Cited by 319Exercise and Physiological ResponsesMuscle Physiology and DisordersMuscle metabolism and nutrition

Myofibre damage in human skeletal muscle: effects of electrical stimulation versus voluntary contraction

Open access
Crameri, R. M., Aagaard, P., Qvortrup, K., Langberg, H., Olesen, J., Kjær, M.·2007·The Journal of Physiology

Abstract

Disruption to proteins within the myofibre after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation but not in humans using voluntary exercise. Untrained males ( n = 8, range 22–27 years) performed 210 maximal eccentric contractions with each leg on an isokinetic dynamometer, voluntarily (VOL) with one leg and electrically induced (ES) with the other leg. Assessments from the skeletal muscle were obtained prior to exercise and at 5, 24, 96 and 192 h postexercise. Muscle tenderness rose in VOL and ES after 24 h, and did not differ between groups. Maximal isometric contraction strength, rate of force development and impulse declined in the VOL leg from 4 h after exercise, but not in ES (except at 24 h). In contrast, a significant disruption of cytoskeletal proteins (desmin) and a rise of myogenic growth factors (myogenin) occurred only in ES. Intracellular disruption and destroyed Z‐lines were markedly more pronounced in ES (40%) compared with VOL (10%). Likewise, the increase in satellite cell markers [neural cell adhesion molecule (N‐CAM) and paired‐box transcription factor (Pax‐7)] was more pronounced in ES versus VOL. Finally, staining of the intramuscular connective tissue (tenascin C) was increased equally in ES and VOL after exercise. The present study demonstrates that in human muscle, the delayed onset of muscle soreness was not significantly different between the two treatments despite marked differences in intramuscular histological markers, in particular myofibre proteins and satellite cell markers. An increase in tenascin C expression in the midbelly of the skeletal muscle in both legs provides further evidence of a potential role for the extracellular matrix in the phenomenon of delayed onset of muscle soreness.

Integrity signals

Registry

Crossref · 10.1113/jphysiol.2007.128827

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 29 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Tenascin C immunoreactivity in total muscle area significantly increased in both legs from 24 h postexercise.

    “The percentage of the total muscle area immunoreactive for tenascin C was significantly increased (VOL, 2.0% and ES, 1.4%) in both legs from 24 h postexercise.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • Findingown data

    The ES leg showed significant increases in desmin-negative, dystrophin-negative, and vimentin-positive myofibres.

    “In contrast, the stimulated leg showed gross myofibre protein changes, with significant increases in desmin-negative, dystrophin-negative and vimentin-positive myofibres.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • Findingown data

    The ES leg demonstrated a significant increase in myogenin expression at 192 h compared with baseline and the corresponding VOL time point.

    “In contrast, the ES leg demonstrated a significant increase in myogenin expression at 192 h postexercise when compared with the baseline sample and the corresponding time point in the VOL leg (Fig. 12).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • Findingown data

    In ES, fully destroyed Z-lines were significantly greater at 24 and 96 h compared with baseline and VOL.

    “the percentage of fully destroyed Z-lines in the ES leg was significantly greater at 24 and 96 h postexercise when compared with baseline and the VOL leg (Fig. 5C).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • Findingown data

    N-CAM positive cells significantly increased at 96 and 192 h postexercise in both legs.

    “A significant increase in cells positive for N-CAM was found in the histological sections taken from all subjects, at 96 and 192 h postexercise in both legs (Fig. 10).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims. 41
  • Classified as probably not a substantial claim. 12
  • The quote only partly states this claim. 1
  • May combine two claims.

    Findingown data

    RFD100 was suppressed at 4, 24, and 96 h in VOL, with no change in ES.

    “Likewise, RFD 100 was suppressed at 4, 24 and 96 h in VOL, with no change in ES (Table 2 and Fig. 4).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    In VOL, disrupted Z-lines significantly increased at 5 and 24 h, and fully destroyed Z-lines increased slightly at 24 h.

