Utility of exercise testing to assess athletes for post COVID-19 myocarditis.

Purpose: This study assessed a functional protocol to identify myocarditis or myocardial involvement in competitive athletes following SARS-CoV2 infection. Methods: We prospectively evaluated competitive athletes (n = 174) for myocarditis or myocardial involvement using the Multidisciplinary Inquiry of Athletes in Miami (MIAMI) protocol, a median of 18.5 (IQR 16-25) days following diagnosis of COVID-19 infection. The protocol included biomarker analysis, ECG, cardiopulmonary stress echocardiography testing with global longitudinal strain (GLS), and targeted cardiac MRI for athletes with abnormal findings. Patients were followed for median of 148 days. Results: We evaluated 52 females and 122 males, with median age 21 (IQR: 19, 22) years. Five (2.9%) had evidence of myocardial involvement, including definite or probable myocarditis (n = 2). Three of the 5 athletes with myocarditis or myocardial involvement had clinically significant abnormalities during stress testing including ventricular ectopy, wall motion abnormalities and/or elevated VE/VCO2, while the other two athletes had resting ECG abnormalities. VO2max, left ventricular ejection fraction and GLS were similar between those with or without myocardial involvement. No adverse events were reported in the 169 athletes cleared to exercise at a median follow-up of 148 (IQR108,211) days. Patients who were initially restricted from exercise had no adverse sequelae and were cleared to resume training between 3 and 12 months post diagnosis. Conclusions: Screening protocols that include exercise testing may enhance the sensitivity of detecting COVID-19 related myocardial involvement following recovery from SARS-CoV2 infection.

Mechanisms of energy dissipation and relationship with tissue composition in human meniscus.

OBJECTIVE: The human meniscus is essential in maintaining proper knee joint function. The meniscus absorbs shock, distributes loads, and stabilizes the knee joint to prevent the onset of osteoarthritis. The extent of its shock-absorbing role can be estimated by measuring the energy dissipated by the meniscus during cyclic mechanical loading. METHODS: Samples were prepared from the central and horn regions of medial and lateral human menisci from 8 donors (both knees for total of 16 samples). Cyclic compression tests at several compression strains and frequencies yielded the energy dissipated per tissue volume. A GEE regression model was used to investigate the effects of compression, meniscal side and region, and water content on energy dissipation in order to account for repeated measures within samples. RESULTS: Energy dissipation by the meniscus increased with compressive strain from ∼0.1 kJ/m3 (at 10% strain) to ∼10 kJ/m3 (at 20% strain) and decreased with loading frequency. Samples from the anterior region provided the largest energy dissipation when compared to central and posterior samples (P < 0.05). Water content for the 16 meniscal tissues was 77.9 (C.I. 72.0-83.8%) of the total tissue mass. A negative correlation was found between energy dissipation and water content (P < 0.05). CONCLUSION: The extent of energy dissipated by the meniscus is inversely related to loading frequency and meniscal water content.

Applying physical science principles to mid-substance Achilles tendinopathy and the relationship to eccentric lengthening exercises.

Mid-substance Achilles tendinopathy is common in the active population. Eccentric (lengthening) exercises are known to be effective in alleviating the clinical condition. To better understand mid-substance Achilles tendinopathy and the response to lengthening exercises physical science principles of elasticity are applied. We apply elastic motion laws to the spring-like tendon as well as the normal and pathological adaptation seen with this common injury. We will validate important assumptions of the spring-like behavior of the tendon and then apply these findings to the injured and rehabilitating states. Our analysis considers that the tendon can be viewed as being spring-like with elasticity principles being applicable and the force exerted on the tendon during lengthening is primarily in a uniaxial direction. This applied lengthening force results in tendon mechanical and structural adaptation. Injury, and ultimately the clinical condition, occurs when the applied force exceeds the ability of the tendon to normally adapt. Morphological changes of the injured tendon are an attempt by the body to make the tendon more compliant. Lengthening exercises can be assessed as achieving this task with an improvement of tendon compliance. Physical science analysis proposes that the preferred rehabilitation tendon pathway is to try and decrease tendon stiffness to allow for more tendon lengthening. The body's morphological alterations of the pathological tendon are also consistent with this approach. For mid-substance Achilles tendinopathy, this adaptation of decreased stiffness ultimately increases the tendons ability to withstand applied force during lengthening.

