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PURPOSE: We aimed to determine whether there are different changes in Achilles tendon (AT) mechanical properties in middle-aged, compared to younger runners that might indicate that tendon fatigue, induced by long-distance running, is age-dependent. METHODS: 27 middle-aged (50-67 years) and 22 younger (21-29 years) participants ran a 21 km route at their own pace (mean and SD: old: 3.1 ± 0.3 m s(-1); young: 3.6 ± 0.5 m s(-1)). We tested for changes in the AT force-elongation relationship using dynamometry and ultrasonography during isometric voluntary ankle plantarflexion ramp contractions, conducted 20-28 h pre-run, immediately pre-run, immediately post-run and 20-28 h post-run. Stride frequency and number were examined to estimate cyclic tensile loading characteristics of the tendon during running. RESULTS: Muscle strength decreased significantly (P

Rule–based strength scaling is an easy, cheap and relatively accurate technique to personalise musculoskeletal models. This paper presents a new strength scaling approach for musculoskeletal models and validates it by maximal voluntary contractions. A heterogeneous group of 63 healthy subjects performed maximal isometric knee extensions. A multiple linear regression analysis resulted in a best–fit rule–based strength scaling equation, with age, mass, height, gender, segment masses and segment lengths as predictors. A second strength scaling equation was obtained through multiple linear regression using backwards elimination, resulting in an equation consisting of only the significant predictors: age, body mass and gender. For validation purposes, 20 newly included healthy subjects performed a maximal isometric leg–press. The newly developed strength scaling technique taking all predictors into account resulted in the most accurate predictions of muscle activities compared to alternative strength scaling methods. These techniques personalise musculoskeletal models to a larger extend. However, some applications that require more detailed personalised models, imaging might be necessary to obtain more specific individual muscle characteristics.

We investigated whether myonuclear number increases in proportion to the increase in fiber size during maturational growth of skeletal muscle. Thoraco-abdominal muscle tissue was obtained from twenty 6-day to 15-year-old boys and girls during cardiothoracic surgery. Cross-sections were stained by anti-laminin for the basal lamina and by DAPI to identify nuclei. Basal lamina was traced on digital images to measure the fiber cross-sectional area (FCSA). Nuclei located within the basal lamina were considered myonuclei if pax7-negative and satellite cell nuclei if pax7-positive. Samples of two children were excluded from analysis because of clear signs of hypoxia as shown by positive carbonic anhydrase IX staining. Linear regression showed that FCSA increased with age by 187 μm(2) ·per annum (R(2) = 0.90; P < 0.001). Satellite cell density showed a dramatic decrease in the first months of life, but this was not accompanied by an increase in myonuclei per muscle fiber cross-section. Till four years of age the number of myonuclei per muscle fiber cross-section remained relatively constant but increased thereafter. Myonuclear domain size showed a steep increase during infancy and reached adult values in the young adolescent phase.

Purpose: To design a time-efficient patient-friendly clinical diffusion tensor MRI protocol and postprocessing tool to study the complex muscle architecture of the human forearm. Materials and Methods: The 15-minute examination was done using a 3 T system and consisted of: T1-weighted imaging, dual echo gradient echo imaging, single-shot spin-echo echo-planar imaging (EPI) diffusion tensor MRI. Postprocessing comprised of signal-to-noise improvement by a Rician noise suppression algorithm, image registration to correct for motion and eddy currents, and correction of susceptibility-induced deformations using magnetic field inhomogeneity maps. Per muscle one to five regions of interest were used for fiber tractography seeding. To validate our approach, the reconstructions of individual muscles from the in vivo scans were compared to photographs of those dissected from a human cadaver forearm. Results: Postprocessing proved essential to allow muscle segmentation based on combined T1-weighted and diffusion tensor data. The protocol can be applied more generally to study human muscle architecture in other parts of the body. Conclusion: The proposed protocol was able to visualize the muscle architecture of the human forearm in great detail and showed excellent agreement with the dissected cadaver muscles. J. Magn. Reson. Imaging 2012;36:237248. (c) 2012 Wiley Periodicals, Inc

The aim of the present study was to evaluate a fast clinical protocol to enable diffusion tensor imaging of the human forearm and assess the reproducibility of six diffusion tensor imaging parameters, i.e., the tensor eigenvalues (λ(1), λ(2), and λ(3)), mean diffusivity, fractional anisotropy, and ellipsoid eccentricity. The right forearms of 10 healthy volunteers were scanned twice, with a 1-week interval. Reproducibility of the diffusion tensor imaging parameters was interpreted using Bland-Altman plots, coefficient of repeatability, repeatability index, and the intraclass correlation coefficient. Analysis was done for three regions of interest: the whole muscle volume, flexor digitorum profundus, and extensor digitorum. The Bland-Altman analysis showed that there is good agreement between the two measurements. Based on the intraclass correlation coefficients, agreement was substantial (0.59 < intraclass correlation coefficient < 0.92) for all six parameters of the whole muscle volume and flexor digitorum profundus but only fair (0.18 < intraclass correlation coefficient < 0.64) for the extensor digitorum. Using a 7 min 40 sec scan protocol, which was well tolerated by the volunteers, the reproducibility of diffusion tensor imaging parameters was demonstrated. However, repeatability varies, depending on the region of interest and diffusion tensor imaging parameters. This should be taken into account when a longitudinal study is designed.

Cellular studies have demonstrated a protective role of mitochondrial hexokinase against oxidative insults. It is unknown whether HK protective effects translate to the in vivo condition. In the present study, we hypothesize that HK affects acute ischemia-reperfusion injury in skeletal muscle of the intact animal. Male and female heterozygote knockout HKII (HK(+/-)), heterozygote overexpressed HKII (HK(tg)), and their wild-type (WT) C57Bl/6 littermates mice were examined. In anesthetized animals, the left gastrocnemius medialis (GM) muscle was connected to a force transducer and continuously stimulated (1-Hz twitches) during 60 min ischemia and 90 min reperfusion. Cell survival (%LDH) was defined by the amount of cytosolic lactate dehydrogenase (LDH) activity still present in the reperfused GM relative to the contralateral (non-ischemic) GM. Mitochondrial HK activity was 72.6 +/- 7.5, 15.7 +/- 1.7, and 8.8 +/- 0.9 mU/mg protein in male mice, and 72.7 +/- 3.7, 11.2 +/- 1.4, and 5.9 +/- 1.1 mU/mg in female mice for HK(tg), WT, and HK(+/-), respectively. Tetanic force recovery amounted to 33 +/- 7% for male and 17 +/- 4% for female mice and was similar for HK(tg), WT, and HK(+/-). However, cell survival was decreased (p = 0.014) in male HK(+/-) (82 +/- 4%LDH) as compared with WT (98 +/- 5%LDH) and HK(tg) (97 +/- 4%LDH). No effects of HKII on cell survival was observed in female mice (92 +/- 2% LDH). In conclusion, in this mild model of acute in vivo ischemia-reperfusion injury, a partial knockout of HKII was associated with increased cell death in male mice. The data suggest for the first time that HKII mediates skeletal muscle ischemia-reperfusion injury in the intact male animal.

