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Biomedical subjects

R R Roy

Publications and source records attributed to R R Roy.

At least 73 records · Page 4Linked to original sources

Differential response of fast hindlimb extensor and flexor muscles to exercise in adult spinalized cats.

Adult cats were spinal transected (T12-13) and maintained for approximately 6 months. Spinal cats were either not trained (N-T) or trained for 30 min/day to either step on a treadmill (Stp-T) or stand (Std-T). Spinalization resulted in a decrease in the mass and maximum tension potential of the medial gastrocnemius (MG), a fast ankle extensor. These adaptations were ameliorated in Std-T but not Stp-T cats. The maximum rate of shortening was elevated by 18 (ns), 34, and 19 (ns)% in the N-T, Std-T, and Stp-T cats, respectively, a finding consistent with a shift in the percentage of fast fibers, a decrease in the percentage of fibers expressing only type I myosin heavy chain, and an increase in myofibrillar adenosine triphosphatase activity. The shift toward a faster fiber type profile in the tibialis anterior (TA), a fast ankle flexor, was of a lesser magnitude than in the MG. There were no significant effects on the contractile properties of the TA in any group of spinal cats. The greater preservation of muscle mass, shift toward faster physiological and biochemical properties, and fatigability in the MG of Std-T than Stp-T cats suggest that factors other than the level of activation and force generation must play a role in muscle homeostasis. From a clinical perspective, the results indicate that muscles innervated by motor neurons below the level of a complete spinal cord lesion are affected differentially by specific neuromuscular activity patterns.

Animals↗

Myonuclear domains in muscle adaptation and disease.

Adult skeletal muscle fibers are among the few cell types that are truly multinucleated. Recently, evidence has accumulated supporting a role for the modulation of myonuclear number during muscle remodeling in response to injury, adaptation, and disease. These studies have demonstrated that muscle hypertrophy is associated with, and is dependent on, the addition of newly formed myonuclei via the fusion of myogenic cells to the adult myofiber, whereas muscle atrophy and disease appear to be associated with the loss of myonuclei, possibly through apoptotic-like mechanisms. Moreover, these studies also have demonstrated that myonuclear domain size, i. e., the amount of cytoplasm per myonucleus, is unchanged following the acute phase of hypertrophy but is reduced following atrophy. Together these data demonstrate that modulation of myonuclear number or myonuclear domain size (or both) is a mechanism contributing to the remodeling of adult skeletal muscle in response to alterations in the level of normal neuromuscular activity.

Adaptation, Physiological↗

Transmission of forces within mammalian skeletal muscles.

Most models of in vivo musculoskeletal function fail to take into account the diversity of force trajectories defined by muscle fiber architecture. It has been shown for many muscles, across species, that muscle fibers commonly end within muscle fascicles without reaching a myotendinous junction, and that many of these fibers show a progressive decline in cross-sectional area along the length of the muscle. The significance of these anatomical observations is that the tapering would seem to preclude forces generated at the largest cross-sectional area of the fibers being transmitted to the sarcomeres toward the ends of the tapered fiber. If all of the forces are transmitted via the sarcomeres arranged in series, those few sarcomeres at the smaller ends of the fibers must tolerate the stress exerted by the more numerous sarcomeres arranged in parallel at the portions of the fiber with larger cross-sectional areas. A logical alternative would be for forces to be transmitted laterally along the length of a fiber to the cell membrane and the extracellular matrix. Such a structural arrangement would permit an alternative force transmission vector and minimize the necessity for a precise level of force to be generated along the entire length of a fiber. There are cytoarchitectural and biochemical data demonstrating the presence of a subcellular network which is appropriately located to transmit forces from the active intracellular contractile elements to the extracellular intramuscular connective tissues. However, to fully comprehend how forces are transmitted from individual cross bridges to the tendon, it will be necessary to understand the interactions of all of the components of the muscle tendon complex from the molecular to the multicellular level. It is insufficient to know the physiology of the individual components in a restricted experimental paradigm and assume that these conditions account for the functional characteristics in vivo. Thus, the challenge is to understand how the sarcomeres and all of the associated structures transmit the forces of the whole muscle to its attachments.