Differential knee joint loading patterns during gait for individuals with tibiofemoral and patellofemoral articular cartilage defects in the knee.

OBJECTIVE: To determine compartment-specific loading patterns during gait, quantified as joint reaction forces (JRF), of individuals with knee articular cartilage defects (ACD) compared to healthy controls (HC). METHODS: Individuals with ACDs and HC participated. Individuals with ACDs were divided into groups according to ACD location: PF (only a patellofemoral ACD), TF (only a tibiofemoral ACD), and MIX (both PF and TF ACDs). Participants underwent three-dimensional gait analysis at self-selected speed. TF joint reaction force (TF-JRF) was calculated using inverse dynamics. PF joint reaction force (PF-JRF) was derived from estimated quadriceps force (FQUAD) and knee flexion angle. Primary variables of interest were the PF- and TF-JRF peaks (body weight [×BW]). Related secondary variables (gait speed, quadriceps strength, knee function, activity level) were evaluated as covariates. RESULTS: First peak PF-JRF and TF-JRF were similar in the TF and MIX groups (0.75-1.0 ×BW, P = 0.6-0.9). Both peaks were also similar in the PF and HC groups (1.1-1.3 ×BW, P = 0.7-0.8), and higher than the TF and MIX groups (P = 0.004-0.02). For the second peak PF-JRF, only the HC group was higher than the TF group (P = 0.02). The PF group walked at a similar speed as the HC group; both groups walked faster than the TF and MIX groups (P < 0.001). With gait speed and quadriceps strength as covariates, no differences were observed in JRF peaks. CONCLUSIONS: The results suggest the presence of a TF ACD (TF and MIX groups), but not a PF ACD (PF group), may affect joint loading patterns during walking. Walking slower may be a protective gait modification to reduce load.

Implications of the calf musculature and Achilles tendon architectures for understanding the site of injury.

UNLABELLED: Clinically the sites of Achilles Tendon (AT) overuse conditions can be divided into the tendon mid-portion and osteotendinous attachment. PURPOSE: We propose an anatomical analysis of the triceps surae musculotendon unit that could provide a possible anatomic explanation for these 2 sites of injury. METHOD: Twelve cadavers (age 74±7 years) were studied. In both legs, calf muscles (lateral gastrocnemius (LG), medial gastrocnemius (MG) and soleus) were dissected and their volumes measured. Fine saw cuts were made in the sagittal plane, either side of the midline of the calcaneus. Each strip contained the distal part of the tendon and its insertion, together with the superior tuberosity of the calcaneus. Trabecular architecture was analyzed from X-rays taken with Faxitron radiography. Histological sections of the enthesis and the thickness of the uncalcified fibrocartilage and the subchondral plate were evaluated. A finite element model of tendon coupled to a rupture index was developed to investigate the AT response to mechanical load. RESULTS: Muscle volume was highest for the soleus, followed by the MG, and LG. Within the AT, the soleus fibers occupy the antero-medial parts, the MG fibers form the posterior lateral layer, yet the LG head fibers retain the antero-lateral part. The quantity of bone and the apparent trabecular thickness at the enthesis were greatest in the central part of the enthesis. Thickness of calcified fibrocartilage tissue was significantly greater in the central part than medially (P=0.04) and laterally (P=0.03). Uncalcified fibrocartilage was significantly thicker medially than laterally (P=0.02). Finally, finite element analysis showed that AT mechanical stress increased with muscle load and converged at 4.6-7.9cm of the enthesis. CONCLUSION: Our data suggest that the triceps surae musculotendon unit is composed of anatomically distinct parts that undergo non-uniform mechanical loading. There are two sites where potentially tendon mechanical stress increases, the medial/central portions of the enthesis and the tendon midportion.

