack of temporal as well as spatial variation in recruitment. In contrast during physical activities at leisure and sport the motor recruitment patterns are more dynamic including regularly relatively high muscle forces – also activating type 2 muscles fibers – as well as periods of full relaxation even of the type 1 muscle fibers. Such activity is unrelated to muscle pain development if adequate recovery is granted. However, delayed muscle soreness may develop following intensive eccentric muscle activity (e.g. down-hill skiing) with peak pain levels in thigh muscles 1–2 days after the exercise bout and a total recovery within 1 week. This acute pain profile is in contrast to the chronic muscle pain profile related to repetitive monotonous work tasks. The painful muscles show adverse functional, morphological, hormonal, as well as metabolic characteristics. Of note is that intensive muscle strength training actually may rehabilitate painful muscles, which has recently been repeatedly proven in randomized controlled trials. With training the maximal muscle activation and strength can be shown to recover, and consequently allow for decreased relative muscle load during occupational repetitive work tasks. Exercise training induces adaptation of metabolic and stress-related mRNA and protein responses in the painful muscles, which is in contrast to the responses evoked during repetitive work tasks per se.     

Measurement and evaluation of postural load in occupational work situations

This paper describes methodological considerations and problems experienced when quantifying muscle load in occupational work situations. A system for the quantification of the health effect of prolonged muscle load on the shoulder muscles is also described. Combined measurements of postural load and health effects can be used in a quantitative evaluation of postural load as a risk factor for the development of musculo-skeletal injury. Postural muscle load may be quantified by electromyography or by biomechanical methods. Problems associated with quantitative electromyography are described, including selective inhibition of functional compartments in a muscle. This phenomenon results in other compartments coming under proportionally higher strain, disturbing the force-EMG calibration curves. It is suggested that fatigue measurements, indicated by a shift in the centre frequency of the EMG frequency spectrum, are not easily used for evaluation of vocational EMG recordings if the purpose is to indicate the risk of occupational muscle injury. Load measurements using biomechanical methods may provide an acceptable alternative to electromyography, but more work is required before these methods can be used on a routine basis.     

The influence of altering push force effectiveness on upper extremity demand during wheelchair propulsion

Manual wheelchair propulsion has been linked to a high incidence of overuse injury and pain in the upper extremity, which may be caused by the high load requirements and low mechanical efficiency of the task. Previous studies have suggested that poor mechanical efficiency may be due to a low effective handrim force (i.e. applied force that is not directed tangential to the handrim). As a result, studies attempting to reduce upper extremity demand have used various measures of force effectiveness (e.g., fraction effective force, FEF) as a guide for modifying propulsion technique, developing rehabilitation programs and configuring wheelchairs. However, the relationship between FEF and upper extremity demand is not well understood. The purpose of this study was to use forward dynamics simulations of wheelchair propulsion to determine the influence of FEF on upper extremity demand by quantifying individual muscle stress, work and handrim force contributions at different values of FEF. Simulations maximizing and minimizing FEF resulted in higher average muscle stresses (23% and 112%) and total muscle work (28% and 71%) compared to a nominal FEF simulation. The maximal FEF simulation also shifted muscle use from muscles crossing the elbow to those at the shoulder (e.g., rotator cuff muscles), placing greater demand on shoulder muscles during propulsion. The optimal FEF value appears to represent a balance between increasing push force effectiveness to increase mechanical efficiency and minimize upper extremity demand. Thus, care should be taken in using force effectiveness as a metric to reduce upper extremity demand.     

Exercise-induced respiratory muscle fatigue: implications for performance.