Anatomy, Cross-Sectional↗

Metabolic and morphological stability of motoneurons in response to chronically elevated neuromuscular activity.

The purpose of this study was to determine the plasticity of spinal motoneuron size and succinate dehydrogenase activity in response to increased levels of neuromuscular activation and/or increased target size. The plantaris muscles of adult rats were functionally overloaded for one or 10 weeks via the removal of the soleus and gastrocnemius muscles bilaterally. In addition, one group of functionally overloaded rats at each time period was trained daily (1 h/day) on a treadmill. The plantaris muscle on one side in each rat was injected with the fluorescent tracer Nuclear Yellow two days prior to the end of the study to retrogradely label the associated motor pool. At one week, the plantaris weight was increased compared to control, whereas there was no change in motoneuron size. Succinate dehydrogenase activity was unaffected in either the muscle or motoneurons. At 10 weeks, the plantaris muscle weight was larger and the succinate dehydrogenase activity lower in the functionally overloaded rats compared to age-matched controls. Training further increased the hypertrophic response, whereas the succinate dehydrogenase activity returned to control levels. In contrast, mean motoneuron size and succinate dehydrogenase activity were similar among the three groups. These data indicate that overload of a specific motor pool, involving both an increase in activation and an increase in target size, had a minimal effect on the size or the oxidative potential of the associated motoneurons. Thus, it appears that the spinal motoneurons, unlike the muscle fibers, are highly stable over a wide range of levels of chronic neuromuscular activity.

Animals↗

Modulation of myonuclear number in functionally overloaded and exercised rat plantaris fibers.

The effects of 10 wk of functional overload (FO), with and without daily treadmill endurance training, on the cross-sectional area, myonuclear number, and myonuclear domain size of mechanically isolated single fiber segments of the adult rat plantaris were determined. The fibers were typed on the basis of high-resolution gel electrophoresis for separation of specific myosin heavy chain (MHC) isoforms and grouped as type I(+) (containing some type I MHC with or without any combination of fast MHCs), type IIa(+) (containing some type IIa with or without some type IIx and/or IIb but no type I MHC), and type IIx/b (containing only type IIx and/or IIb MHCs). Type I(+) fibers had a higher myonuclear number than did both fast types of fibers in the control and FO, but not in the FO and treadmill trained, rats. All fiber types in both FO groups had a significantly larger (36-90%) cross-sectional area and a significantly higher (61-109%) myonuclear number than did control. The average myonuclear domain size of each fiber type was similar among the three groups, except for a smaller domain size in the type IIx/b fibers of the FO compared with control. In general, these data indicate that during hypertrophy the number of myonuclei increase proportionally to the increase in fiber volume. The maintenance of myonuclear domain size near control values suggests that regulatory mechanisms exist that ensure a tight coupling between the quantity of genetic machinery and the protein requirements of a fiber.

Animals↗

Spaceflight suppresses exercise-induced release of bioassayable growth hormone.

We have reported that bed rest suppressed the release of bioassayable growth hormone (BGH) that normally occurs after an acute bout of unilateral plantar flexor exercise (G. E. McCall, C. Goulet, R. E. Grindeland, J. A. Hodgson, A. J. Bigbee, and V. R. Edgerton. J. Appl. Physiol. 83: 2086-2090, 1997). In the present study, the effects of spaceflight on the hormonal responses to this exercise protocol were examined. Four male astronauts on the National Aeronautics and Space Administration Shuttle Transport System (STS-78) mission completed the exercise protocol before, during, and after a 17-day spaceflight. The maximal voluntary contraction torque output at the onset of exercise was similar on all test days. Before spaceflight, plasma BGH increased 114-168% from pre- to postexercise. During spaceflight and after 2 days recovery at normal gravity (1 G), the BGH response to exercise was absent. After 4 days of recovery, this response was restored. Plasma concentrations of immunoassayable growth hormone were similar at all time points. The preexercise plasma immunoassayable insulin-like growth factor I (IGF-I) levels were elevated after 12 or 13 days of microgravity, and a approximately 7% postexercise IGF-I increase was independent of this spaceflight effect. The suppression of the BGH response to exercise during spaceflight indicates that some minimum level of chronic neuromuscular activity and/or loading is necessary to maintain a normal exercise-induced BGH release. Moreover, these results suggest that there is a muscle afferent-pituitary axis that can modulate BGH release.