Biological and physiological role of reactive oxygen species--the good, the bad and the ugly.

Reactive oxygen species (ROS) are chemically reactive molecules that are naturally produced within biological systems. Research has focused extensively on revealing the multi-faceted and complex roles that ROS play in living tissues. In regard to the good side of ROS, this article explores the effects of ROS on signalling, immune response and other physiological responses. To review the potentially bad side of ROS, we explain the consequences of high concentrations of molecules that lead to the disruption of redox homeostasis, which induces oxidative stress damaging intracellular components. The ugly effects of ROS can be observed in devastating cardiac, pulmonary, neurodegenerative and other disorders. Furthermore, this article covers the regulatory enzymes that mitigate the effects of ROS. Glutathione peroxidase, superoxide dismutase and catalase are discussed in particular detail. The current understanding of ROS is incomplete, and it is imperative that future research be performed to understand the implications of ROS in various therapeutic interventions.

Characterization of reactive oxygen species in diaphragm.

Reactive oxygen species (ROS) exist as natural mediators of metabolism to maintain cellular homeostasis. However, ROS production may significantly increase in response to environmental stressors, resulting in extensive cellular damage. Although several potential sources of increased ROS have been proposed, exact mechanisms of their generation have not been completely elucidated. This is particularly true for diaphragmatic skeletal muscle, the key muscle used for respiration. Several experimental models have focused on detection of ROS generation in rodent diaphragm tissue under stressful conditions, including hypoxia, exercise, and heat, as well as ROS formation in single myofibres. Identification methods include direct detection of ROS with confocal or fluorescent microscopy and indirect detection of ROS through end product analysis. This article explores implications of ROS generation and oxidative stress, and also evaluates potential mechanisms of cellular ROS formation in diaphragmatic skeletal muscle.

Mesenchymal stem-cell potential in cartilage repair: an update.

Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non-operative treatments endeavour to control symptoms and include anti-inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field.

The role of muscle strength & activation patterns in patellofemoral pain.

BACKGROUND: To investigate the extent to which quadriceps muscle activation and strength are responsible for patellofemoral pain. METHODS: A pain on-off switch system synchronized with a force transducer and surface electromyography was utilized on 32 volunteer patellofemoral pain patients during maximal isometric and squat exercises. FINDINGS: There were 26 patients out of the 32 tested who complained of pain during the squat or isometric test, of these 20 subjects presented a significant advantage for the vastus lateralis compared to the vastus medialis obliquis activation and 12 patients had decreased quadriceps strength of the symptomatic compared to the non symptomatic leg. All patients who demonstrated weak vastus medialis obliquis activation during the isometric exercise possessed the same symptoms during the squat. On the other hand, 9 patients who showed diminished vastus medialis obliquis activation during the squat displayed equal activation between the vastus medialis obliquis and the vastus lateralis during the isometric task. With regard to the timing for the onset of muscle activation, there were only 4 patients who had a difference (P=0.03) between the symptomatic (0.042 s) and non-symptomatic legs (0.011 s). INTERPRETATION: Causes for patellofemoral pain vary and are not necessarily a result of quadriceps strength deficit or vastus medialis obliquis activation weakness. Patellofemoral pain patients who possess lower vastus medialis obliquis activation compared to the vastus lateralis do not necessarily have quadriceps weakness while patients presenting with quadriceps strength deficits do not always have an imbalance between vastus medialis obliquis and vastus lateralis activation.

Treatment of proximal hamstring ruptures - a systematic review.