Muscle weakness is the main symptom of Pompe disease, a lysosomal storage disorder for which major clinical benefits of enzyme replacement therapy (ERT) have been documented recently. Restoration of skeletal muscle function is a challenging goal. Type 2 muscle fibers of mice with Pompe disease have proven resistant to therapy. To investigate the response in humans, we studied muscle biopsies of a severely affected infant before and after 17 months of therapy. Type 1 and 2a fibers were marked with antibodies, and lysosome-associated membrane protein-1 (Lamp1) was used as the lysosomal membrane marker. Quantitative measurements showed a 2.5-3-fold increase of fiber cross-sectional area of both fiber types during therapy and normalization of the Lamp1 signal in approximately 95% of type 1 and approximately 75% of type 2a fibers. The response of both type 1 and 2a muscle fibers in the patient studied herein corroborates the beneficial effects of enzyme therapy seen in patients with Pompe disease.

Study Design: Diffusion tensor magnetic resonance imaging (DTMRI) reconstruction of lumbar erector spinae (ES) compared with cadaver dissection. Objective: The aim of this study was to reconstruct the human lumbar ES from in vivo DT-MRI measurements and to compare the results with literature and cadaver dissection. Summary of Background Data: DT-MRI enables 3-dimensional in vivo reconstruction of muscle architecture. Insight in ES architecture may improve the understanding of low back function. Furthermore, DT-MRI reconstructions allow individualized biomechanical modeling, which may serve as a clinical tool in injury evaluation and in improvement of understanding of pathologies like scoliosis. Materials and Methods: The lumbar spine of 1 healthy male volunteer was scanned using a 3.0 T clinical MRI scanner. MRI data acquisition consisted of 3 parts: (1) high-resolution T1-weighted turbo spin echo for anatomical reference; (2) DT-MRI measurements for fiber tractography; (3) dual echo gradient echo sequence for signal correction purposes. After processing, DT-MRI data were exported to a custom-built software program for fiber tractography. The resulting reconstructions were anatomically validated by comparison with cadaver dissection and literature. Results: DT-MRI reconstruction of 4 parts of the lumbar ES (thoracic part of iliocostalis lumborum, lumbar part of iliocostalis lumborum, thoracic part of longissimus thoracis, and lumbar part of longissimus thoracis) adequately reflected its complex geometry. Some inaccuracies were found in reconstruction details. DT-MRI reconstructions were generally in agreement with anatomical descriptions from literature and with findings in a dissected cadaver specimen. Conclusions: DT-MRI enables anatomically valid reconstruction of ES architecture. However, for reliable reconstruction of the smallest fascicles and attachments a higher resolution or application of higher-order models is needed. Reconstructions can be used as input for estimation of muscle architecture parameters in individualized biomechanical modeling. Such models are promising as a tool in clinical evaluation and in research of low back pain mechanisms.

PURPOSE: To prospectively evaluate quantitative diffusion magnetic resonance (MR) imaging for monitoring skeletal muscle injury and repair after femoral artery ligation in mice. MATERIALS AND METHODS: All experimental procedures were approved by the local institutional animal care and use committee. Muscle degeneration and regeneration were induced in 16 mice by using unilateral ligation of the femoral artery. Diffusion-tensor and T2-weighted MR imaging examinations were performed before, immediately after, and 3, 10, and 21 days after ligation. Histologic analysis was also performed at these time points. The dynamic changes in T2 and in five diffusion-tensor imaging indexes were studied by using histogram analysis. Differences between the ligated and nonligated limbs were assessed with paired t tests, and analysis of variance was used to determine temporal evolutions. Parametric maps were clustered to depict regional differences in the responses of the different MR imaging indexes. RESULTS: MR indexes in the ligated limb changed over time (P < .007), and temporal evolutions in the ligated and nonligated limbs differed significantly (P < .001). When ischemia was induced, diffusivity and T2 increased, with a maximum change at 3 days, when most muscle damage was observed at histologic analysis. At 10 days, diffusion values were reduced overall, whereas T2 was still increased. At 21 days, parameter values had largely returned to normal. Changes on the diffusion-tensor and T2 maps had spatial differences, which corresponded to the different phases of tissue regeneration observed at histologic analysis. An additional finding was the transient change in direction of the principal eigenvector during the period of maximal muscle damage. CONCLUSION: After femoral artery ligation, the diffusion-tensor indexes changed dynamically in association with the severity and location of muscle damage.

We investigated the temporal effects of sepsis on muscle wasting and function in order to study the contribution of wasting to the decline in muscle function; we also studied the fiber-type specificity of this muscle wasting. Sepsis was induced by injecting rats intraperitoneally with a zymosan suspension. At 2 h and at 2, 6, and 11 days after injection, muscle function was measured using in situ electrical stimulation. Zymosan injection induced severe muscle wasting compared to pair-fed and ad libitum fed controls. At 6 days, isometric force-generating capacity was drastically reduced in zymosan-treated rats. We conclude that this was fully accounted for by the reduction of muscle mass. At day 6, we also observed increased activity of the 20S proteasome in gastrocnemius but not soleus muscle from septic rats. In tibialis anterior but not in soleus, muscle wasting occurred in a fiber-type specific fashion, i.e., the reduction in cross-sectional area was significantly smaller in type 1 than type 2A and 2B/X fibers. These findings suggest that both the inherent function of a muscle and the muscle fiber-type distribution affect the responsiveness to catabolic signals. Muscle Nerve, 2005.

A hallmark of glycogen storage disease type II, caused by defective alpha-glucosidase (AGLU) activity, is a progressive decline in muscle performance. The objective of this study was to determine the relative contribution to this decline in muscle performance of (1) decline in muscle mass; (2) decline in muscle protein content per unit mass; and (3) accumulation of glycogen. To this end, isometric torque and power in AGLU(-/-) mice at 7, 13, and 20 months were assessed in situ. Power (approximately 24 mW) and torque (approximately 2.45 Nmm) did not change with age in control animals, but declined significantly in AGLU(-/-) mice, in the three age groups. No decline in protein content per unit muscle mass was observed. Muscle atrophy explained one third of the decline in muscle performance; the remaining part was attributed to a decrease in muscle quality--a decrease in mechanical performance per unit muscle mass. Mechanical effects of glycogen inclusions could not fully explain this decrease. Additional factors must therefore play a role.