Adult↗

Myonuclear domain and myosin phenotype in human soleus after bed rest with or without loading.

After 2 or 4 mo of bed rest (6 degrees head-down tilt) and 1 mo of ambulation, there was a tendency toward a higher percentage of fibers expressing fast myosin heavy chain (MHC) isoforms and a de novo appearance of fibers coexpressing type I+IIa+IIx and IIa+IIx MHC in human soleus fibers. After 2 and 4 mo of bed rest, the mean size of type I fibers decreased by 12 (P > 0.05) and 39%, respectively. Because myonuclear number/mm of fiber length was unchanged, myonuclear domain was smaller after bed rest than before. The mean size and myonuclear domain of type I fibers were largest after 1 mo of recovery. The effects of wearing an antigravity device (Penguin suit), which had a modest but continuous resistance at the knee and ankle (Penguin-1) or knee resistance without loading on the ankle (Penguin-2), for 10 consecutive h/day were determined during 2 mo of bed rest. Mean fiber sizes in Penguin-1, but not Penguin-2, group were maintained at or above pre-bed-rest levels, whereas neither group showed phenotype changes. Myonuclear domain in type I fibers was larger in Penguin-1 and smaller in Penguin-2 group post- compared with pre-bed rest, indicating that a single daily 10-h bout of modest muscle loading can prevent bed-rest-induced soleus fiber atrophy but has minimal effect on myosin phenotype. The specific adaptive cellular strategies involved may be a function of the duration and magnitude of the adaptive stimulus as well as the immediate activity history of the fiber before the newly changed functional demands.

Adult↗

Retention of hindlimb stepping ability in adult spinal cats after the cessation of step training.

Adult spinal cats were trained to perform bipedal hindlimb locomotion on a treadmill for 6-12 wk. After each animal acquired the ability to step, locomotor training was withheld, and stepping was reexamined 6 and 12 wk after training ended. The performance characteristics, hindlimb muscle electromyographic activity patterns, and kinematic characteristics of the step cycle that were acquired with training were largely maintained when training was withheld for 6 wk. However, after 12 wk without training, locomotor performance declined, i.e., stumbling was more frequent, and the ability to consistently execute full weight-bearing steps at any treadmill speed decreased. In addition, the height that the paw was lifted during the swing phase decreased, and a smaller range of extension in the hindlimbs occurred during the E3 phase of stance. When three of the spinal cats underwent 1 wk of retraining, stepping ability was regained more rapidly than when trained initially. The finding that stepping ability in trained adult spinal cats can persist for 6 wk without training provides further evidence that training-induced enhancement of stepping is learned in the spinal cats and that a memory of the enhanced stepping is stored in the spinal networks. However, it appears that the spinal cord can forget how to consistently execute stepping if that task is not practiced for 12 wk. The more rapid learning that occurred with retraining is also consistent with a learning phenomenon. These results in conjunction with our earlier findings suggest that the efficacy of the neural pathways that execute a motor task is highly dependent on the periodic activation of those pathways in a sequence compatible with that motor task.

Animals↗

Effects of spaceflight on rhesus quadrupedal locomotion after return to 1G.