    “There was a corresponding significant increase in the percentage of Z-lines disrupted at 5 and 24 h postexercise (Fig. 5B) and a small but significant increase in fully destroyed Z-lines at 24 h postexercise (Fig. 5C).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    MVC remained unchanged in ES except at 24 h, when it decreased by 13.3%.

    “In contrast, MVC remained unchanged in the ES leg, except at 24 h, when MVC decreased by 13.3% in ES (Table 2 and Fig. 4).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    RFD50 was reduced by 20% and 45% at 4 and 24 h in VOL, but unaffected in ES.

    “Rapid muscle force capacity (RFD 50 ) was 20 and 45% reduced at 4 and 24 h in VOL, respectively, but unaffected in ES (Table 2 and Fig. 4).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    Indications from both staining techniques suggested preferential type II fibre disruption, but this could not be confirmed.

    “Indications from both staining techniques did suggest a preferential type II fibre disruption, but this cannot be confirmed.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Quadriceps moment, power, and work during eccentric contractions were substantially greater in VOL than ES.

    “Quadriceps knee extension moment of force (peak moment, average moment in total range of motion), power (peak power, mean power) and contractile work during the 210 eccentric loading contractions were substantially greater for the voluntarily activated leg (VOL) than the electrostimulated leg (ES; P < 0.0001; Table 1).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    In ES, disrupted Z-lines were significantly higher at 24 and 96 h compared with baseline, and at 96 h compared with VOL.

    “The percentage of disrupted Z-lines was significantly higher at 24 and 96 h postexercise when compared with baseline and at 96 h postexercise when compared with the VOL leg (Fig. 5B).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    At fast contraction speed, ES moment, power, and work were 14-27%, 19-27%, and 16-17% of VOL, respectively.

    “When all eccentric loading trials at fast speed (180 deg s -1 ) were averaged, quadriceps moment, power and work in ES amounted to 14-27, 19-27 and 16-17%, respectively, of that generated during VOL (Table 1).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    In ES, intact Z-lines significantly decreased at 5, 24, and 96 h compared with baseline, and at 96 h compared with VOL.

    “In the ES leg, there was a significant decrease in intact Z-lines at 5, 24 and 96 h postexercise when compared with baseline and at 96 h when compared with the VOL leg (Fig. 5A).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    Myofibre necrosis was evident in ES but not VOL, reflected by increased CD68+ macrophages within desmin-negative myofibres in ES.

    “In addition, myofibre necrosis was evident in the ES leg but not in the VOL leg, as reflected by an increase in CD68+ reactive macrophages within the desmin-negative myofibres of the ES leg (data not shown).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    No desmin-negative, dystrophin-negative, or vimentin-positive myofibres were evident in VOL at any time point.

    “No evidence of desmin-negative, dystrophin-negative or vimentin-positive myofibres was evident in the voluntarily activated leg at any time point tested (Figs 7 and 8).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    Relative RFD remained unchanged in ES except at 96 h, when it increased by about 10%.

    “In contrast, relative RFD remained unchanged in ES except at 96 h, when it increased (by ∼10%).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    In VOL, IMP50 was reduced by 25% and 40% at 4 and 24 h, and IMP100 was reduced at 24 h.

    “In the VOL leg, the magnitude of contractile impulse in the most initial contraction phase (IMP 50 ) was 25 and 40% reduced at 4 and 24 h (Table 2), respectively, and also reduced at 24 h when the latter phase of rising muscle force (IMP 100 ) was included (Table 2).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Two individuals showed tenascin C staining as early as 5 h postexercise in the VOL leg.

    “Interestingly, two individuals showed tenascin C staining as early as 5 h postexercise in the VOL leg.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    At slow contraction speed, ES moment, power, and work were 11-13%, 6-13%, and 11-12% of VOL, respectively.