Proximal hamstring ruptures are increasingly treated surgically, despite little high-level supporting evidence. We sought to determine whether there are differences in clinical outcome after surgical vs. non-surgical treatment of proximal hamstring tendinous avulsions/ruptures and acute vs. chronic surgical repair of tendinous avulsions. Multiple medical databases were searched for Level I-IV evidence. 18 studies were included. 298 subjects (300 proximal hamstring injuries) were analyzed with mean age of 39.7 years. 286 injuries were managed with surgical repair vs. 14 non-operative. 95 surgical cases were performed within 4 weeks of the injury (acute), while 191 were performed beyond 4 weeks (chronic). 292 injuries were tendinous avulsions while 8 were bony tuberosity avulsions. Surgical repair resulted in significantly (p < 0.05) better subjective outcomes, greater rate of return to pre-injury level of sport, and greater strength/endurance than non-surgical management. Similarly, acute surgical repair had significantly better patient satisfaction, subjective outcomes, pain relief, strength/endurance, and higher rate of return to pre-injury level of sport than chronic repair (p < 0.001) with reduced risk of complications and re-rupture (p < 0.05). Chronic surgical repair also improves outcomes, strength and endurance, and return-to-sport, but not as well as acute repair. Non-operative treatment results in reduced patient satisfaction, with significantly lower rates of return to pre-injury level of sport and reduced hamstring muscle strength.

Semi-automated segmentation to assess the lateral meniscus in normal and osteoarthritic knees.

OBJECTIVE: The goal of this study was to develop an algorithm to semi-automatically segment the meniscus in a series of magnetic resonance (MR) images to use for normal knees and those with moderate osteoarthritis (OA). METHOD: The segmentation method was developed then evaluated on 10 baseline MR images obtained from subjects with no evidence, symptoms, or risk factors of knee (OA), and 14 from subjects with established knee OA enrolled in the Osteoarthritis Initiative (OAI). After manually choosing a seed point within the meniscus, a threshold level was calculated through a Gaussian fit model. Under anatomical, intensity, and range constraints, a threshold operation was completed followed by conditional dilation and post-processing. The post-processing operation reevaluates the pixels included and excluded in the area surrounding the meniscus to improve accuracy. The developed method was evaluated for both normal and degenerative menisci by comparing the segmentation algorithm results with manual segmentations from five human readers. RESULTS: The semi-automated segmentation method produces results similar to those of trained observers, with an average similarity index over 0.80 for normal participants and 0.75, 0.67, and 0.64 for participants with established knee OA with Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) scores of 0, one, and two respectively. CONCLUSION: The semi-automatic segmentation method produced accurate and consistent segmentations of the meniscus when compared to manual segmentations in the assessment of normal menisci in mild to moderate OA. Future studies will examine the change in volume, thickness, and intensity characteristics at different stages of OA.

A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet-rich plasma.

OBJECTIVE: To appraise existing evidence for prolotherapy, polidocanol, autologous whole blood and platelet-rich plasma injection therapies for lateral epicondylosis (LE). DESIGN: Systematic review. DATA SOURCES: Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine. SEARCH STRATEGY: names and descriptors of the therapies and LE. STUDY SELECTION: All human studies assessing the four therapies for LE. MAIN RESULTS: Results of five prospective case series and four controlled trials (three prolotherapy, two polidocanol, three autologous whole blood and one platelet-rich plasma) suggest each of the four therapies is effective for LE. In follow-up periods ranging from 9 to 108 weeks, studies reported sustained, statistically significant (p<0.05) improvement in visual analogue scale primary outcome pain score measures and disease-specific questionnaires; relative effect sizes ranged from 51% to 94%; Cohen's d ranged from 0.68 to 6.68. Secondary outcomes also improved, including biomechanical elbow function assessment (polidocanol and prolotherapy), presence of abnormalities and increased vascularity on ultrasound (autologous whole blood and polidocanol). Subjects reported satisfaction with therapies on single-item assessments. All studies were limited by small sample size. CONCLUSIONS: There is strong pilot-level evidence supporting the use of prolotherapy, polidocanol, autologous whole blood and platelet-rich plasma injections in the treatment of LE. Rigorous studies of sufficient sample size, assessing these injection therapies using validated clinical, radiological and biomechanical measures, and tissue injury/healing-responsive biomarkers, are needed to determine long-term effectiveness and safety, and whether these techniques can play a definitive role in the management of LE and other tendinopathies.

The practice of primary care sports medicine in the USA.