Effects of spaceflight on Rhesus quadrupedal locomotion after return to 1G. Locomotor performance, activation patterns of the soleus (Sol), medial gastrocnemius (MG), vastus lateralis (VL), and tibialis anterior (TA) and MG tendon force during quadrupedal stepping were studied in adult Rhesus before and after 14 days of either spaceflight (n = 2) or flight simulation at 1G (n = 3). Flight simulation involved duplication of the spaceflight conditions and experimental protocol in a 1G environment. Postflight, but not postsimulation, electromyographic (EMG) recordings revealed clonus-like activity in all muscles. Compared with preflight, the cycle period and burst durations of the primary extensors (Sol, MG, and VL) tended to decrease postflight. These decreases were associated with shorter steps. The flexor (TA) EMG burst duration postflight was similar to preflight, whereas the burst amplitude was elevated. Consequently, the Sol:TA and MG:TA EMG amplitude ratios were lower following flight, reflecting a "flexor bias." Together, these alterations in mean EMG amplitudes reflect differential adaptations in motor-unit recruitment patterns of flexors and extensors as well as fast and slow motor pools. Shorter cycle period and burst durations persisted throughout the 20-day postflight testing period, whereas mean EMG returned to preflight levels by 17 days postflight. Compared with presimulation, the simulation group showed slight increases in the cycle period and burst durations of all muscles. Mean EMG amplitude decreased in the Sol, increased in the MG and VL, and was unchanged in the TA. Thus adaptations observed postsimulation were different from those observed postflight, indicating that there was a response unique to the microgravity environment, i.e., the modulations in the nervous system controlling locomotion cannot merely be attributed to restriction of movement but appear to be the result of changes in the interpretation of load-related proprioceptive feedback to the nervous system. Peak MG tendon force amplitudes were approximately two times greater post- compared with preflight or presimulation. Adaptations in tendon force and EMG amplitude ratios indicate that the nervous system undergoes a reorganization of the recruitment patterns biased toward an increased recruitment of fast versus slow motor units and flexor versus extensor muscles. Combined, these data indicate that some details of the control of motor pools during locomotion are dependent on the persistence of Earth's gravitational environment.

Adaptation, Psychological↗

Hindlimb locomotor and postural training modulates glycinergic inhibition in the spinal cord of the adult spinal cat.

Adult spinal cats were trained initially to perform either bipedal hindlimb locomotion on a treadmill or full-weight-bearing hindlimb standing. After 12 wk of training, stepping ability was tested before and after the administration (intraperitoneal) of the glycinergic receptor antagonist, strychnine. Spinal cats that were trained to stand after spinalization had poor locomotor ability as reported previously, but strychnine administration induced full-weight-bearing stepping in their hindlimbs within 30-45 min. In the cats that were trained to step after spinalization, full-weight-bearing stepping occurred and was unaffected by strychnine. Each cat then was retrained to perform the other task for 12 wk and locomotor ability was retested. The spinal cats that were trained initially to stand recovered the ability to step after they received 12 wk of treadmill training and strychnine was no longer effective in facilitating their locomotion. Locomotor ability declined in the spinal cats that were retrained to stand and strychnine restored the ability to step to the levels that were acquired after the step-training period. Based on analyses of hindlimb muscle electromyographic activity patterns and kinematic characteristics, strychnine improved the consistency of the stepping and enhanced the execution of hindlimb flexion during full-weight-bearing step cycles in the spinal cats when they were trained to stand but not when they were trained to step. The present findings provide evidence that 1) the neural circuits that generate full-weight-bearing hindlimb stepping are present in the spinal cord of chronic spinal cats that can and cannot step; however, the ability of these circuits to interpret sensory input to drive stepping is mediated at least in part by glycinergic inhibition; and 2) these spinal circuits adapt to the specific motor task imposed, and that these adaptations may include modifications in the glycinergic pathways that provide inhibition.

Animals↗

Fiber size and myosin phenotypes of selected Rhesus hindlimb muscles after a 14-day spaceflight.