    “When all eccentric loading trials at slow speed (30 deg s -1 ) were averaged, quadriceps moment, power and work in ES amounted to 11-13, 6-13 and 11-12%, respectively, of that generated during VOL (Table 1).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
  • May combine two claims.

    Findingown data

    In the electrically stimulated human vastus lateralis, 13.7 ± 4.5% of myofibres were desmin negative, with the peak at 192 h postexercise.

    “electrically in the present study, 13.7 ± 4.5% of the myofibres were desmin negative, with the peak observed at 192 h postexercise.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In two subjects, detection of tenascin C was seen as early as 5 h postexercise, with the significant increase in expression commencing 24 h after the exercise bout.

    “Furthermore, in two subjects, detection of tenascin C was seen as early as 5 h postexercise, with the significant increase in expression commencing 24 h after the exercise bout.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    At 192 h postexercise following ES, 22% of satellite cells expressed N-CAM, 7% expressed Pax-7, and 14% expressed myogenin.

    “Of interest is the number of satellite cells at 192 h postexercise following ES that expressed the different satellite cell markers: 22% expressed N-CAM; 7% Pax-7; and 14% expressed myogenin.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Disruptions to the ECM were noted in this study, as evidenced by an increase in the number of CD68+ immunoreactive macrophages in the ECM in both legs, with a slightly higher response in the VOL muscle at 24 h postexercise.

    “Disruptions to the ECM were noted in this study, as evidenced by an increase the number of CD68+ immunoreactive macrophages in the ECM in both legs, with a slightly higher response seen in the VOL muscle at 24 h postexercise.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Mechanical muscle function was markedly impaired in response to eccentric voluntary contractions, while electrical stimulation only affected the relative MVC measurements.

    “Mechanical muscle function was markedly impaired in response to the eccentric voluntary contractions, while electrical stimulation only affected the relative MVC measurements.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In the present study, despite gross morphological changes only being present within the myofibres of the electrically stimulated leg, the ectopic tenascin C immunoreactivity increased to a similar extent in muscle biopsies taken from both legs.

    “Interestingly, in the present study, despite gross morphological changes only being present within the myofibres of the electrically stimulated leg, the ectopic tenascin C immunoreactivity increased to a similar extent in muscle biopsies taken from both legs.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Figure 2: No significant difference was found between the two treatments in muscle tenderness; however, a significant time effect was noted.

    “No significant difference was found between the two treatments; however, a significant time effect was noted (P < 0.05).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    The leg activated with electrical stimulation exhibited dramatic myofibre necrosis accompanied by a significant increase in mononuclear cells lying in the satellite cell position that expressed N-CAM and Pax-7 at 96 h postexercise, while all satellite cell markers (N-CAM, Pax-7 and myogenin) were increased at 192 h postexercise.

    “In contrast, the leg that was activated with electrical stimulation exhibited dramatic myofibre necrosis accompanied by a significant increase in mononuclear cells lying in the satellite cell position that expressed N-CAM and Pax-7 at 96 h postexercise, while all satellite cell markers (N-CAM, Pax-7 and myogenin) were increased 192 h postexercise.”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim.

    Findingown data

    Figure 9: No significant difference was noted between the two groups in tenascin C immunoreactivity.

    “No significant difference was noted between the two groups.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    A loss of cell integrity did not occur and an inflammatory cell invasion was not evident in the VOL muscle.

    “Most importantly, a loss of cell integrity did not occur and an inflammatory cell invasion was not evident.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Animal studies may not correlate well to human studies because the amount of exercise is typically more severe in animal studies.

    “It has previously been suggested that animal studies may not correlate well to those in humans, since the amount of exercise is typically more severe than that seen in human studies (Wackerhage, 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wackerhage, 2003

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Electrical stimulation either reverses the recruitment pattern of myofibre types or produces non-selective, spatially fixed, and temporally synchronous stimulation of myofibres.