A modified PAS stain combined with immunofluorescence for quantitative analyses of glycogen in muscle sections.Schaart G, Hesselink RP, Keizer HA, van Kranenburg G, Drost MR, Hesselink MK.Department of Movement Sciences, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.Simultaneous analyses of glycogen in sections with other subcellular constituents within the same section will provide detailed information on glycogen deposition and the processes involved. To date, staining protocols for quantitative glycogen analyses together with immunofluorescence in the same section are lacking. We aimed to: (1) optimise PAS staining for combination with immunofluorescence, (2) perform quantitative glycogen analyses in tissue sections, (3) evaluate the effect of section thickness on PAS-derived data and (4) examine if semiquantitative glycogen data were convertible to genuine glycogen values. Conventional PAS was successfully modified for combined use with immunofluorescence. Transmitted light microscopic examination of glycogen was successfully followed by semiquantification of glycogen using microdensitometry. Semiquantitative data correlated perfectly with glycogen content measured biochemically in the same sample (r2=0.993, P

MR offers powerful tools to measure molecular diffusion in intact tissues under in vivo conditions. This review focuses on the use of diffusion-weighted MR imaging (DW-MRI) and spectroscopy (DW-MRS) to noninvasively study structural and functional aspects of skeletal muscle. It will be shown that DW-MRI allows for a high-resolution reconstruction of the orientation of the muscle fibers, which represents vital input for mathematical models of muscle biomechanics and an improved understanding of contractile dysfunction in muscle disease. DW-MRS can be used to quantitatively measure the translational displacement of endogenous metabolites in intact muscle. DW-MRS is of fundamental interest because it enables one to probe the in situ status of the intracellular space from the diffusion characteristics of the metabolites, while at the same time providing information on the intrinsic diffusion properties of the metabolites themselves. This yields information on cellular architecture and on the intrinsic capacity for diffusional mass transport.

The aim of this study was to determine the relationship between ankle dorsiflexor strength and performances on several walking tests and to determine the effect of ankle-foot orthosis (AFO) use on walking tests. The following tests were used: 10-metre walking test (with and without three stairs), a complex walking task (6-minute walk with cognitive loading) and a subjective evaluation (SIP68 mobility scale and questionnaire). Isometric strength of the ankle dorsiflexors was measured. All walking tests were performed with and without AFO in random order. When relating torque values to walking performances, the highest correlation was found with the "10 metre" and "10 metre with stairs" test (r = -0.51, i.e. an inverse relationship). No threshold in the degree of paresis was found below which walking disability suddenly increased. No significant improvement could be demonstrated from AFO use on the 10-metre tests. Improvement on the 6-minute test was nearly significant (p = 0.06), the questionnaire revealed a positive opinion on AFO use related to overall walking function and effort. Thus, we have to conclude that these walking tests do not aid the clinician in estimating the severity of (progression of) the paresis nor to detect differences in degree of paresis between subjects.

Department of Physiology, University of Maastricht, 6200 MD Maastricht, The Netherlands.GLUT-4 plays a predominant role in glucose uptake during muscle contraction. In the present study, we have investigated in mice whether disruption of the GLUT-4 gene affects isometric and shortening contractile performance of the dorsal flexor muscle complex in situ. Moreover, we have explored the hypothesis that lack of GLUT-4 enhances muscle fatigability. Isometric performance normalized to muscle mass during a single tetanic contraction did not differ between wild-type (WT) and GLUT-4-deficient [GLUT-4(-/-)] mice. Shortening contractions, however, revealed a significant 1.4-fold decrease in peak power per unit mass, most likely caused by the fiber-type transition from fast-glycolytic fibers (IIB) to fast-oxidative fibers (IIA) in GLUT-4(-/-) dorsal flexors. In addition, the resting glycogen content was significantly lower (34%) in the dorsal flexor complex of GLUT-4(-/-) mice than in WT mice. Moreover, the muscle complex of GLUT-4(-/-) mice showed enhanced susceptibility to fatigue, which may be related to the decline in the muscle carbohydrate store. The significant decrease in relative work output during the steady-state phase of the fatigue protocol suggests that energy supply via alternative routes is not capable to compensate fully for the lack of GLUT-4.

Janssen-Potten YJ, Seelen HA, Drukker J, Spaans F, Drost MR. The effect of footrests on sitting balance in paraplegic subjects. Arch Phys Med Rehabil 2002;83:642-8. Objective: To test the hypothesis that footrests contribute to active control of sitting balance. Design: Cross-sectional group study. Setting: Rehabilitation center. Participants: Ten persons with complete low thoracic (T9-12) spinal cord injury (SCI), 10 persons with complete lumbar (L1-5) SCI, and 10 matched able-bodied controls. Intervention: An elastically suspended footrest. Main Outcome Measures: Reaching distance, time needed to perform a bimanual forward-reaching movement, center of pressure displacement, and muscle activity. Results: Controls performed the forward-reaching movement slower and with less forward acceleration of the center of mass (COM) in the chair with the elastic footrest. Furthermore, they revealed a typical change in muscle activity patterns when the solid footrest was replaced by the elastic one. Persons with SCI performed the forward-reaching movement equally fast in both footrest conditions, but those with lumbar SCI showed less forward acceleration of the COM, whereas persons with thoracic SCI revealed more forward acceleration of the COM in the chair with the elastic footrest. Muscle activity patterns in persons with SCI did not indicate alternative muscle use through possible compensations or reflex activity. Conclusions: Regarding wheelchair design, footrest condition does not seem to affect the range in which manual activities of daily living can be performed, but it does affect how they are performed. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Neuromuscular Research Center, Department of Biology of Physical Activity, University of Jyvaskyla, PO Box 35, 40351, Finland. koskinen@maila.jyu.fiAcute downhill running has been shown to activate matrix metalloproteinase- (MMP-) 2 and to change type IV collagen concentration in some muscle types. In order to study the influence of more intense exercise on total collagen and type IV collagen concentrations, molecules regulating their synthesis and degradation were investigated after forced lengthening contractions in rat skeletal muscle. Tibialis anterior (TA) muscle of 24 male Wistar rats was subjected to 240 forced lengthening contractions. TA muscle was excised at consecutive time points (0 and 6 h, 2, 4, and 7 days) after stimulation. With immunohistochemistry, types I, III and IV collagen were located in the swollen, necrotic and regenerated fibres in a similar manner as in intact undamaged skeletal muscle fibre. An increase in the activity of prolyl 4-hydroxylase was indicative of an overall elevated collagen biosynthesis. No change was demonstrated in total collagen concentration, whereas type IV collagen concentration increased after exercise. MMP-2 and MMP-9, which are the proteins that degrade type IV collagen, elevated after exercise. In conclusion, the increase in type IV collagen concentration seems to be the result of an increase in both the synthesis and activation of degrading enzymes and their inhibitors during recovery after forced lengthening contractions.

