Christer Malm

Immunological changes in human skeletal muscle and blood after eccentric exercise and multiple biopsies.

1 A role of the immune system in muscular adaptation to physical exercise has been suggested but data from controlled human studies are scarce. The present study investigated immunological events in human blood and skeletal muscle by immunohistochemistry and flow cytometry after eccentric cycling exercise and multiple biopsies. 2 Immunohistochemical detection of neutrophil‐ (CD11b, CD15), macrophage‐ (CD163), satellite cell‐ (CD56) and IL‐1β‐specific antigens increased similarly in human skeletal muscle after eccentric cycling exercise together with multiple muscle biopsies, or multiple biopsies only. 3 Changes in immunological variables in blood and muscle were related, and monocytes and natural killer (NK) cells appeared to have governing functions over immunological events in human skeletal muscle. 4 Delayed onset muscle soreness, serum creatine kinase activity and C‐reactive protein concentration were not related to leukocyte infiltration in human skeletal muscle. 5 Eccentric cycling and/or muscle biopsies did not result in T cell infiltration in human skeletal muscle. Modes of stress other than eccentric cycling should therefore be evaluated as a myositis model in human. 6 Based on results from the present study, and in the light of previously published data, it appears plausible that muscular adaptation to physical exercise occurs without preceding muscle inflammation. Nevertheless, leukocytes seem important for repair, regeneration and adaptation of human skeletal muscle.

Leukocytes, cytokines, growth factors and hormones in human skeletal muscle and blood after uphill or downhill running

Muscular adaptation to physical exercise has previously been described as a repair process following tissue damage. Recently, evidence has been published to question this hypothesis. The purpose of this study was to investigate inflammatory processes in human skeletal muscle and epimysium after acute physical exercise with large eccentric components. Three groups of subjects (n= 19) performed 45 min treadmill running at either 4 deg (n= 5) or 8 deg (n= 9) downhill or 4 deg uphill (n= 5) and one group served as control (n= 9). One biopsy was taken from each subject 48 h post exercise. Blood samples were taken up to 7 days post exercise. Compared to the control group, none of the markers of inflammation in muscle and epimysium samples was different in any exercised group. Only subjects in the Downhill groups experienced delayed onset of muscle soreness (DOMS) and increased serum creatine kinase activity (CK). The detected levels of immunohistochemical markers for T cells (CD3), granulocytes (CD11b), leukaemia inhibitory factor (LIF) and hypoxia‐inducible factor 1β (HIF‐1β) were greater in epimysium from exercised subjects with DOMS ratings >3 (0–10 scale) compared to exercised subjects without DOMS but not higher than controls. Eccentric physical exercise (downhill running) did not result in skeletal muscle inflammation 48 h post exercise, despite DOMS and increased CK. It is suggested that exercise can induce DOMS by activating inflammatory factors present in the epimysium before exercise. Repeated physical training may alter the content of inflammatory factors in the epimysium and thus reduce DOMS.

Eccentric contractions leading to DOMS do not cause loss of desmin nor fibre necrosis in human muscle

Abstract. High force eccentric muscle contractions can result in delayed onset muscle soreness (DOMS), prolonged loss of muscle strength, decreased range of motion, muscle swelling and an increase of muscle proteins in the blood. At the ultrastructural level Z-line streaming and myofibrillar disruptions have been taken as evidence for muscle damage. In animal models of eccentric exercise-induced injury, disruption of the cytoskeleton and the sarcolemma of muscle fibres occurs within the first hour after the exercise, since a rapid loss of staining of desmin, a cytoskeletal protein, and the presence of fibronectin, a plasma and extracellular protein, are observed within the muscle fibres. In the present study, biopsies from subjects who had performed different eccentric exercises and had developed DOMS were examined. Our aim was to determine whether eccentric exercise leading to DOMS causes sarcolemmal disruption and loss of desmin in humans. Our study shows that even though the subjects had DOMS, muscle fibres had neither lost staining for desmin nor contained plasma fibronectin. This study therefore does not support previous conclusions that there is muscle fibre degeneration and necrosis in human skeletal muscle after eccentric exercise leading to DOMS. Our data are in agreement with the recent findings that there is no inflammatory response in skeletal muscle following eccentric exercise in humans. In combination, these findings should stimulate the search for other mechanisms explaining the functional and structural alterations in human skeletal muscle after eccentric exercise.

Skeletal muscle morphology in power-lifters with and without anabolic steroids

The morphological appearance of the vastus lateralis (VL) muscle from high-level power-lifters on long-term anabolic steroid supplementation (PAS) and power-lifters never taking anabolic steroids (P) was compared. The effects of long- and short-term supplementation were compared. Enzyme-immunohistochemical investigations were performed to assess muscle fiber type composition, fiber area, number of myonuclei per fiber, internal myonuclei, myonuclear domains and proportion of satellite cells. The PAS group had larger type I, IIA, IIAB and IIC fiber areas (p<0.05). The number of myonuclei/fiber and the proportion of central nuclei were significantly higher in the PAS group (p<0.05). Similar results were seen in the trapezius muscle (T) but additionally, in T the proportion of fibers expressing developmental myosin isoforms was higher in the PAS group compared to the P group. Further, in VL, the PAS group had significantly larger nuclear domains in fibers containing ≥5 myonuclei. The results of AS on VL morphology in this study were similar to previously reported short-term effects of AS on VL. The initial effects from AS appear to be maintained for several years.

Effect of eccentric exercise on muscle oxidative metabolism in humans.