    “It is believed that electrical stimulation either reverses the recruitment pattern of the myofibre types or produces a non-selective, spatially fixed and temporally synchronous stimulation of the myofibres (Kim et al. 1995;Gregory & Bickel, 2005).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Kim et al. 1995 source

      Not checked in the free run.

    • cites Gregory & Bickel, 2005

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The fibre type of disrupted fibres could not be accurately determined because staining was inconsistent with myosin ATPase and epitope integrity was uncertain.

    “Unfortunately, the staining within the disrupted fibres was not consistent with the myosin ATPase stain to enable the affected fibre to be classified, and we were not confident that the epitope was intact to enable accurate determination of the fibre type through immunohistochemistry.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationreasoning

    The overall contractile capacity of the quadriceps probably was more severely affected in the VOL leg compared with the ES leg, and therefore the decrements during the maximal voluntary test contractions were most compromised in that leg.

    “This means that the overall contractile capacity of the quadriceps probably was more severely affected in the VOL leg compared with the ES leg, and therefore the decrements during the maximal voluntary test contractions were most compromised in that leg.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Bradykinin and other inflammatory mediators can interact with nociceptors in the muscle to trigger the pain response.

    “It is known that bradykinin and other inflammatory mediators can interact with nociceptors in the muscle to trigger the pain response (Graven-Nielsen & Mense, 2001;Rosendal et al. 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Graven-Nielsen & Mense, 2001;Rosendal et al. 2005

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There is a significant increase in blood and interstitial bradykinin and/or prostaglandin in human skeletal muscle and the Achilles tendon early after a single bout of exercise.

    “Previous reports has shown a significant increase in blood and interstitial bradykinin and/or prostaglandin in human skeletal muscle and the Achilles tendon early after a single bout of exercise (Blais et al. 1999;Langberg et al. 2002Langberg et al. , 2003)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Blais et al. 1999;Langberg et al. 2002Langberg et al. , 2003

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    All muscle groups responsible for a lower limb eccentric contraction would have been activated in the VOL exercise conditions and would therefore have experienced DOMS.

    “All muscle groups responsible for a lower limb eccentric contraction would have been activated in the VOL exercise conditions and would therefore have experienced DOMS.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Tenascin C is an adhesion-modulating ECM molecule that is not normally produced by fibroblasts in the endomysium along muscle fibres, except for those fibres close to the myotendinous junction.

    “Tenascin C is an adhesion-modulating ECM molecule that is not normally produced by fibroblasts in the endomysium along muscle fibres, except for those fibres close to the myotendinous junction (Järvinen et al. 1999(Järvinen et al. , 2000)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Järvinen et al. 1999(Järvinen et al. , 2000) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The voluntary exercise represents the physiological responses of skeletal muscle in the lower limb to high-intensity eccentric exercise, whereas electrical stimulation results in muscle fibre necrosis and subsequent regeneration of that tissue.

    “The voluntary exercise therefore represents the physiological responses of skeletal muscle in the lower limb to high-intensity eccentric exercise, whereas electrical stimulation results in muscle fibre necrosis and subsequent regeneration of that tissue.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Pax-7 and N-CAM are expressed in activated satellite cells; Pax-7 appears to be switched off in satellite cells that continue through to terminal differentiation.

    “The Pax-7 and N-CAM are expressed in activated SC; however, the Pax-7 appears to be switched off in the satellite cells that continue through to terminal differentiation (MPC).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zammit et al. (2004)

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The preferential decrease in rapid muscle force characteristics (RFD, impulse) suggests that the stiffness of cellular mechanotransduction pathways (serial and/or lateral) was reduced following the eccentric exercise, possibly owing to changes in cytoskeletal integrity.

    “This preferential decrease in rapid muscle force characteristics (RFD, impulse) further suggests that the stiffness of cellular mechanotransduction pathways (serial and/or lateral) was reduced following the eccentric exercise, possibly owing to changes in cytoskeletal integrity (discussed above).”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Interpretationreasoning

    Eccentric contractions induced tears within the ECM, resulting in an increase in interstitial inflammatory mediators that triggered the nociceptor response within the muscle.