Institute for Rehabilitation Research, Hoensbroek & Atrium Medical Centre, Heerlen, The Netherlands. m.geboers@zonnet.nlOBJECTIVES: To determine (1) whether use of an ankle-foot orthosis (AFO) by patients with ankle dorsiflexor paresis leads to decreased muscle activity, immediately or 6 weeks after AFO use, and (2) whether this decrease (if present) differs between healthy and paretic subjects. DESIGN: Cross-sectional and longitudinal randomized case-control study. SETTING: Rehabilitation research center in the Netherlands. PARTICIPANTS: Fourteen healthy persons and 29 patients with foot drop. INTERVENTIONS: Muscle activity was measured by surface electromyography. Electromyographic reproducibility was tested in 14 healthy volunteers walking with and without AFO. Acute changes in muscle activity from AFO use were compared between the 14 healthy persons and the 29 patients with foot drop. Adaptation effects of AFO use after 6 weeks were studied in 29 patients, randomly chosen 16 of whom had started using an AFO at the first measurement. MAIN OUTCOME MEASURES: Amount of change in mean rectified electromyographic activity (delta value) between walking with and without AFO. Follow-up measurements were conducted after 3 and 6 weeks. RESULTS: Correlation coefficients, reflecting within-subject reproducibility, varied between.68 and.96 (mean,.86). In patients and healthy subjects, tibialis anterior muscle activity decreased by 7% and 20% (P = .01, P = .04), respectively, when using an AFO. In patients, this decrease was measured in the overall activity during the gait cycle; in healthy subjects, it was measured in the first 15% of the gait cycle. Overall electromyographic activity did not change during 6 weeks; delta values per muscle did not change during follow-up in the AFO group. CONCLUSION: AFO use immediately reduced muscle activity of the ankle dorsiflexors. However, using an AFO for 6 weeks did not lead to a generally lower electromyographic activity level nor did the amount of activity reduction accumulate in comparison with patients who did not use an AFO. It is, therefore, safe to use an AFO, even with recently paretic patients. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and RehabilitationPublication Types: Clinical Trial Randomized Controlled Trial

Arch Phys Med Rehabil 2001 Jun;82(6):856-60 Related Articles, Books, LinkOut Evaluation of effect of ankle-foot orthosis use on strength restoration of paretic dorsiflexors.Geboers JF, Janssen-Potten YJ, Seelen HA, Spaans F, Drost MR.Institute for Rehabilitation Research, Hoensbroek, the Netherlands. marion.geboers@irv.nlOBJECTIVE: To assess whether a difference exists in restoration of strength between patients with a recent paresis of the dorsiflexors of the ankle using an ankle-foot orthosis (AFO) and patients without an AFO. DESIGN: Prospective case-control study. SETTING: Patients from regional hospitals, tested in a rehabilitation research center. PARTICIPANTS: Twenty-nine patients with a recent (6wk-1yr) peripheral paresis, alternately assigned to a group using an AFO or a control group. There was no significant difference in duration of the paresis and in torque at entering the study (T0) between the 2 groups. INTERVENTIONS: The use of an ankle-foot orthosis. MAIN OUTCOME MEASURES: Isometric torque production of ankle dorsiflexors, expressed as ratio of paretic and healthy side, in 2 measurement sessions, over a period of 6 weeks (T0-T6) with the ankle in 0 degrees and 30 degrees plantarflexion. RESULTS: Both groups had significant restoration of strength +/- standard deviation between T0 and T6 in 30 degrees flexion: non-AFO group 17% +/- 15%, AFO group 9% +/- 12%. No significant difference existed between the 2 groups (30 degrees p = .56). No significant shift in strength ratio 0 degrees :30 degrees occurred (AFO group p = .82). CONCLUSION: The use of an orthosis does not influence restoration of strength in patients with a recent peripheral paresis of the ankle dorsiflexors.

J Biomech 2001 May;34(5):631-7 Related Articles, Books, LinkOut Spatial interaction between tissue pressure and skeletal muscle perfusion during contraction.van Donkelaar CC, Huyghe JM, Vankan WJ, Drost MR.Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB, Eindhoven, Netherlands. c.c.v.donkelaar@tue.nlThe vascular waterfall theory attributes decreased muscle perfusion during contraction to increased intramuscular pressure (P(IM)) and concomitant increase in venous resistance. Although P(IM) is distributed during contractions, this theory does not account for heterogeneity. This study hypothesises that pressure heterogeneity could affect the interaction between P(IM) rise and perfusion. Regional tissue perfusion during submaximum (100kPa) tetanic contraction is studied, using a finite element model of perfused contracting skeletal muscle. Capillary flow in muscles with one proximal artery and vein (SIM(1)) and with an additional distal artery and vein (SIM(2)) is compared. Blood flow and pressures at rest and P(IM) during contraction ( approximately 25kPa maximally) are similar between simulations, but capillary flow and venous pressure differ. In SIM(2), venous pressure and capillary flow correspond to P(IM) distribution, whereas capillary flow in SIM(1) is less than 10% of flow in SIM(2), in the muscle half without draining vein. This difference is caused by a high central P(IM), followed by central venous pressure rise, in agreement with the waterfall theory. The high central pressure (SIM(1)), obstructs outflow from the distal veins. Distal venous pressure rises until central blood pressure is reached, although local P(IM) is low. Adding a distal vein (SIM(2)) restores the perfusion. It is concluded that regional effects contribute to the interaction between P(IM) and perfusion during contraction. Unlike stated by the vascular waterfall theory, venous pressure may locally exceed P(IM). Although this can be explained by the principles of this theory, the theory does not include this phenomenon as such.