Open muscle biopsies were obtained from Rhesus soleus (slow ankle extensor), medial gastrocnemius (fast ankle extensor) and tibialis anterior (fast ankle flexor) muscles before and after either a 14-day spaceflight (BION 11, n=2) or ground-based flight simulation (n=3) and in time-matched controls (n=5). Fiber type distribution (immunohistochemistry), myosin heavy chain (MHC) composition (gel electrophoresis) and fiber size were determined. There was a large amount of inter-animal variability and there were no significant pre-post differences for any variable under any condition for any muscle studied. However, each muscle showed trends towards adaptation. Based on the immunohistochemical analyses, the percentage of type I fibers in the soleus was 68 and 86% in pre and 43 and 70% in post biopsies of the simulation and flight groups. The number of hybrid (containing both fast and slow MHC) fibers increased in both groups. MHC composition changed in a similar direction. Type I and hybrid fibers were 23 and 31% smaller after than before flight. In the medial gastrocnemius, type I fibers were 16, 14 and 32% smaller in post compared to pre biopsies in control, simulation and flight Rhesus. In the tibialis anterior, type I fibers were approximately 14% smaller in post- than pre-flight biopsies. As expected the soleus, a slow anti-gravity muscle, was most affected after 14 days of weightlessness. Further, slow fibers in each muscle were more responsive to microgravity than fast fibers. All changes, however, were smaller than those observed in rats after the same duration of flight. This differential effect may be related to the partial restraint of Rhesus in the chaired position compared to the free-floating position of rats in the cage and/or to differences in the contractile protein turnover rates between species.

Animals↗

Distribution of muscle spindles in a simply structured muscle: integrated total sensory representation.

BACKGROUND: The distribution of muscle spindles (Sps) in a small muscle of simple architecture, the capsularis at the cat's hip joint, was quantified to reveal the patterns of proprioceptive representation in the transverse and sagittal planes as well as to model the effect a local disturbance in muscle length would have on total Sp discharge. METHODS: Locations in serial cross-sections of the 32 and 38 Sps in 2 muscles, 1 perfused with the hip joint flexed and the other extended, were plotted, and their patterns of integrated sensitivity calculated assuming that (1) the discharge rate of a Sp afferent varies linearly with change in length along the Sp's axis, and (2) that within a local disturbance produced by contraction of a motor unit (MU), lengths decrease either linearly or as the square of the distance from its center. RESULTS: The isomeric pattern of "integrated, total Sp representation on cross-section" showed two peaks of sensitivity in the half of the muscle that had been next to the joint capsule, offset by low representation in a small, central area and along the extensive zone bordering the laterally facing "superficial surface." The equivalent radius of an idealized symmetrical MU territory was estimated from distributions of the few fast, oxidative-glycolytic fibers found in two muscles, and the effect of a MU's contraction on net Sp discharge predicted when the unit was positioned at distinctive sites within the pattern. As an index of Ia and II afferent representation in the sagittal plane, the distribution of the nucleated regions of Sps and the summed lengths of segments of Sp axial bundles and capsules, respectively, within successive 1-mm segments of the muscle were graphed. CONCLUSIONS: The longitudinal representation and structure of the muscle are not suited for reflex adjustment of differences in length along the muscle. The isomeric pattern of high relief in the transverse plane suggests that in this approximately 0.2 g muscle, the localization of myotatic reflexes might be accommodated but the need for adjustment in activation of MUs seems minimal. This is because the muscle is not compartmentalized, its fibers extend between the muscle's origin and insertion, their angle of pinnation is low, and greater than 90% are of slow type. The distribution of Sps is consistent with gauging length of the entire muscle and hence angulation at the hip joint.

Animals↗

Training effects on soleus of cats spinal cord transected (T12-13) as adults.

Adult spinal cord transected (T12-13) cats were trained for 30 min/day, 5 days/week to either step on a treadmill (Stp-T) or stand (Std-T) for approximately 5 months. Training ameliorated soleus atrophy and enhanced maximum force capability compared to nontrained (N-T) spinal cats, with Stp-T being significantly different from N-T. Isometric twitch speed and maximum rate of shortening were unaffected by training; the soleus of all spinal groups was significantly faster than control. There was an elevation in myosin adenosine triphosphatase activity and a shift toward faster myosin heavy chain and fiber type compositions in N-T and Std-T, but not Stp-T cats. Thus, rhythmical activity involving muscle length and force changes (stepping) was more effective than a similar amount of a more static activity (standing). This specificity related to the type of training should be considered when developing rehabilitative strategies following spinal cord injury.