OBJECTIVE: To investigate and to characterise the practice patterns, academic rank, and income variables that exist in order to better understand the career of a sports medicine physician in the USA. DESIGN: A cross-sectional survey of family physicians holding a Certificate of Added Qualifications in Sports Medicine through the American Board of Family Medicine as of January 2006. RESULTS: The survey was completed by 325 of 862 physicians (a return rate of 38%). Of all respondents, 212 (65%) reported completing a Primary Care Sports Medicine Fellowship, 276 (85%) were male and 49 (15%) were female, and 300 (92%) reported having a MD, while 25 (8%) had a DO. Clinical duties represented the largest proportion of the physicians' schedules (7.94 half days/week), and the majority of physicians performed routine athletic event coverage. The average salary for all physicians was $166,000 US. Higher-income groups included: men ($172,000 vs $132 000 for women); regions including Central, South East, and South West; full professors; and non-student health or urgent care clinical work. With control for all other variables, four groups demonstrated significantly higher odds of being high income earners (annual gross salary > $200,000 US). These groups included age over 40, male sex, practice owner, and seeing over 10 patients per half day. CONCLUSIONS: Salary can be related to age, gender, number of patients seen, and practice ownership. No statistical difference among salaries was found between MDs and DOs, osteopathic manipulative therapy (OMT) practice, region of the country, or how practices are marketed.

Where tendons and ligaments meet bone: attachment sites ('entheses') in relation to exercise and/or mechanical load.

Entheses (insertion sites, osteotendinous junctions, osteoligamentous junctions) are sites of stress concentration at the region where tendons and ligaments attach to bone. Consequently, they are commonly subject to overuse injuries (enthesopathies) that are well documented in a number of sports. In this review, we focus on the structure-function correlations of entheses on both the hard and the soft tissue sides of the junction. Particular attention is paid to mechanical factors that influence form and function and thus to exploring the relationship between entheses and exercise. The molecular parameters indicative of adaptation to mechanical stress are evaluated, and the basis on which entheses are classified is explained. The application of the 'enthesis organ' concept (a collection of tissues adjacent to the enthesis itself, which jointly serve the common function of stress dissipation) to understanding enthesopathies is considered and novel roles of adipose tissue at entheses are reviewed. A distinction is made between different locations of fat at entheses, and possible functions include space-filling and proprioception. The basic anchorage role of entheses is considered in detail and comparisons are explored between entheses and other biological 'anchorage' sites. The ability of entheses for self-repair is emphasized and a range of enthesopathies common in sport are reviewed (e.g. tennis elbow, golfer's elbow, jumper's knee, plantar fasciitis and Achilles insertional tendinopathies). Attention is drawn to the degenerative, rather than inflammatory, nature of most enthesopathies in sport. The biomechanical factors contributing to the development of enthesopathies are reviewed and the importance of considering the muscle-tendon-bone unit as a whole is recognized. Bony spur formation is assessed in relation to other changes at entheses which parallel those in osteoarthritic synovial joints.

Hyperbaric oxygen therapy for delayed onset muscle soreness and closed soft tissue injury.