Arch Phys Med Rehabil 2001 Oct;82(10):1393-402 Related Articles, Books, LinkOut The effect of seat tilting on pelvic position, balance control, and compensatory postural muscle use in paraplegic subjects.Janssen-Potten YJ, Seelen HA, Drukker J, Huson T, Drost MR.Institute for Rehabilitation Research, Hoensbroek, The Netherlands. Yvonne.Potten@iRv.nlOBJECTIVE: To study the effect of seat tilting on pelvic tilt, balance control, and postural muscle use in persons with a thoracic spinal cord injury (SCI). DESIGN: Cross-sectional group study. SETTING: Rehabilitation centers and rehabilitation hospital departments. PATIENTS: Ten complete high thoracic SCI (level T2-8) patients, 10 complete low thoracic SCI (level T9-12) patients, and 10 matched able-bodied controls. INTERVENTION: A 10 degrees forward inclination of the seat. MAIN OUTCOME MEASURES: Pelvic tilt, center of pressure displacement, and muscle activity. RESULTS: Anterior tilting of the pelvis as a result of forward inclination of the seat could not be shown, either in persons with or without SCI. Balance control was not influenced by forward inclination of the seat. Participants' overall muscle activity decreased while they were seated in the chair with the forwardly inclined seat. CONCLUSIONS: Evidence provided by the kinematic and electromyographic data is not sufficient to develop a protocol for wheelchair prescription on the basis of pelvic positioning. Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Murine muscles lacking both mitochondrial (Mi-CK) and cytoplasmic (MM-CK) creatine kinase (CK-/-) show depressed mechanical performance in association with low muscle ATP and enhanced IMP content. The aims of the present study were to elucidate the possible role of low ATP and high IMP content in impairment of mechanical performance in CK-/- mice and to establish whether CK-/- muscles are able to sustain repeated series of high-intensity contractions. The dorsal flexors of CK-/- and control mice were subjected in situ to two series of 12 tetanic contractions using a custom-made mouse isometric dynamometer. The muscle content of high-energy phosphates was analysed by HPLC. ATP content declined from 20.6 +/-1.9 to 15.5 +/-2.4 mu mol g(-1) dry weight (d.w.); IMP content increased from 1.2 +/-0.4 to 2.4 +/-1.1 mu mol g(-1) d.w. during the first contraction series in CK-/- muscle. Despite these unfavourable changes, maximal torque developed during the first contraction of either series did not differ, indicating that the altered content of ATP and IMP does not play a decisive role in impaired mechanical performance in CK-/- mice. The relative decline in torque during the two series did not differ in CK-/- (-20.4 +/-6.6 vs. -23.8 +/-9.9%). In contrast. wild-type (WT) muscles showed a significantly more pronounced decline during the second series (-12.3 +/-7.4 vs. -20.1 +/-6.8%). Muscle ATP and IMP content did not change in CK-/-, whereas in WT IMP content increased significantly during the second contraction series. These findings indicate that CK-/- tolerate repeated series of high-intensity contractions better than WT, while in CK-/- muscle an additional source of energy is mobilised to regenerate ATP during the second series.

Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis, The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition. Vegf(165) promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons.

Am J Physiol Endocrinol Metab 2001 Sep;281(3):E619-25 Related Articles, Books, LinkOut Impaired muscular contractile performance and adenine nucleotide handling in creatine kinase-deficient mice.Gorselink M, Drost MR, Coumans WA, van Kranenburg GP, Hesselink RP, van der Vusse GJ.Department of Physiology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.Creatine kinase (CK) forms a small family of isoenzymes playing an important role in maintaining the concentration of ATP and ADP in muscle cells. To delineate the impact of a lack of CK activity, we studied contractile performance during a single maximal tetanic contraction and during 12 repeated tetanic contractions of intact dorsal flexors of CK knockout (CK(-/-)) mice. To investigate the effect on ATP regeneration, muscular high-energy phosphate content was determined at rest, immediately after the contraction series, and after a 60-s recovery period. Maximal torque of the dorsal flexors was significantly lower in CK(-/-) mice than in wild-type animals, i.e., 23.7 +/- 5.1 and 33.3 +/- 6.8 mN. m. g(-1) wet wt, respectively. Lower muscle ATP (20.1 +/- 1.4 in CK(-/-) vs. 28.0 +/- 2.1 micromol/g dry wt in controls) and higher IMP (1.2 +/- 0.5 in CK(-/-) vs. 0.3 +/- 0.1 micromol/g dry wt in controls) levels at the onset of contraction may contribute to the declined contractility in CK(-/-) mice. In contrast to wild-type muscles, ATP levels could not be maintained during the series of 12 tetanic contractions of dorsal flexors of CK(-/-) mice and dropped to 15.5 +/- 2.4 micromol/g dry wt. The significant increase in tissue IMP (2.4 +/- 1.1 micromol/g dry wt) content after the contraction series indicates that ATP regeneration through adenylate kinase was not capable of fully compensating for the lack of CK. ATP regeneration via the adenylate kinase pathway is a likely cause of reduced basal adenine nucleotide levels in CK(-/-) mice.

In the present paper the effect of repeated lengthening exercise on the expression of cytoskeletal proteins was studied in rat skeletal muscle. Tibialis anterior muscles were subjected to an exercise session consisting of 240 lengthening (L) or shortening (S) contractions. Muscles were excised 4 days post-exercise. Contralateral muscles served as controls (C). Western blotting was done with antibodies against desmin and vimentin. In C and S immunostaining yielded a regular cross-striated pattern, in L however, fibers can be detected without immunostaining. Western blots showed no major differences in the amount of desmin between C, S and L, although some proteolysis was present in L. Vimentin was absent in C and S, and prominently present in L. These data indicate that remodeling of the intermediate filament lattice after damage induced by lengthening exercise occurs in a differentiation like manner.

To compensate for postural muscle function loss spinal cord injured (SCI) people have to use parts of the sensorimotor system which are still intact. In this study, postural control was investigated in high and low thoracic SCI people and in able-bodied controls, using a bimanual forward-reaching task. Muscle activity was recorded bilaterally from the erector spinae (ES) at level L3, T9 and T3, latissimus dorsi (LD), ascending part of the trapezius muscle (TPA), serratus anterior (SA), sternocostal head of the pectoralis major (PM) and the oblique abdominal muscles (OA) by means of surface electromyography. Sitting balance was monitored by measuring the changes in the location of the centre of pressure (CP) using a force platform. Muscle activity analyzed in different phases of the movement showed that SCI people adopt different postural adjustments to face the balance changes due to the reaching movement. SCI people make alternative use of non-postural muscles like the LD and TPA to maintain their sitting balance.

An important assumption in 2D numerical models of skeletal muscle contraction involves deformation in the third dimension of the included muscle section. The present paper studies the often used plane strain description. Therefore, 3D muscle surface deformation is measured from marker displacements during isometric contractions at various muscle lengths. Longitudinal strains at superficial muscle fibers( - 14 +/- 2.6% at L-0, n = 57) and aponeurosis (0.8 +/- 0.9% at L-0) decrease with increasing muscle length. The same holds for transverse muscle surface strains in superficial muscle fibers and aponeurosis, which are comparable at intermediate muscle length, but differ at long and short muscle length. Because transverse strains during isometric contraction change with initial muscle length, it is concluded that the effect of muscle length on muscle deformation cannot be studied in plane strain models. These results do not counteract the use of these models to study deformation in contractions with approximately - 9% longitudinal muscle fiber strain, as transverse strain in superficial muscle fibers and in aponeurosis tissue is minimal in that case. Aponeurosis surface area change decreases with increasing initial muscle length, but muscle fiber surface area change is - 11%, independent of muscle length. Assuming incompressible muscle material, this means that strain perpendicular to the muscle surface equals 11%. Taking the relationship between transverse and longitudinal muscle fiber strain into account, ii is hypothesized that superficial muscle fibers flatten during isometric contractions. (C) 1999 Elsevier Science Ltd. All rights reserved