Animals↗

Effects of inactivity on myosin heavy chain composition and size of rat soleus fibers.

Myosin heavy chain (MHC) and fiber size properties of the adult rat soleus were determined after 4-60 days of complete inactivity, i.e., lumbar spinal cord isolation. Soleus atrophy was rapid and progressive, i.e., 25% and 64% decrease in weight and 33% and 75% decrease in fiber size after 4 and 60 days of inactivity, respectively. Changes in MHC occurred at a slower rate than the atrophic response. After 15 days there was de novo expression of type IIx MHC (approximately 10%). By 60 days, type IIx MHC accounted for 33% of the total MHC content, and 7% of the fibers contained only type IIx MHC. The relative amount of type I MHC was reduced from 93% in control to 49% after 60 days of inactivity. Therefore, the effects of 60 days of inactivity suggest that during this time period at least 75% of fiber size and approximately 40% of type I MHC composition of the adult rat soleus can be attributed to activation-related events.

Animals↗

Cyclical passive stretch influences the mechanical properties of the inactive cat soleus.

The effects of cyclical, passive manipulation (PM, 30 min day(-1), 5 days week(-1) for 6 months) mimicking the length excursions observed during stepping on the mechanical and associated biochemical properties of the inactive cat soleus muscle were determined in five cats. Inactivity was produced via spinal cord isolation (SI), i.e. complete spinal cord transections at low thoracic and high sacral levels and bilateral dorsal rhizotomy between the transection sites. Passive manipulation was administered to one leg of each SI cat. Compared with normal controls, SI resulted in approximately 70% decrease in weight, an 80% decrease in maximum tetanic tension (Po) and an approximately 100% increase in maximum rate of shortening (Vmax) and myosin adenosine triphosphatase (mATPase) activity of the soleus. The passive manipulation regime partially ameliorated these effects. When compared with the control SI soleus, the SI-PM soleus weight and maximum tetanic tension were 12 and 21% higher, respectively, and the Vmax and mATPase activity 21 and 12% (p > 0.05) lower, respectively. Thus, inactivity resulted in a smaller and faster muscle, whereas passive manipulation for only 30 min a day tended to maintain these properties closer to normal control values. The results suggest a potential therapeutic effect of short bouts of cyclical, passive manipulation on otherwise inactive skeletal muscles.

Animals↗

Maintenance of myonuclear domain size in rat soleus after overload and growth hormone/IGF-I treatment.

The purpose of this study was to determine the effects of functional overload (FO) combined with growth hormone/insulin-like growth factor I (GH/IGF-I) administration on myonuclear number and domain size in rat soleus muscle fibers. Adult female rats underwent bilateral ablation of the plantaris and gastrocnemius muscles and, after 7 days of recovery, were injected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receiving saline vehicle served as controls (Con group). Muscle wet weight was 32% greater in the FO than in the Con group: 162 +/- 8 vs. 123 +/- 16 mg. Muscle weight in the FO + GH/IGF-I group (196 +/- 14 mg) was 59 and 21% larger than in the Con and FO groups, respectively. Mean soleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 +/- 445 microm2) was increased compared with the Con (2,044 +/- 108 microm2) and FO (2,267 +/- 301 microm2) groups. The difference in fiber size between the FO and Con groups was not significant. Mean myonuclear number increased in FO (187 +/- 15 myonuclei/mm) and FO + GH/IGF-I (217 +/- 23 myonuclei/mm) rats compared with Con (155 +/- 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume per myonucleus (myonuclear domain) was similar across groups. These results demonstrate that the larger mean muscle weight and fiber cross-sectional area occurred when FO was combined with GH/IGF-I administration and that myonuclear number increased concomitantly with fiber volume. Thus there appears to be some mechanism(s) that maintains the myonuclear domain when a fiber hypertrophies.

Animals↗

Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary.

There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

Animals↗