BACKGROUND: Soft tissue injuries (including muscle damage after unaccustomed exercise) are common and are often associated with athletic activity. Hyperbaric oxygen therapy (HBOT) is the therapeutic administration of 100% oxygen at environmental pressures greater than one atmosphere. OBJECTIVES: To assess the benefits and harms of HBOT for treating soft tissue injury, including delayed onset muscle soreness (DOMS). SEARCH STRATEGY: We searched the following in July 2004: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTIHM and reference lists from relevant articles. Relevant journals were handsearched and researchers in the field contacted. SELECTION CRITERIA: Randomised trials comparing the effect on closed soft tissue injury (including DOMS) of therapeutic regimens which include HBOT with those that exclude HBOT (with or without sham therapy). DATA COLLECTION AND ANALYSIS: Four reviewers independently evaluated study quality and extracted data. Most of the data presented in the review were extracted from graphs in the trial reports. MAIN RESULTS: Nine small trials involving 219 participants were included. Two trials compared HBOT versus sham therapy on acute closed soft tissue injuries (ankle sprain and medial collateral knee ligament injury respectively). The other seven trials examined the effect of HBOT on DOMS following eccentric exercise in unconditioned volunteers. All 32 participants of the ankle sprain trial returned to their normal activities. There were no significant differences between the two groups in time to recovery, functional outcomes, pain, or swelling. There was no difference between the two groups in knee function scores in the second acute injury trial; however, intention-to-treat analysis was not possible for this trial. Pooling of data from the seven DOMS trials showed significantly and consistently higher pain at 48 and 72 hours in the HBOT group (mean difference in pain score at 48 hours [0 to 10 worst pain] 0.88, 95% CI 0.09 to 1.67, P = 0.03) in trials where HBOT was started immediately. There were no differences between the two groups in longer-term pain scores or in any measures of swelling or muscle strength. No trial reported complications of HBOT but careful selection of participants was evident in most trials. AUTHORS' CONCLUSIONS: There was insufficient evidence from comparisons tested within randomised controlled trials to establish the effects of HBOT on ankle sprain or acute knee ligament injury, or on experimentally induced DOMS. There was some evidence that HBOT may increase interim pain in DOMS. Any future use of HBOT for these injuries would need to have been preceded by carefully conducted randomised controlled trials which have demonstrated effectiveness.

Effects of eccentric phase velocity of plyometric training on the vertical jump.

The aim of this study was to compare the effects of plyometric training performed with rapid or slow stretch contraction on jump performance and muscle properties. Thirty males between the ages of 19 and 22 volunteered for the 8-week experiment. Subjects were divided into the following three groups: training group 1 (TG1), training group 2 (TG2), and control group (CG). Each of the two experimental groups underwent a unique training regimen. For the first group (TG1, n = 12): from a standing position the subject flexed his knees to a 90 degrees angle with velocity standardized and controlled at 0.4 m/s and immediately performed a leg extension as quickly as possible. For the second group (TG2, n = 12): from a standing position, the subject flexed his knees to a 90 degrees angle with velocity standardized at 0.2 m/s and then performed a leg extension as quickly as possible. Each exercise consisted of six sets of ten repetitions with a barbell on the shoulders at 70 % of the maximal isometric force (1 RM). The 70 % load was modified at two-week intervals by evaluating a new 1 RM. Exercises were performed four times a week over the eight-week period. The third group (CG, n = 6), served as the control group. Maximal isometric force (MVC), maximal concentric force, squat jump (SJ) and counter movement jump (CMJ) exercises were performed before and after the training program. Subjects were filmed (100 Hz) and each jump was divided into three phases: eccentric phase (ECC), transition phase (TR) and concentric phase (CON). Surface EMG was used to determine the changes in the electromyographic (EMG) activity before and after the training program. There was an increase in leg extension force, velocity and electrical activity for SJ and CMJ for the two training groups (p < 0.05). However, TG1 showed a significant advantage in CMJ performance as well as a significant decrease in TR compared to the TG2 (p < 0.05). The results of this study show that when plyometric training is performed with rapid stretch contraction the CMJ jump height increases and the TR decreases.

The inflammatory response: friend or enemy for muscle injury?

Limiting certain aspects of inflammation may be a useful new treatment for sport related muscle injury.

M1/70 attenuates blood-borne neutrophil oxidants, activation, and myofiber damage following stretch injury.