Optical marker tracing methods have been applied successfully in recent years to quantify local material deformation of heart tissue, skin and striated muscles. In this study, polystyrene fluorescent spheres (d = 0.6 mm) are glued to the ventral serosal bladder wall in the rabbit. Three dimensional video registration of the polystyrene spheres is used to calculate two directions of principal strain (epsilon (1), epsilon (2) ) on the bladder surface in vivo. The aim is to investigate the feasibility of the technique for this new application in two experimental circumstances: during spontaneous bladder wall activity and after electrical stimulation of bladder innervating nerve fibers. During spontaneous activity, random contraction and relaxation occurred simultaneously and separately across the bladder wall for the two principal strains epsilon (1) and epsilon (2). After extradural electrical stimulation of sacral nerve root S2, the principal strains epsilon ( 1) and epsilon (2) synchronized in time in such a way that epsilon ( 1) and epsilon (2) both represented contraction or both represented relaxation. One and the same bladder wall area passed through phases of contraction followed by relaxation and vice versa. After multiple stimulation periods, the coordination between the two principal strains during stimulation was reduced. This technique allows to identify local areas of contraction and relaxation in the intact bladder wall in vivo. Three dimensional video registration of polystyrene fluorescent spheres to study bladder wall contraction and its relaxation proved to be a feasible technique, with which electrical stimulation effects and spontaneous activity could be measured.

In numerical simulations of skeletal muscle contractions, geometric information is of major importance. The aim of the present study was to determine whether the diffusion tensor imaging (DTI) technique is suitable to obtain valid input with regard to skeletal muscle fibre direction. The accuracy of the DTI method was therefore studied by comparison of DTI fibre directions in the rat tibialis anterior muscle with fascicle striation patterns visible on high-resolution magnetic resonance imaging (MRI) and with fibre directions in an actual longitudinal section (ALS) through the same muscle. The results showed an excellent qualitative agreement between high-resolution MRI and DTI. Despite less accurate quantitative comparison with ALS, it was concluded that DTI does indeed measure skeletal muscle fibre direction. After the experiment, it was possible to determine an appropriate voxel size (0.9 mm3) that provided enough resolution and acceptable accuracy (5 degrees) to use DTI fibre directions in biomechanical analyses. Muscle deformation during contraction, resulting from a finite element simulation with a mesh that was directly generated from the experimental data, has been presented.

A finite element (FE) model of blood perfused biological tissue has been developed. Blood perfusion is described by fluid flow through a series of 5 intercommunicating vascular compartments that are embedded in the tissue. Each compartment is characterized by a blood flow permeability tensor, blood volume fraction and vessel compliance. Local non-linear relationships between intra-extravascular pressure difference and blood volume fraction, and between blood volume fraction and the permeability tensor, are includedin the FE model. To test the implementation of these non-linear relations, FE results of blood perfusion in a piece of tissue that is subject to increased intramuscular pressure, are compared to results that are calculated with a lumped parameter (LP) model of blood perfusion. FE simulation of blood flow through a contracting rat calf muscle is performed. The FE model used in this simulation contains a transversely isotropic, non-linearly elastic description of deforming muscle tissue, in which local contraction stress is prescribed as a function of time. FE results of muscle tension, total arterial inflow and total venous outflow of the muscle during contraction, correspond to experimental results of an isometrically and tetanically contracting rat calf muscle.

An in vivo method for measuring local deformations of the surface of skeletal muscles is presented. The method was applied to the aponeurosis of the medial gastrocnemius muscle (MG) of cat. Approximately 150 fluorescent polystyrene markers were attached to the aponeurosis and the distal muscle fibres of the MG. Two-dimensional video recordings of the muscle-tendon complex in situ during active force production at fixed muscle length were made. Principal strains (ε1 and ε2) and strains in the longitudinal direction of the muscle-tendon complex (εlon) and in the transverse direction (εt) were calculated. The aponeurosis extended during contraction of the MG. Mean longitudinal strain of the aponeurosis was approximately 2%. An increase in strain was found in the disto-proximal direction. In the transverse direction, large inhomogeneities in the strain were found.

Previous studies have shown that lengthening contractions, in contrast to isometric contractions, readily result in sustained malfunctioning of the exercised muscles. The present study was performed to investigate whether an exercise period with many (240) lengthening contractions (LC) results in alterations in muscle high-energy phosphates and inosine monophosphate (IMP) content, different from muscles performing a few (60) lengthening or a few (60) or many (240) isometric contractions (IC). Moreover, we sought for a possible cause(s) of the inability to replenish muscle glycogen stores following LC. Rat tibialis anterior muscles were subjected in vivo to either 60 or 240LC or IC. Structural muscle damage occurred only after 240LC. The fact that tissue glycogen levels declined to a similar extent during LC and IC suggests that the energy demand was comparable during both types of exercise. Nevertheless, the observation that on the one hand tissue stores of adenine nucleotides showed a greater decline, and on the other hand the tissue content of IMP increased to a significantly higher level after LC than after IC, clearly indicates that muscle energy metabolism is more disturbed during LC than during IC. The high tissue levels of IMP may contribute to impaired mechanical function as previously observed in muscles subjected to LC. In contrast to 240IC, 24 hours after 240LC, tissue glycogen stores and high-energy phosphate levels were not restored to control values. The present findings indicate that depressed glycogen synthase activity and impaired activity of the mitochondrial marker enzyme cytochrome C oxidase probably contribute to a continuous disturbance of energy metabolism in the exercised muscles during the 24 hours following 240 LC.

Changes in satellite cell content play a key role in regulating skeletal muscle growth and atrophy. Yet, there is little information on changes in satellite cell content from birth to old age in humans. The present study defines muscle fiber type-specific satellite cell content in human skeletal muscle tissue over the entire lifespan. Muscle biopsies were collected in 165 subjects, from different muscles of children undergoing surgery ( < 18 years; n = 13 ) and from the vastus lateralis muscle of young adult ( 18–49 years; n = 50 ), older ( 50–69 years; n = 53 ), and senescent subjects ( 70–86 years; n = 49 ). In a subgroup of 51 aged subjects ( 71 ± 6 years ), additional biopsies were collected after 12 weeks of supervised resistance-type exercise training. Immunohistochemistry was applied to assess skeletal muscle fiber type-specific composition, size, and satellite cell content. From birth to adulthood, muscle fiber size increased tremendously with no major changes in muscle fiber satellite cell content, and no differences between type I and II muscle fibers. In contrast to type I muscle fibers, type II muscle fiber size was substantially smaller with increasing age in adults ( r = −0.56; P < 0.001 ). This was accompanied by an age-related reduction in type II muscle fiber satellite cell content ( r = −0.57; P < 0.001 ). Twelve weeks of resistance-type exercise training significantly increased type II muscle fiber size and satellite cell content. We conclude that type II muscle fiber atrophy with aging is accompanied by a specific decline in type II muscle fiber satellite cell content. Resistance-type exercise training represents an effective strategy to increase satellite cell content and reverse type II muscle fiber atrophy.