It is commonly held that the respiratory system has ample capacity relative to the demand for maximal O(2) and CO(2) transport in healthy humans exercising near sea level. However, this situation may not apply during heavy-intensity, sustained exercise where exercise may encroach on the capacity of the respiratory system. Nerve stimulation techniques have provided objective evidence that the diaphragm and abdominal muscles are susceptible to fatigue with heavy, sustained exercise. The fatigue appears to be due to elevated levels of respiratory muscle work combined with an increased competition for blood flow with limb locomotor muscles. When respiratory muscles are prefatigued using voluntary respiratory maneuvers, time to exhaustion during subsequent exercise is decreased. Partially unloading the respiratory muscles during heavy exercise using low-density gas mixtures or mechanical ventilation can prevent exercise-induced diaphragm fatigue and increase exercise time to exhaustion. Collectively, these findings suggest that respiratory muscle fatigue may be involved in limiting exercise tolerance or that other factors, including alterations in the sensation of dyspnea or mechanical load, may be important. The major consequence of respiratory muscle fatigue is an increased sympathetic vasoconstrictor outflow to working skeletal muscle through a respiratory muscle metaboreflex, thereby reducing limb blood flow and increasing the severity of exercise-induced locomotor muscle fatigue. An increase in limb locomotor muscle fatigue may play a pivotal role in determining exercise tolerance through a direct effect on muscle force output and a feedback effect on effort perception, causing reduced motor output to the working limb muscles.     

Work-Related Pain in Extrinsic Finger Extensor Musculature of Instrumentalists Is Associated with Intracellular pH Compartmentation during Exercise

Background

Although non-specific pain in the upper limb muscles of workers engaged in mild repetitive tasks is a common occupational health problem, much is unknown about the associated structural and biochemical changes. In this study, we compared the muscle energy metabolism of the extrinsic finger extensor musculature in instrumentalists suffering from work-related pain with that of healthy control instrumentalists using non-invasive phosphorus magnetic resonance spectroscopy (³¹P-MRS). We hypothesize that the affected muscles will show alterations related with an impaired energy metabolism.

Methodology/Principal Findings

We studied 19 volunteer instrumentalists (11 subjects with work-related pain affecting the extrinsic finger extensor musculature and 8 healthy controls). We used ³¹P-MRS to find deviations from the expected metabolic response to exercise in phosphocreatine (PCr), inorganic phosphate (Pi), Pi/PCr ratio and intracellular pH kinetics. We observed a reduced finger extensor exercise tolerance in instrumentalists with myalgia, an intracellular pH compartmentation in the form of neutral and acid compartments, as detected by Pi peak splitting in ³¹P-MRS spectra, predominantly in myalgic muscles, and a strong association of this pattern with the condition.

Conclusions/Significance

Work-related pain in the finger extrinsic extensor muscles is associated with intracellular pH compartmentation during exercise, non-invasively detectable by ³¹P-MRS and consistent with the simultaneous energy production by oxidative metabolism and glycolysis. We speculate that a deficit in energy production by oxidative pathways may exist in the affected muscles. Two possible explanations for this would be the partial and/or local reduction of blood supply and the reduction of the muscle oxidative capacity itself.     

Ultrastructural abnormalities of muscle spindles in the rat masseter muscle with malocclusion-induced damage

Human temporomandibular disorders due to disturbed occlusal mechanics are characterized by sensory, motor and autonomic symptoms, possibly related to muscle overwork and fatigue. Our previous study in rats with experimentally-induced malocclusion due to unilateral molar cusp amputation showed that the ipsilateral masseter muscles undergo morphological and biochemical changes consistent with muscle hypercontraction and ischemia. In the present study, the masseter muscle spindles of the same malocclusion-bearing rats were examined by electron microscopy. Sham-operated rats were used as controls. In the treated rats, clear-cut alterations of the muscle spindles were observed 26 days after surgery, when the extrafusal muscle showed the more severe damage. The fusal alterations affected predominantly capsular cells, intrafusal muscle fibers and sensory nerve endings. These results suggest that in the malocclusion-bearing rats, an abnormal reflex regulation of the motor activity of the masticatory muscles may take place. They also allow us to hypothesize that muscle spindle alterations might be involved in the pathogenesis of human temporomandibular disorders.     

