This study examined the influence of spinal cord injury (SCI) on affected skeletal muscle. The right vastus lateralis muscle was biopsied in 12 patients as soon as they were clinically stable (average 6 wk after SCI), and 11 and 24 wk after injury. Samples were also taken from nine able-bodied controls at two time points 18 wk apart. Surface electrical stimulation (ES) was applied to the left quadriceps femoris muscle to assess fatigue at these same time intervals. Biopsies were analyzed for fiber type percent and cross-sectional area (CSA), fiber type-specific succinic dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPDH) activities, and myosin heavy chain percent. Controls showed no change in any variable over time. Patients showed 27-56% atrophy (P = 0.000) of type I, IIa, and IIax+IIx fibers from 6 to 24 wk after injury, resulting in fiber CSA approximately one-third that of controls. Their fiber type specific SDH and GPDH activities increased (P

In this study we examined the influence of complete spinal cord injury (SCI) on affected skeletal muscle morphology within 6 months of SCI. Magnetic resonance (MR) images of the leg and thigh were taken as soon as patients were clinically stable, on average 6 weeks post injury, and 11 and 24 weeks after SCI to assess average muscle cross-sectional area (CSA). MR images were also taken from nine able-bodied controls at two time points separated from one another by 18 weeks. The controls showed no change in any variable over time. The patients showed differential atrophy (P = 0.0001) of the ankle plantar or dorsi flexor muscles. The average CSA of m. gastrocnemius and m. soleus decreased by 24% and 12%, respectively (P = 0.0001). The m. tibialis anterior CSA showed no change (P = 0.3644). As a result of this muscle-specific atrophy, the ratio of average CSA of m. gastrocnemius to m. soleus, m. gastrocnemius to m. tibialis anterior and m. soleus to m. tibialis anterior declined (P = 0.0001). The average CSA of m, quadriceps femoris, the hamstring muscle group and the adductor muscle group decreased by 16%, 14% and 16%, respectively (P< or =0.0045). No differential atrophy was observed among these thigh muscle groups, thus the ratio of their CSAs did not change (P = 0.6210). The average CSA of atrophied skeletal muscle in the patients was 45-80% of that of age- and weight-matched able-bodied controls 24 weeks after injury. In conclusion, the results of this study suggest that there is marked loss of contractile protein early after SCI which differs among affected skeletal muscles. While the mechanism(s) responsible for loss of muscle size are not clear, it is suggested that the development of muscular imbalance as well as diminution of muscle mass would compromise force potential early after SCI.

This study examined functional, biochemical, and morphological characteristics of skeletal muscle in nine multiple sclerosis (MS) patients and eight healthy controls in an effort to ascertain whether intramuscular adaptations could account for excessive fatigue in this disease. Analyses of biopsies of the tibialis anterior muscle showed that there were fewer type I fibers (66 +/- 6 vs. 76 +/- 6%), and that fibers of all types were smaller (average downward arrow26%) and had lower succinic dehydrogenase (SDH; average downward arrow40%) and SDH/alpha-glycerol-phosphate dehydrogenase (GPDH) but not GPDH activities in MS vs. control subjects, suggesting that muscle in this disease is smaller and relies more on anaerobic than aerobic-oxidative energy supply than does muscle of healthy individuals. Maximal voluntary isometric force for dorsiflexion was associated with both average fiber cross-sectional area (r = 0.71, P = 0.005) and muscle fat-free cross-sectional area by magnetic resonance imaging (r = 0.80, P < 0. 001). Physical activity, assessed by accelerometer, was associated with average fiber SDH/GPDH (r = 0.78, P = 0.008). There was a tendency for symptomatic fatigue to be inversely associated with average fiber SDH activity (r = -0.57, P = 0.068). The results of this study suggest that the inherent characteristics of skeletal muscle fibers per se and of skeletal muscle as a whole are altered in the direction of disuse in MS. They also suggest that changes in skeletal muscle in MS may significantly affect function.

This study tested that hypothesis that skeletal muscle within a year of spinal cord injury (SCI) would respond to intermittent high force loading by showing an increase in size. Three males about 46 weeks post clinically complete SCI underwent surface electrical stimulation of their left or right m. quadriceps femoris 2 days per week for 8 weeks to evoke 4 sets of ten isometric or dynamic actions each session. Conditioning increased average cross-sectional area of m. quadriceps femoris, assessed by magnetic resonance imaging, by 20+/-1% (p = 0.0103). This reversed 48 weeks of atrophy such that m. quadriceps femoris 54 weeks after SCI was the same size as when the patients were first studied 6 weeks after injury. The results suggest that skeletal muscle is remarkably responsive to intermittent, high force loading after almost one year of little if any contractile activity.