Mechanical interaction between tissue stress and blood perfusion in skeletal muscles plays an important role in blood flow impediment during sustained contraction. The exact mechanism of this interaction is not clear, and experimental investigation of this mechanism is difficult. We developed a finite-element model of the mechanical behavior of blood-perfused muscle tissue, which accounts for mechanical blood-tissue interaction in maximally vasodilated vasculature. Verification of the model was performed by comparing finite-element results of blood pressure and flow with experimental measurements in a muscle that is subject to well-controlled mechanical loading conditions. In addition, we performed simulations of blood perfusion during tetanic, isometric contraction and maximal vasodilation in a simplified, two-dimensional finite-element model of a rat calf muscle. A vascular waterfall in the venous compartment was identified as the main cause for blood flow impediment both in the experiment and in the finite-element simulations. The validated finite-element model offers possibilities for detailed analysis of blood perfusion in three-dimensional muscle models under complicated loading conditions.

SUMMARY A nite element description of uid ow through a deforming porous solid, with a hierarchical structure of pores, has been developed and implemented in the nite element software package DIANA. 1 Several standard element types can be used for 2-D, axisymmetric and 3-D nite deformation analysis. The hierarchy is dealt with as an extra dimension, quantied by a parameter x0. Both spatial and hierarchical uid ow is described by a Darcy equation. Fluid pressure and hydrostatic solid pressure are related via an elastic uid{solid interface. The state of the uid, the Darcy permeability tensor and the elastic interface depend on both spatial position and hierarchical level. Discretization and integration of uid related quantities are split into a spatial and a hierarchical part. The degrees of freedom of the nite element model are the displacements of the solid, the hydrostatic pressure and a number of uid pressures on dierent hierarchical levels. Blood-perfused biological tissue can be regarded as a hierarchical porous solid, where the uid represents the blood and the hierarchy corresponds to the tree-like vascular structure. As an example, a simulation of a contracting, blood-perfused skeletal muscle is presented. Blood perfusion is a complex and sophisticated mechanism of nutrition and drainage of biological tissues. Some of these tissues are subject to large mechanical loads and deformations. Mechanical processes in the tissue can signicantly interact with blood perfusion. 2;3 In order to investigate these mechanical processes and interactions, the material behaviour of the tissue can be mathematically modelled by means of the mixture theory. 4;5 Blood-perfused biological tissue can be described as a mixture, in which the uid phase represents the blood and the surrounding tissue is represented by the solid. The blood vessels can be regarded as pores in the solid. An essential aspect of vasculature is its hierarchical architecture: the blood ows from one or a few large supplying arteries through a diverging, arteriolar vascular bed (Figure 1), reaches the capillaries, and is drained by a converging venous vasculature. In the greater part of the hierarchy, vessels are numerous and lie homogeneously distributed in the tissue. Within each small and bounded spatial region in the tissue (averaging volume in mixture theory), we therefore distinguish between blood that resides in the dierent parts of the hierarchy. Vascular properties, like vessel diameter, wall thickness and stiness, vessel orientation and vessel

Study Design. This report examines the permeability coefficient and aggregate modulus of slices of anuius cut from canine lumbar intervertebral discs. Objectives. To examine the influence of radial position on the properties of these materials, including outer samples with intact anuius edge. Summary of Background Data. The outer edge of anulus fibrosus shows radial bulge during axial compression of motion segments. The radial bulge increases monotonically when the axial compression is sustained for several hours, until a plateau is reached. Triphasic modeling of axial compression shows that this time course of radial bulge can not be obtained using a uniform permeability coefficient according to values in the literature. Methods. Confined consolidation experiments (controlled load) were designed to measure the time course of uniaxial deformation of samples of anulus that were 4 mm in diameter and 1 mm tall. The rotation symmetry axis of the samples was defined in the radial direction of the disc. The radial permeability coefficient and the aggregate modulus were determined using the consolidation data and the linear biphasic theory. Results. The permeability coefficient was lower at the periphery than in deeper layers of the anulus. Outer samples with outer surfaces that were 0.0-0.5 mm from the anulus edge had an average permeability coefficient of (1.02 ± 0.57) x 10 -16 m 4 /Ns (n = 24). Inner samples that were 2.0-2.5 mm from the anulus edge had an average permeability coefficient of (2.81 ± 0.98) x 10 -16 m 4 /Ns (n = 13). The aggregate modulus H A of outer samples was significantly higher (H A 1.56 ± 0.34 MPa) than that of inner samples (H A = 1.31 ± 0.47 MPa). Conclusions. The fact that the outer anuius is less permeable than the inner anuius may explain why radial bulge of anulus fibrosus increases monotonically in time to an equilibrium value during sustained axial compression of a motion segment.

Biomechanical studies have shown that the distribution of stress and strain in biological tissue is strongly dependent on fibre orientation. Therefore, to analyze the local mechanical load, accurate data on muscle fibre orientation are needed. Traditional techniques to determine fibre orientation are inherently invasive. Here we used Diffusion Weighted MRI to non-invasively determine, in each image voxel of 0.23 x 0.23 mm, the diffusion tensor of water in the cat semimembranosus muscle. The direction corresponding to the largest eigenvector of this tensor was calculated. This direction was found to correspond qualitatively to the muscular fibre direction, as determined by visual inspection.

In order to simulate blood flow in skeletal muscle, our group has developed a finite element description of perfused skeletal muscle. This model requires input parameters concerning the vascular system, muscle contraction and the geometry of a muscle, including its aponeuroses. The objective of the present paper is to create a geometrical reconstruction of the rat gastrocnemius medialis muscle that can be incorporated in the finite element model. Since this muscle is connected to the plantaris and the gastrocnemius lateralis muscle, a detailed computer graphical reconstruction of the triceps surae muscle, based on histological cross-sections, has been accomplished first. Using this reconstruction, relevant sections were selected to create the finite element mesh of the gastrocnemius me! dialis muscle. Special attention was payed to the location of the aponeuroses. The mesh can be used in finite element simulations of perfused skeletal muscle.