Extracts from MDX and normal mouse skeletal muscle contain similar levels of mitogenic activity for myoblasts

The mdx mouse has been used as an animal model for human Duchenne muscular dystrophy (DMD). Unlike DMD, skeletal muscles of mdx mice undergo successful regeneration and do not show extensive fibrosis and functional impairment. Growth factors have been proposed to be involved in muscle growth and regeneration. We compared mitogenic activity for skeletal myoblasts released after injury in mdx and control mice, using crushed muscle extract (CME) as a model system. We found that CMEs from normal and mdx mice contained similar mitogenic activities per microgram protein, and produced similar maximal levels of mitogenic stimulation. Skeletal muscles from mdx mice, however, released higher amounts of CME protein per gram of muscle weight compared to controls, possibly as a result of histological or physiological alterations in mdx muscle tissue. Adequate mitogenic activity in CME from mdx muscles may be related to successful muscle regeneration in mdx mice.     

Loss of the Inducible Hsp70 Delays the Inflammatory Response to Skeletal Muscle Injury and Severely Impairs Muscle Regeneration

Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecular mechanisms which coordinate these events are only beginning to be defined. In the current study we demonstrate that Heat shock protein 70 (Hsp70) is increased following muscle injury, and is necessary for the normal sequence of events following severe injury induced by cardiotoxin, and physiological injury induced by modified muscle use. Indeed, Hsp70 ablated mice showed a significantly delayed inflammatory response to muscle injury induced by cardiotoxin, with nearly undetected levels of both neutrophil and macrophage markers 24 hours post-injury. At later time points, Hsp70 ablated mice showed sustained muscle inflammation and necrosis, calcium deposition and impaired fiber regeneration that persisted several weeks post-injury. Through rescue experiments reintroducing Hsp70 intracellular expression plasmids into muscles of Hsp70 ablated mice either prior to injury or post-injury, we confirm that Hsp70 optimally promotes muscle regeneration when expressed during both the inflammatory phase that predominates in the first four days following severe injury and the regenerative phase that predominates thereafter. Additional rescue experiments reintroducing Hsp70 protein into the extracellular microenvironment of injured muscles at the onset of injury provides further evidence that Hsp70 released from damaged muscle may drive the early inflammatory response to injury. Importantly, following induction of physiological injury through muscle reloading following a period of muscle disuse, reduced inflammation in 3-day reloaded muscles of Hsp70 ablated mice was associated with preservation of myofibers, and increased muscle force production at later time points compared to WT. Collectively our findings indicate that depending on the nature and severity of muscle injury, therapeutics which differentially target both intracellular and extracellular localized Hsp70 may optimally preserve muscle tissue and promote muscle functional recovery.     

Shoulder muscle co-ordination during chronic and acute experimental neck-shoulder pain. An occupational pain study

Little is known about the mechanisms leading to chronic neck-shoulder musculoskeletal disorders (MSD). The aim of the present study was to investigate and compare motor function during controlled, low load, repetitive work together with chronic or acute experimental neck-shoulder pain. The clinical study was performed on workers with (n = 12) and without (n = 6) chronic neck-shoulder pain. In the experimental study, experimental muscle pain was induced in healthy subjects by intra-muscular injection of hypertonic saline into the trapezius muscle (n = 10). The assessed parameters related to motor performance were: work task event duration, cutting forces, surface electromyogram (EMG) activity in four shoulder muscles, displacement of the centre of pressure, and arm and trunk 3D movements. For controlled cutting force levels, chronic and acute experimental pain provoked a series of changes: a decreased working rhythm and a protective reorganisation of muscle synergy (experimental study), higher EMG frequency contents which may indicate altered motor unit recruitment, and greater postural activity and a tendency towards increased arm and trunk movements. These pain-related changes can play a role in the development of MSD. The present clinical and experimental study demonstrated similar interactions between motor co-ordination and neck-shoulder pain in occupational settings. We therefore suggest that this experimental model can be used to study mechanisms related to MSD. Information on such modulatory processes may help in the design of new strategies aimed at reducing the development of MSD.     