    “We hypothesize that the eccentric contractions induced tears within the ECM and resulted in an increase in interstitial inflammatory mediators and that these triggered the nociceptor response within the muscle.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    In the rat tibialis anterior, 1.7% of fibres were desmin negative and the peak was at 12 h postexercise.

    “In contrast, the tibialis anterior of the rat showed 1.7% desmin-negative fibres and the peak was 12 h postexercise.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Barash et al. 2002;Peters et al. 2003

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The Z-line disruption occurred earlier than previously reported by Yu et al. (2004), most likely due to different collection times used in the two studies.

    “The disruption in the Z-lines did occur earlier than previously reported by Yu et al. (2004); however, this is most likely due to the different collection times used in both studies.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Yu et al. (2004)

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Only those muscles lying under the electrodes would have been contracted during the ES exercise, thus sparing other muscle groups from DOMS and enabling them to participate fully in the mechanical tests postexercise.

    “However, only those muscles lying under the electrodes would have been contracted during the ES exercise, thus sparing other muscle groups from DOMS and enabling them to participate fully in the mechanical tests postexercise.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A single bout of high-intensity exercise was sufficient to increase the number of satellite cells expressing both N-CAM and fetal antigen 1 proteins, but myogenin expression remained unchanged.

    “Previously, we have shown that a single bout of high-intensity exercise was sufficient to increase the number of satellite cells expressing both N-CAM and the fetal antigen 1 proteins but that myogenin expression remained unchanged (Crameri et al. 2004b).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Crameri et al. 2004b

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The growth factors Myf5, MyoD, myogenin and Mrf4 are expressed at varying stages throughout the activation and differentiation cycle.

    “The growth factors myogenic factor 5 (Myf5), MyoD, myogenin and myogenic regulatory factor 4 (Mrf4) are then expressed at varying stages throughout the activation and differentiation cycle as depicted.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zammit et al. (2004)

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    If electrical stimulation causes early activation of type IIX fibres, there is greater potential for myofibre damage, as seen in the ES biopsies of this study.

    “Therefore, if the recruitment pattern during the electrical stimulation causes an early activation of type IIX fibres there is a greater potential for myofibre damage, as was seen in the present study in the ES muscle biopsies.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The difference in myofibre damage between ES and VOL is due to differences in muscle activation pattern rather than the large difference in mechanical force or work between the two modes.
  • Classified as probably not a substantial claim.

    Premisecitation

    Tenascin C expression in skeletal muscle is regulated by mechanical stress, inflammation, or a combination of the two.

    “It has been shown that tenascin C expression in skeletal muscle is regulated by mechanical stress, inflammation, or a combination of the two (Mackie et al. 1988;Mackie & Tucker, 1999;Järvinen et al. 2000Järvinen et al. , 2003;;Chiquet et al. 2004;Sarasa-Renedo & Chiquet, 2005).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Mackie et al. 1988;Mackie & Tucker, 1999;Järvinen et al. 2000Järvinen et al. , 2003

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted).

    Premisecitation

    The ECM may play a role in the onset of muscle tenderness after a single bout of eccentric exercise.

    “It has previously been hypothesized that the ECM may play a role in the onset of the muscle tenderness after a single bout of eccentric exercise (Stauber et al. 1990;Crameri et al. 2004c;Malm et al. 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Stauber et al. 1990;Crameri et al. 2004c;Malm et al. 2004

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Although acute physiological loading can activate satellite cells, only a marked disruption to the myofibre proteins, leading to inflammatory cell invasion within the myofibre, induced terminal differentiation within the affected myofibre in human skeletal musculature following high-intensity eccentric contractions in the lower limb.