Deformation of the surface of passive medial gastrocnemius muscle (MG) was measured in vivo while performing a hysteresis test. The gastrocnemius muscle of male rats were dissected free and the distal tendon was cut. The lateral head was separated from the medial head. The muscle origins were left intact. 60-70 fluorescent, polystyrene spheres (diameter 0.7 mm) were attached to the surface of the MG. During the experiment, two-dimensional video recordings of the movements of the MG were made. The coordinates of the marker centroids were obtained by computer processing of digitized images and marker displacements as a function of time were calculated. Green-Lagrange strains in two principal directions were calculated (epsilon 1, epsilon 2) for three specimens. epsilon 1 had approximately the same direction as the muscle fibers. The longitudinal strain of the fibers (20-30%) was larger than the strain of the aponeurosis (1-5%); p0.001. No significant difference was found between the values of the transverse strains of muscle fibers and aponeurosis; the value of epsilon 2 was -6 to -9% for both tissue structures.

Pompe disease is a lysosomal storage disorder caused by acid alpha-glucosidase deficiency and characterized by progressive muscle weakness. Enzyme replacement therapy (ERT) has ameliorated patients' perspectives, but reversal of skeletal muscle pathology remains a challenge. We studied pretreatment biopsies of 22 patients with different phenotypes to investigate to what extent fiber-type distribution and fiber-type-specific damage contribute to clinical diversity. Pompe patients have the same fiber-type distribution as healthy persons, but among nonclassic patients with the same GAA mutation (c.-32-13T>G), those with early onset of symptoms tend to have more type 2 muscle fibers than those with late-onset disease. Further, it seemed that the older, more severely affected classic infantile patients and the wheelchair-bound and ventilated nonclassic patients had a greater proportion of type 2x muscle fibers. However, as in other diseases, this may be caused by physical inactivity of those patients.

This study evaluates the chunking hypothesis in the context of two-element, reciprocal aiming movements. The chunking hypothesis assumes that movements toward small targets require a movement stop while movements toward large targets require a movement reversal . According to the chunking hypothesis, a movement reversal allows for a functional coupling or linkage between the forward and backward movement such that braking energy generated by antagonist activity in the forward movement is stored as elastic energy and re-utilized as acceleration energy in the backward movement (Guiard, 1993). An experiment is reported which examined movement kinematics of left-right reversal movements using four different target combinations; small-small, small-large, large-large, and large-small, for left and right targets, respectively. The results accommodated predictions derived from the chunking hypothesis. Several implications for motor control theory are discussed.

We previously demonstrated that hexokinase (HK) II plays a key role in the pathophysiology of ischemia-reperfusion (I/R) injury of the heart (Smeele et al. Circ Res 108: 1165–1169, 2011; Wu et al. Circ Res 108: 60–69, 2011). However, it is unknown whether HKII also plays a key role in I/R injury and healing thereafter in skeletal muscle, and if so, through which mechanisms. We used male wild-type (WT) and heterozygous HKII knockout mice (HKII+/−) and performed in vivo unilateral skeletal muscle I/R, executed by 90 min hindlimb occlusion using orthodontic rubber bands followed by 1 h, 1 day, or 14 days reperfusion. The contralateral (CON) limb was used as internal control. No difference was observed in muscle glycogen turnover between genotypes at 1 h reperfusion. At 1 day reperfusion, the model resulted in 36% initial cell necrosis in WT gastrocnemius medialis (GM) muscle that was doubled (76% cell necrosis) in the HKII+/−mice. I/R-induced apoptosis (29%) was similar between genotypes. HKII reduction eliminated I/R-induced mitochondrial Bax translocation and oxidative stress at 1 day reperfusion. At 14 days recovery, the tetanic force deficit of the reperfused GM (relative to control GM) was 35% for WT, which was doubled (70%) in HKII+/−mice, mirroring the initial damage observed for these muscles. I/R increased muscle fatigue resistance equally in GM of both genotypes. The number of regenerating fibers in WT muscle (17%) was also approximately doubled in HKII+/−I/R muscle (44%), thus again mirroring the increased cell death in HKII+/−mice at day 1 and suggesting that HKII does not significantly affect muscle regeneration capacity. Reduced HKII was also associated with doubling of I/R-induced fibrosis. In conclusion, reduced muscle HKII protein content results in impaired muscle functionality during recovery from I/R. The impaired recovery seems to be mainly a result of a greater susceptibility of HKII+/−mice to the initial I/R-induced necrosis (not apoptosis), and not a HKII-related deficiency in muscle regeneration.

We investigated whether myonuclear number increases in proportion to the increase in fiber size during maturational growth of skeletal muscle. Thoraco-abdominal muscle tissue was obtained from twenty 6-day to 15-year-old boys and girls during cardiothoracic surgery. Cross-sections were stained by anti-laminin for the basal lamina and by DAPI to identify nuclei. Basal lamina was traced on digital images to measure the fiber cross-sectional area (FCSA). Nuclei located within the basal lamina were considered myonuclei if pax7-negative and satellite cell nuclei if pax7-positive. Samples of two children were excluded from analysis because of clear signs of hypoxia as shown by positive carbonic anhydrase IX staining. Linear regression showed that FCSA increased with age by 187 mum(2) .per annum (R(2) = 0.90; P < 0.001). Satellite cell density showed a dramatic decrease in the first months of life, but this was not accompanied by an increase in myonuclei per muscle fiber cross-section. Till four years of age the number of myonuclei per muscle fiber cross-section remained relatively constant but increased thereafter. Myonuclear domain size showed a steep increase during infancy and reached adult values in the young adolescent phase. Anat Rec, 2013. (c) 2012 Wiley Periodicals, Inc.

The aim of the present study was to evaluate a fast clinical protocol to enable diffusion tensor imaging of the human forearm and assess the reproducibility of six diffusion tensor imaging parameters, i.e., the tensor eigenvalues (λ(1), λ(2), and λ(3)), mean diffusivity, fractional anisotropy, and ellipsoid eccentricity. The right forearms of 10 healthy volunteers were scanned twice, with a 1-week interval. Reproducibility of the diffusion tensor imaging parameters was interpreted using Bland-Altman plots, coefficient of repeatability, repeatability index, and the intraclass correlation coefficient. Analysis was done for three regions of interest: the whole muscle volume, flexor digitorum profundus, and extensor digitorum. The Bland-Altman analysis showed that there is good agreement between the two measurements. Based on the intraclass correlation coefficients, agreement was substantial (0.59intraclass correlation coefficient0.92) for all six parameters of the whole muscle volume and flexor digitorum profundus but only fair (0.18intraclass correlation coefficient0.64) for the extensor digitorum. Using a 7 min 40 sec scan protocol, which was well tolerated by the volunteers, the reproducibility of diffusion tensor imaging parameters was demonstrated. However, repeatability varies, depending on the region of interest and diffusion tensor imaging parameters. This should be taken into account when a longitudinal study is designed.