Inhibited skeletal muscle healing in cyclooxygenase-2 gene-deficient mice: the role of PGE2 and PGF2alpha.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat skeletal muscle injury. However, studies have shown that NSAIDs may be detrimental to the healing process. Mediated by prostaglandin F(2alpha) (PGF(2alpha)) and prostaglandin E(2) (PGE(2)), the cycloxygenase-2 (COX-2) pathway plays an important role in muscle healing. We hypothesize that the COX-2 pathway is important for the fusion of muscle cells and the regeneration of injured muscle. For the in vitro experiments, we isolated myogenic precursor cells from wild-type (Wt) and COX-2 gene-deficient (COX-2(-/-)) mice and examined the effect of PGE(2) and PGF(2alpha) on cell fusion. For the in vivo experiments, we created laceration injury on the tibialis anterior (TA) muscles of Wt and COX-2(-/-) mice. Five and 14 days after injury, we examined the TA muscles histologically and functionally. We found that the secondary fusion between nascent myotubes and myogenic precursor cells isolated from COX-2(-/-) mice was severely compromised compared with that of Wt controls but was restored by the addition of PGF(2alpha) or, to a lesser extent, PGE(2) to the culture. Histological and functional assessments of the TA muscles in COX-2(-/-) mice revealed decreased regeneration relative to that observed in the Wt mice. The findings reported here demonstrate that the COX-2 pathway plays an important role in muscle healing and that prostaglandins are key mediators of the COX-2 pathway. It suggests that the decision to use NSAIDs to treat muscle injuries warrants critical evaluation because NSAIDs might impair muscle healing by inhibiting the fusion of myogenic precursor cells.     

The patterns of changes in the electromyographic profile of muscles in some gait disorders

Electromyograms (EMGs) of subjects with different gait pathologies have been used to analyze the most typical forms of transformation of the muscle EMG profile: (1) a decrease in the muscle electrical activity during a locomotor cycle, either uniform or with a predominant reduction in the region of maximum values (the Mx zone); the former variant is characteristic of structural damage to nerves and muscles, whereas the latter variant is of functional origin because it is related to the alterations in the biomechanical conditions of muscle work during walking; (2) an increase in muscle electrical activity during the cycle, its maxima being prolonged from the Mx zone to the zone of moderate activity (the Md zone); and (3) a complete shift of the activity peaks to another phase of the cycle, usually from the Mx to the Md zone. It has been assumed that all forms of the transformation of the muscle EMG profile except a drastic uniform decrease in activity on damage to nerve and muscle structures are of afferent origin. These types of alterations in the EMG profile are accounted for by disturbance of the biomechanical conditions of muscle activity, such as an increased or decreased muscle load.     

Transient pain developers show increased abdominal muscle activity during prolonged sitting

BackgroundSitting is a commonly adopted posture during work and prolonged exposures may have detrimental effects. Little attention has been paid to the thoracic spine and/or multiple axes of motion during prolonged sitting. Accordingly, this study examined three-dimensional motion and muscle activity of the trunk during two hours of uninterrupted sitting.MethodsTen asymptomatic males sat during a simulated office task. Kinematics were analyzed from six segments (Neck, Upper-, Mid-, and Lower-thoracic, Lumbar, and Pelvis) and electromyography was recorded from eight muscles bilaterally.ResultsFour participants developed transient pain. These participants showed higher average muscle activations in the abdominal muscles. Additionally, the non-pain group showed less lateral bend positional change in the mid-thoracic region compared to the upper- and lower-thoracic regions. Weak-to-moderate positive correlations were also found between rated pain and low back muscle activation.DiscussionThe results provided further evidence of reduced movement in non-pain developers and altered muscle activation patterns in pain developers. Low-level, prolonged static contractions could lead to an increased risk of injury; and though the increased abdominal activity in the pain developers was not directly associated with increased rated pain scores, this could indicate a pre-disposition to, or enhancer of, transient pain development.     