PURPOSE The purpose of this study was to evaluate the effects of eccentric exercise on muscle oxidative function. METHODS Thirteen subjects performed high-intensity eccentric cycling for 30 min. Muscle oxidative function in vastus lateralis was evaluated by measurements of respiration in permeabilized muscle fibers (skinned fibers) and from the kinetics of oxyhemoglobin (oxyHb) saturation measured with near infrared spectroscopy (NIRS). RESULTS After eccentric cycling, all subjects reported extensive delayed onset muscle soreness (DOMS), but plasma markers of muscle damage (creatine kinase and beta-glucuronidase activity) were not significantly altered. The half time of oxyHb desaturation after circulatory occlusion (128 +/- 11 s, mean +/- SE) and oxyHb resaturation after restoration of blood flow (13.8 +/- 0.7 s) were not significantly changed after eccentric cycling (N = 7). Respiration in skinned muscle fibers measured in the absence of ADP and in the presence of a submaximal (0.1 mM) or maximal ADP concentration (1 mM) was not significantly changed after eccentric cycling (N = 6). The sensitivity of respiration to ADP was not significantly changed after eccentric cycling. CONCLUSIONS Muscle oxidative function (maximal respiration and respiratory control by ADP) was not compromised after high-intensity eccentric cycle exercise. Furthermore, NIRS indicates that after eccentric cycling muscle oxygen utilization and local oxygen transport at rest are unchanged. It is concluded that eccentric cycling, although causing DOMS, does not negatively affect skeletal muscle oxidative function.

Exercise immunology: the current state of man and mouse.

The mechanisms governing the body’s response to physical exercise have been investigated from various perspectives including metabolism, nutrition, age and sex. Increased attention to the immune system during recent decades is reflected by a rapidly growing number of publications in the field. This article highlights the most recent findings and only briefly summarises more basic concepts already reviewed by others. Topics include Th1/Th2 cytokine balance, inoculation time, age and immune compensation. Some less investigated areas are discussed including studies in children, the environment and dendritic cells.Because physical exercise enhances some aspects and suppresses other aspects of immunity, the biological significance of alterations in the immune system are unknown. So far, no link between immunological alterations and infection rate has been established and infection after strenuous physical exercise is equally likely to be the result of exercising with an already established rather than a new infection. If there is an increased risk for infections with increased exercise duration and intensity, why do overtrained athletes not display the greatest risk for upper respiratory tract infections? Increased knowledge on immune system modulations with physical exercise is relevant both from a public health and elite athlete’s point of view.

Infectious episodes before and after a marathon race.

The aim of this study was to investigate the incidence of self‐reported infectious episodes (IE) during 3 weeks before (pre‐IE) and 3 weeks after (post‐IE) a marathon race and relate these figures to training status, running time, socioeconomic and demographic factors. Two questionnaires, including questions about important factors for IE incidence, were given to a representative cohort of 1694 runners (17% of all finishers) in the Stockholm Marathon 2000.

Susceptibility to infections in elite athletes: the S-curve

The susceptibility to upper respiratory tract infections (URTIs) after physical exercise has been described with a J‐shaped curve, suggesting protection from infections with moderate exercise and increased risk for URTIs in elite athletes. Several factors such as time of inoculation, previous infections, pathogen exposure, other stressors than exercise etc. can influence infection outcome. Observed infections in athletes can, therefore, be either the result of increased susceptibility to a novel pathogen, or more severe symptoms of an already established infection. Moreover, the definitions of “strenuous” exercise and “elite” athletes are equivocal, making comparisons between studies difficult.

Transfusion of cryopreserved human red blood cells into healthy humans is associated with rapid extravascular hemolysis without a proinflammatory cytokine response

BACKGROUND: Transfusion of stored red blood cells (RBCs) can be associated with adverse side effects. Recent studies in mice transfused with stored RBCs showed that a strong proinflammatory cytokine storm was induced due to extravascular hemolysis already at 2 hours after transfusion. Therefore, we here investigated if transfusion of 2 units of cryopreserved autologous RBCs induced a proinflammatory response in healthy human volunteers.

Validation of physiological tests in relation to competitive performances in elite male distance cross-country skiing

Abstract Carlsson, M, Carlsson, T, Hammarström, D, Tiivel, T, Malm, C, and Tonkonogi, M. Validation of physiological tests in relation to competitive performances in elite male distance cross-country skiing. J Strength Cond Res 26(6): 1496–1504, 2012—The purpose of the present study was to establish which physiological test parameters reflects the distance performances in the Swedish National Championships in cross-country skiing (SNC) and the International Ski Federations ranking points for distance performances (FISdist). The present study also aimed to create multiple regression models to describe skiing performance for the SNC distance races and International Ski Federations (FIS) ranking. Twelve male, Swedish, national elite, cross-country skiers (maximal oxygen consumption [V[Combining Dot Above]O2max] = 5.34 ± 0.34 L·min−1) volunteered to participate in the study. Their results in the 2008 SNC (15 km race [SNC15] and 30 km race [SNC30]) and FISdist points were used as performance data. On the week preceding the Championship, subjects completed a test battery consisting of 7 physiological tests: isokinetic knee extension peak torque (PT), vertical jumps (VJ), lactate threshold (LT), V[Combining Dot Above]O2max, and 3 double poling tests of different durations (DP20, DP60, and DP360). Correlations were established using Pearsons correlation analysis, and models to describe skiing performance were created using standard multiple linear regression analysis. Significant correlations were found between the performance parameters and test parameters derived from LT, V[Combining Dot Above]O2max, and DP60 tests. No correlations with any performance parameter were found for PT, VJ, DP20, and DP360 tests. For FISdist and SNC15, the models explain 81% and 78% of the variance in performance, respectively. No statistically valid regression model was found for SNC30. The results of this study imply that the physiological demands in male elite distance cross-country skiing performances are different in different events. To adequately evaluate a skiers performance ability in distance cross-country skiing, it is necessary to use test parameters and regression models that reflect the specific performance.