    “Although acute physiological loading can activate satellite cells, only a marked disruption to the myofibre proteins, leading to inflammatory cell invasion within the myofibre, induced terminal differentiation within the affected myofibre in human skeletal musculature following high-intensity eccentric contractions in the lower limb.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data

    In this study, while satellite cells can be activated after a single bout of intense exercise, terminal differentiation seldom occurs without the presence of myofibre necrosis.

    “In this study, we show that while satellite cells can be activated after a single bout of intense exercise, terminal differentiation seldom occurs without the presence of myofibre necrosis.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationreasoning

    It is likely that the non-uniform activation of muscle that occurs with voluntary eccentric contractions protects against cytoskeletal damage, in contrast to electrically stimulated activity, and that this explains the conflicting findings between isolated animal models using electrical stimulation and human studies using voluntary exercise.

    “It is likely that the non-uniform activation of muscle that occurs with voluntary eccentric contractions protects against cytoskeletal damage, in contrast to electrically stimulated activity, and that this explains the conflicting findings between isolated animal models using electrical stimulation and human studies using voluntary exercise.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationown data

    In the lower limbs of humans, muscle contractions derived from an artificial electrical impulse induce disruption of the myofibre proteins and result in terminal satellite cell differentiation following high-intensity eccentric contractions.

    “In conclusion, the present study demonstrates that in the lower limbs of humans, muscle contractions derived from an artificial electrical impulse induce disruption of the myofibre proteins and result in terminal satellite cell differentiation following high-intensity eccentric contractions.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data

    The delayed onset of muscle soreness was not significantly different between the two treatments despite marked differences in intramuscular histological markers, particularly myofibre proteins and satellite cell markers.

    “The present study demonstrates that in human muscle, the delayed onset of muscle soreness was not significantly different between the two treatments despite marked differences in intramuscular histological markers, in particular myofibre proteins and satellite cell markers.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.
50 of 50
  • The paper relies on this without support.

    Baseline histological and molecular characteristics are equivalent between the two legs, even though the baseline biopsy was taken from only one leg.

    “Muscle samples were taken randomly from one leg 48 h prior to the exercise bout (baseline) and from both legs 5, 24, 96 and 192 h after the exercise bout.”
  • The paper relies on this without support.

    Electrical stimulation in this study represents the electrical stimulation used in previous animal studies.

    “electrical muscle stimulation (representing that of previous animal studies)”
  • The paper relies on this without support.

    The difference in myofibre damage between ES and VOL is due to differences in muscle activation pattern rather than the large difference in mechanical force or work between the two modes.

    “Quadriceps knee extension moment of force (peak moment, average moment in total range of motion), power (peak power, mean power) and contractile work during the 210 eccentric loading contractions were substantially greater for the voluntarily activated leg (VOL) than the electrostimulated leg (ES; P < 0.0001; Table 1).”
  • The paper relies on this without support.

    The extracellular matrix transfers up to 70% of the force produced by the myofibre.

    “Since the ECM is known to transfer up to 70% of muscle force produced by the myofibre”
  • The paper relies on this without support.

    The mass distribution, fibre pennation angle and fibre length are about the same for all quadriceps compartments.

    “Given that the mass distribution of 34%, the fibre pennation angle and the fibre length are about the same for all the quadriceps compartments”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Compared with pure maximal voluntary contraction strength, rate of force development is more sensitive to detect acute and chronic changes in neuromuscular function.

    “more sensitive to detect acute and chronic changes in neuromuscular function (see, e.g., Angelozzi et al. 2012; Crameri et al. 2007; Jenkins et al. 2014b; Penailillo et al. 2015)”

    From Rate of force development: physiological and methodological considerations (2016) · cites this paper as Crameri et al. 2007

    The Force data and Discussion report that rapid force characteristics declined more than maximal contraction strength after eccentric exercise, supporting greater sensitivity to acute changes in this setting. The paper does not establish that rate of force development is more sensitive to chronic changes in neuromuscular function. Page numbers were not supplied for these passages. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Discussion incorrectly rules out VOL Z-line damage

    Major

    The discussion says significant Z-line damage was absent in VOL. The electron-microscopy results instead report significant disruption and an increase in fully destroyed Z-lines in that leg.