Systemic administration of IGF-I enhances oxidative status and reduces contraction-induced injury in skeletal muscles of mdx dystrophic mice

The absence of dystrophin and resultant disruption of the dystrophin glycoprotein complex renders skeletal muscles of dystrophic patients and dystrophic mdx mice susceptible to contraction-induced injury. Strategies to reduce contraction-induced injury are of critical importance, because this mode of damage contributes to the etiology of myofiber breakdown in the dystrophic pathology. Transgenic overexpression of insulin-like growth factor-I (IGF-I) causes myofiber hypertrophy, increases force production, and can improve the dystrophic pathology in mdx mice. In contrast, the predominant effect of continuous exogenous administration of IGF-I to mdx mice at a low dose (1.0-1.5 mg.kg(-1).day(-1)) is a shift in muscle phenotype from fast glycolytic toward a more oxidative, fatigue-resistant, slow muscle without alterations in myofiber cross-sectional area, muscle mass, or maximum force-producing capacity. We found that exogenous administration of IGF-I to mdx mice increased myofiber succinate dehydrogenase activity, shifted the overall myosin heavy chain isoform composition toward a slower phenotype, and, most importantly, reduced contraction-induced damage in tibialis anterior muscles. The deficit in force-producing capacity after two damaging lengthening contractions was reduced significantly in tibialis anterior muscles of IGF-I-treated (53 +/- 4%) compared with untreated mdx mice (70 +/- 5%, P < 0.05). The results provide further evidence that IGF-I administration can enhance the functional properties of dystrophic skeletal muscle and, compared with results in transgenic mice or virus-mediated overexpression, highlight the disparities in different models of endocrine factor delivery.     

The effect of postural correction on muscle activation amplitudes recorded from the cervicobrachial region

In clinical practice, postural correction is a common treatment approach for individuals with neck and shoulder pain. As chronic static muscle use is thought to be associated with the onset of some neck and shoulder pain syndromes, it is important to understand the impact a postural correction program might have on muscle activation amplitudes in the neck and shoulder regions. Normalized surface electromyographic data were recorded from the levator scapulae, upper trapezius, supraspinatus, posterior deltoid, masseter, rhomboid major, cervical erector spinae, and sternocleidomastoid muscles of the dominant side of each of eighteen healthy subjects. Subjects performed five repetitions of each of four seated typing postures (habitual, corrected, head-forward and slouched) and four standing postures (habitual, corrected, and head-forward and slouched). Repeated-measures analysis of variance models (α = 0.05) revealed that in sitting postural correction tended to decreased the level of muscle activation required in all muscles studied during seated computer work, however this finding was not statistically significant. Corrected posture in sitting did, however produce a statistically significant reduction in muscle activity compared to forward head posture. Corrected posture in standing required more muscle activity than habitual or forward head posture in the majority of cervicobrachial and jaw muscles, suggesting that a graduated approach to postural correction exercises might be required in order to train the muscles to appropriately withstand the requirements of the task. A surprising finding was that muscle activity levels and postural changes had the largest impact on the masseter muscle, which demonstrated activation levels in the order of 20% maximum voluntary electrical activation.     

Cervical and axioscapular muscle stiffness measured with shear wave elastography: A comparison between different levels of work-related neck disability

Assessing muscle mechanical properties in terms of stiffness may provide important insights into mechanisms underlying work-related neck pain. This study compared stiffness of cervical and axioscapular muscles between 92 participants (sonographers) with no (n = 31), mild (n = 43) or moderate/severe (n = 18) neck disability. It was hypothesized that participants with more severe neck pain and disability would present with altered distribution of stiffness in cervical and axioscapular muscles than those with no disability. Using shear wave elastography, the shear modulus (kPa) of five cervical and six axioscapular muscles or muscle segments were measured in a relaxed seated upright or side-lying position. Muscle activity was measured simultaneously using surface electromyography during the elastography measurements and scapular depression was measured using a measurement tape and inclinometer before the elastography measurements to evaluate their potential confounding influences on shear modulus. Increased shear modulus was found in deeper than superficial cervical muscles and more cranial than caudal axioscapular muscles. However, no differences in shear modulus of the cervical or axioscapular muscles were found between sonographers with varying levels of disability. This study suggests no alterations in stiffness of cervical and axioscapular muscles were associated with work-related neck pain and disability.     