In this study we examined the influence of complete spinal cord injury (SCI) on the mechanical characteristics of skeletal muscle in vivo within 6 months of the injury. Surface electrical stimulation (ES) was applied to the left m. quadriceps femoris of patients at 6, 11 and 24 weeks after injury. Surface ES was also applied to seven able-bodied controls (AB) at two time points 18 weeks apart. ES consisted of 2 bouts of 20, 1-s isometric contractions with 2 s and 2 min of rest between contractions and bouts, respectively. The time from 20-80% of peak torque (rise time) and the half relaxation time (1/2 RT) were determined for the first and for the last few contractions. Force loss over repeat contractions was greater in SCI than AB (27% vs 95%; P = 0.0001), and did not change over the 18-week period. Rise time did not change over repeat contractions, was not different between groups, and nor did it change over the 18-week period (range: 150-172 ms). 1/2 RT showed several group differences. Overall, 1/2 RT was longer at the beginning of ES in SCI than AB [mean (SE) 133 (15) ms vs 90 (6) ms, P = 0.037]. Slowing of relaxation time with force loss over repeat contractions was found in SCI at 24 weeks after injury [167 (18) ms, P = 0.016], but not at 6 [128 (14) ms] or 11 [145 (12) ms] weeks after injury. AB, in contrast, showed prolonged relaxation times, with force loss at both time points [115 (10) ms and 113 (11) ms; P = 0.0001]. The results indicate that SCI alters the relaxation but not contractile properties of mixed skeletal muscle within the first 24 weeks of injury. Altered calcium handling and contraction-induced fiber injury are suggested to explain the slower relaxation time per se, and the prolonged relaxation with force loss observed after SCI.

. Phenotypic adaptations in human muscle fibers 6 and 24 wk after spinal cord injury. J Appl Physiol 92: 147-154, 2002; 10.1152/japplphysiol.000247.2001.-The effects of spinal cord injury (SCI) on the profile of sarco(endo) plasmic reticulum calcium-ATPase (SERCA) and myosin heavy chain (MHC) isoforms in individual vastus lateralis (VL) muscle fibers were determined. Biopsies from the VL were obtained from SCI subjects 6 and 24 wk postinjury (n ϭ 6). Biopsies from nondisabled (ND) subjects were obtained at two time points 18 wk apart (n ϭ 4). In ND subjects, the proportions of VL fibers containing MHC I, MHC IIa, and MHC IIx were 46 Ϯ 3, 53 Ϯ 3, and 1 Ϯ 1%, respectively. Most MHC I fibers contained SERCA2. Most MHC IIa fibers contained SERCA1. All MHC IIx fibers contained SERCA1 exclusively. SCI resulted in significant increases in fibers with MHC IIx (14 Ϯ 4% at 6 wk and 16 Ϯ 2% at 24 wk). In addition, SCI resulted in high proportions of MHC I and MHC IIa fibers with both SERCA isoforms (29% at 6 wk and 54% at 24 wk for MHC I fibers and 16% at 6 wk and 38% at 24 wk for MHC IIa fibers). Thus high proportions of VL fibers were mismatched for SERCA and MHC isoforms after SCI (19 Ϯ 3% at 6 wk and 36 Ϯ 9% at 24 wk) compared with only ϳ5% in ND subjects. These data suggest that, in the early time period following SCI, fast fiber isoforms of both SERCA and MHC are elevated disproportionately, resulting in fibers that are mismatched for SERCA and MHC isoforms. Thus the adaptations in SERCA and MHC isoforms appear to occur independently. fatigue; fiber type; myosin heavy chain; sarcoplasmic reticulum; vastus lateralis IN HUMANS, SPINAL CORD INJURY (SCI) results in adaptations in the physiological characteristics of the paralyzed muscles, including atrophy, loss of maximal force output, transformation toward fast phenotypic protein expression, including type II myosin heavy chain (MHC) isoforms, prolongation of relaxation time, and decreased resistance to fatigue (1, 7-11, 18, 20, 21, 30, 31, 40, 41, 43, 44, 54). The causes for the changes in relaxation time and resistance to fatigue have not been elucidated (9,10,43,44).Castro and colleagues (9) have demonstrated that both succinate dehydrogenase (SDH, a marker enzyme for oxidative capacity) and ␣-glycerophosphate dehydrogenase (GPDH, a marker enzyme for glycolytic capacity) activities were increased in human vastus lateralis (VL) muscle fibers, regardless of fiber type, of SCI individuals from 6 to 24 wk after injury. These data suggested that the increased susceptibility to fatigue after SCI in humans was not due to a deficiency in oxidative or glycolytic enzymatic activities related to ATP synthesis. These observations are supported by data from animal models of SCI showing that the activities of SDH and GPDH are elevated in soleus fibers of rats 1, 3, and 6 mo after a complete spinal cord transection (ST) (37).Fibers containing various isoforms of MHC are associated with distinct contractile characteristics, such that there is an ordered progression in contractile ...

Surgical recession enhanced range of motion and self reported function while not inducing any detrimental effects to plantarflexion strength at a 3-month followup. Post-surgically IGC subjects were more similar to healthy controls.

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