The purpose of this study was to determine the role of the CD11b-dependent respiratory burst in neutrophil oxidant generation and activation, interleukin-8 (IL-8) production, and myofiber damage after muscle stretch injury by using the monoclonal antibody M1/70 to block this pathway. Twelve male New Zealand White rabbits were randomly assigned to a treatment group: M1/70 (n = 6), IgG isotype control (n = 3), or saline control (n = 3). After intravenous injection of the assigned agent under gas anesthesia, a standardized single-stretch injury was created in the right tibialis anterior, whereas the left tibialis anterior underwent a sham surgery. Blood-borne neutrophil oxidant generation and CD11b receptor density and plasma IL-8 levels were measured pre- and 24 h postinjury. Damage was assessed histologically at the hematoma site by counting torn myofibers. M1/70 group demonstrated decreased blood-borne neutrophil oxidant generation (P < 0.05) and CD11b receptor density (P < 0.05), an increase in plasma IL-8 concentration (P < 0.01), and less torn myofibers (P < 0.01) compared with IgG isotype or saline control groups. These data indicate that 1). CD11b-dependent respiratory burst is a major source of oxidants produced by the neutrophil, and that treatment with M1/70 2). attenuates neutrophil activation status, 3). increases plasma IL-8 concentration, and 4). minimizes myofiber damage 24 h postmuscle stretch injury.

Oxidant production and immune response after stretch injury in skeletal muscle.

PURPOSE: This study investigated oxidant production and associated immune response after acute muscle stretch injury. METHODS: A standardized single stretch injury was performed on the tibialis anterior (TA) muscle of 36 male New Zealand white rabbits while contralateral control limbs underwent a sham surgery. Animals were sacrificed 0, 4, 12, 24, 48, and 72 h after injury. Potential sites of oxidant production, measured with a dichlorofluorescein (DCF) probe, were evaluated using two separate buffers. RESULTS: Nonmitochondrial oxidant production measured under basal buffer conditions (0.1 M potassium phosphate) was increased in both injured and control limbs at 24 h (P < 0.01) and was greater in the injured limb at 12 and 48 h (P < 0.01). There was also an interaction of time and injury (P < 0.05). Maximum oxidant production by neutrophils and macrophages, stimulated by the induced buffer (including 1.7 mM ADP, 0.1 mM NADPH, 0.1 mM FeCl3), was increased in both injured and control limbs at 4 h (P < 0.01) and was greater in the injured limb at 48 h (P < 0.01). Myeloperoxidase (MPO) activity, indicating the presence of activated neutrophils, was higher in the injured limb at 4 and 48 h (P < 0.01). The activities of superoxide radical producing and quenching enzymes, xanthine oxidase (XO) and superoxide dismutase (SOD), were elevated at 24 (P < 0.01) and 4 h (P < 0.05), respectively, but showed no difference between injured and control limbs. CONCLUSION: We conclude that acute muscle stretch injury and the required surgeries to generate the injury result in a biphasic increase in oxidant production in both injured and control limbs, suggesting a systemic immune response. The increase in oxidant production at 4 h may be caused by an increase in activated neutrophils, whereas XO activity may contribute to oxidant generation at 24 h.

Analysis of changes in mRNA levels of myoblast- and fibroblast-derived gene products in healing skeletal muscle using quantitative reverse transcription-polymerase chain reaction.

Changes in expression of type III alpha1-collagen and myosin II heavy chains were characterized in rabbit skeletal muscle following single stretch injury using quantitative reverse transcription-polymerase chain reaction. Collagen III expression was highly elevated in the injured leg compared with the control limb both at the myotendinous junction and in the distal muscle belly. While upregulation of collagen III expression at the myotendinous junction was maximal on day 1, collagen III expression in the distal muscle belly was unchanged on day 1 but highly elevated by day 3. Over the initial 7-day period, there was on average a 94% increase in collagen III expression at the myotendinous junction and a 42% increase in the distal muscle belly. On the other hand, there was little difference, in fact, slightly less expression of myosin II isoforms, in the injured leg compared with the control side. Immunohistochemical analysis of injured muscle showed significant collagen III deposition at the myotendinous junction beginning at day 3 post-injury and still evident by day 14. Focal deposits of type I and III collagen were first apparent in the distal muscle belly by day 3 and striking by day 7. Taken together, the data suggest the formation of connective tissue scar at the injury site and the absence of significant muscle regeneration following muscle stretch. Furthermore, microinjuries distant to the primary site of injury may result in more general muscle fibrosis and scarring.