Muscle pain after exercise is linked with an inorganic phosphate increase as shown by31P NMR

³¹P nuclear magnetic resonance (NMR) spectra were obtained from the forearm muscles of 5 subjects before and after performing a muscle stretching (eccentric) exercise routine. Spectra collected before and immediately after exercise showed normal resting phosphorylated metabolite levels and unchanged intracellular pH (pH_i). Measurements made on the day following exercise, when muscular pain was apparent, revealed an elevated inorganic phosphate level. No significant changes in other metabolites or pH_i were detected. This study gives the first indication of biochemical change following a form of exercise that is associated with considerable muscle pain and damage. The findings may help in understanding pathological processes resulting in pain and damage in muscle.     

Clinical spinal instability and low back pain.

Clinical instability is an important cause of low back pain. Although there is some controversy concerning its definition, it is most widely believed that the loss of normal pattern of spinal motion causes pain and/or neurologic dysfunction. The stabilizing system of the spine may be divided into three subsystems: (1) the spinal column; (2) the spinal muscles; and (3) the neural control unit. A large number of biomechanical studies of the spinal column have provided insight into the role of the various components of the spinal column in providing spinal stability. The neutral zone was found to be a more sensitive parameter than the range of motion in documenting the effects of mechanical destabilization of the spine caused by injury and restabilization of the spine by osteophyle formation, fusion or muscle stabilization. Clinical studies indicate that the application of an external fixator to the painful segment of the spine can significantly reduce the pain. Results of an in vitro simulation of the study found that it was most probably the decrease in the neutral zone, which was responsible for pain reduction. A hypothesis relating the neutral zone to pain has been presented. The spinal muscles provide significant stability to the spine as shown by both in vitro experiments and mathematical models. Concerning the role of neuromuscular control system, increased body sway has been found in patients with low back pain, indicating a less efficient muscle control system with decreased ability to provide the needed spinal stability.     

Opportunities for rehabilitation of patients with radiation fibrosis syndrome

This review discusses the pathophysiology, evaluation, and treatment of neuromuscular, musculoskeletal, and functional disorders that can result as late effects of radiation treatment.Although radiation therapy is often an effective method of killing cancer cells, it can also damage nearby blood vessels that nourish the skin, ligaments, tendons, muscles, nerves, bones and lungs. This can result in a progressive condition called radiation fibrosis syndrome (RFS). It is generally a late complication of radiotherapy which may manifest clinically years after treatment. Radiation-induced damage can include “myelo-radiculo-plexo-neuro-myopathy,” causing muscle weakness and dysfunction and contributing to neuromuscular injury.RFS is a serious and lifelong disorder which, nevertheless, may often be decremented when identified and rehabilitated early enough. This medical treatment should be a complex procedure consisting of education, physical therapy, occupational therapy, orthotics as well as medications.     

Cellular-scale transport in deformed skeletal muscle following spinal cord injury

Deep tissue injury (DTI) is a severe pressure ulcer initiating in weight-bearing skeletal muscles. Being common in spinal cord injury (SCI) patients, DTI is associated with mechanical cell damage and ischaemia. Muscle microanatomy in SCI patients is characterised by reduced myofibre sizes and smaller, fewer capillaries. We hypothesise that these changes influence mass transport in SCI muscles, making DTI more probable. Using multiphysics models of microscopic cross-sections through normal and SCI muscles, we studied effects of the following factors on transport of glucose and myoglobin (potential biomarker for early DTI detection): (i) abnormal SCI muscle microanatomy, (ii) large tissue deformations and (iii) ischaemia. We found that the build-up of concentrations of glucose and myoglobin is slower for SCI muscles, which could be explained by the pathological SCI microanatomy. These findings overall suggest that microanatomical changes in muscles post-SCI play an important role in the vulnerability of the SCI patients to DTI.