  • RFD100 suppression is assigned to the wrong follow-up time

    Minor

    The results say RFD100 was suppressed at 96 hours, but Table 2 marks the 192-hour VOL value as significant and does not mark the 96-hour value.

  • Relative-RFD changes cite a time point absent from the table

    Minor

    The results report a VOL relative-RFD reduction at 48 hours, but Table 2 has no 48-hour measurement; its follow-ups are 4, 24, 96 and 192 hours.

  • Discussion places the ES Pax-7 increase at 96 hours

    Minor

    The discussion reports increased ES Pax-7 at 96 hours. The results state that ES Pax-7 was significantly elevated at 192 hours only.

  • Figure 7 caption reverses the VOL desmin finding

    Minor

    The caption claims significant desmin-negative fibres in both legs, while the results explicitly state that none were found in VOL at any measured time. Figure 8's caption also says none were found in VOL.

  • Slow-trial mean-power percentage is incorrect

    Minor

    The ES mean power is 0.14/1.18 × 100 = 11.9% of the VOL value, not 5.9%.

    Reported 5.9 · recomputed 11.864407

  • IMP50 increase is assigned to the wrong follow-up time

    Minor

    The narrative places the ES increase at 96 hours, whereas Table 2 marks only the 192-hour ES value as significant.

  • Discussion calls ES MVC reductions significant despite the reported test

    Minor

    The discussion says both legs had significant MVC reductions at 4 and 24 hours. The results say ES MVC was unchanged apart from a 24-hour decrease, and Table 2 describes even that decrease as nonsignificant (P = 0.06).

  • Discussion overstates when VOL Pax-7 increased

    Minor

    The discussion reports increased VOL Pax-7 at both 96 and 192 hours, while the results say its significant increase occurred only at 96 hours.

  • ES relative-RFD significance is placed at 96 rather than 192 hours

    Minor

    The narrative identifies 96 hours as the exception to unchanged ES relative RFD. In Table 2, both ES relative-RFD rows carry significance marks at 192 hours, not 96 hours.

10 of 10

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Bergstrom J, 1962, Muscle electrolytes in man, Scan J Clin Lab Med, 14, 511

Cited by

Sorted by citations

Authors
Crameri, R. M., Aagaard, P., Qvortrup, K., Langberg, H., Olesen, J., & Kjær, M.
Affiliations
  • Bispebjerg Hospital (DK)
  • University of Southern Denmark (DK)
  • University of Copenhagen (DK)
Corresponding author
Crameri, R. M.
Venue
The Journal of Physiology
Publisher
Wiley
Published
2007-08
Volume
583
Issue
1
Pages
365-380
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
OpenAlex
W1552699877
Cited by
319
References
48
Citations by year
2026: 9 · 2025: 12 · 2024: 14 · 2023: 13 · 2022: 10 · 2021: 20 · 2020: 15 · 2019: 20 · 2018: 17 · 2017: 15 · 2016: 22 · 2015: 13 · 2014: 23 · 2013: 12 · 2012: 24
FWCI
19.96
Type
journal article
Language
en
Open access
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
delayed onset muscle soreness, eccentric exercise, electrical stimulation, voluntary muscle contraction, satellite cells, desmin, myogenin, CD56, Pax7, tenascin-C, extracellular matrix, muscle contraction strength, rate of force development
MeSH terms
Adult, Biopsy, Electric Stimulation, Extracellular Matrix, Humans, Male, Muscle Contraction, Myofibrils, Pain, Vimentin, Biomarkers, Exercise, Muscle, Skeletal, Tenascin, Satellite Cells, Skeletal Muscle

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-02.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-02.

Statistics and arithmetic are recomputed, not judged.

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