Effects of treadmill running and limb immobilization on knee cartilage degeneration and locomotor joint kinematics in rats following knee meniscal transection.

OBJECTIVE: This study examined the effects of reduced and elevated weight bearing on post-traumatic osteoarthritis (PTOA) development, locomotor joint kinematics, and degree of voluntary activity in rats following medial meniscal transection (MMT). DESIGN: Twenty-one adult rats were subjected to MMT surgery of the left hindlimb and then assigned to one of three groups: (1) regular (i.e., no intervention), (2) hindlimb immobilization, or (3) treadmill running. Sham surgery was performed in four additional rats. Voluntary wheel run time/distance was measured, and 3D hindlimb kinematics were quantified during treadmill locomotion using biplanar radiography. Rats were euthanized 8 weeks after MMT or sham surgery, and the microstructure of the tibial cartilage and subchondral bone was quantified using contrast enhanced micro-CT. RESULTS: All three MMT groups showed signs of PTOA (full-thickness lesions and/or increased cartilage volume) compared to the sham group, however the regular and treadmill-running groups had greater osteophyte formation than the immobilization group. For the immobilization group, increased volume was only observed in the anterior region of the cartilage. The treadmill-running group demonstrated a greater knee varus angle at mid-stance than the sham group, while the immobilization group demonstrated greater reduction in voluntary running than all the other groups at 2 weeks post-surgery. CONCLUSIONS: Elevated weight-bearing via treadmill running at a slow/moderate speed did not accelerate PTOA in MMT rats when compared to regular weight-bearing. Reduced weight-bearing via immobilization may attenuate overall PTOA but still resulted in regional cartilage degeneration. Overall, there were minimal differences in hindlimb kinematics and voluntary running between MMT and sham rats.

Prednisolone treatment and restricted physical activity further compromise bone of mdx mice.

OBJECTIVES: The purpose of this study was to determine the extent to which prednisolone treatment and restricted physical activity caused deleterious changes in inherently compromised mdx bone. METHODS: Four week-old male mdx mice (n=36) were treated for 8-wk either with or without prednisolone (0.8-1.3 mg/kg/d) and were housed in traditional or small cages (restricted activity). Tibial bone strength, geometry, and intrinsic material properties were assessed at the mid-shaft by three-point bending and micro-computed tomography (µCT). RESULTS: Three-point bending results showed that both prednisolone and restricted activity reduced bone strength (7%), however stiffness was only reduced in restricted-activity mice. µCT analyses showed that cortical bone area and cortical thickness were 13% smaller in restricted-activity mice, and may have accounted for their compromised bone strength. Intrinsic material properties, including volumetric bone mineral density (vBMD) and modulus of elasticity, were not impacted by either treatment, however, vBMD tended to be lower in restricted-activity mice (p=0.06). CONCLUSIONS: These data show that prednisolone treatment and restricted physical activity independently accentuate reductions in the strength and geometry of mdx bone, but do not influence intrinsic material properties.

Functional recovery of the plantarflexor muscle group after hindlimb unloading in the rat.

Research into skeletal muscle's response to hindlimb unloading (HU) of the rodent has focused on that of the markedly affected slow-twitch anti-gravity muscles (e.g., soleus). However, the ability of the animal to locomote following HU should be best determined by the in vivo functional properties of the muscle groups involved and, to our knowledge, this has not been investigated. Our objective was to determine how the in vivo functional properties of the rat ankle plantarflexor group change after 28 days of HU and during a subsequent 28-day recovery. Rats ( n=48) were unloaded for 28 days after which they were either tested immediately or allowed to recover for 7, 14, or 28 days before being tested. Control rats ( n=61) were tested at comparable times. In vivo functional properties of the ankle plantarflexors were assessed under anesthesia using an isokinetic dynamometer and included determination of the isometric torque-frequency relationship, the concentric torque-ankle angular velocity relationship, and fatigability. Immediately after HU, plantarflexor muscle weight was reduced by 24% but isometric torque production was reduced by 7-9% only at > or =100 Hz and concentric torque production was not significantly affected. However, after 7 days of recovery, in vivo function was more adversely affected; isometric and concentric torques were reduced by 12-33% and 16-36%, respectively, relative to control levels. In vivo plantarflexor function was recovered by 14 days. In conclusion, 28 days of HU has minor adverse effects on the in vivo function of the rat ankle plantarflexors. During the first week of recovery from HU, injury apparently occurs to the plantarflexors resulting in a transient impairment of functional capacity.

Variable frequency trains enhance torque independent of stimulation amplitude.

AIM: Variable frequency trains have been reported to enhance force of fatigued human skeletal muscle. More rapid calcium turnover and/or enhanced stiffness may be responsible for the augmented torque-time integral during surface stimulation at moderate amplitude. In contrast, it has recently been suggested that variable frequency train enhancement occurs only at low forces as a result of preferential stimulation of fast fibres and/or altered motor unit recruitment. If correct, this would limit the practical benefit of variable frequency trains. Accordingly, we tested the hypothesis that torque augmentation by variable frequency trains in fatigued skeletal muscle was independent of stimulation amplitude. METHODS: The m. quadriceps femoris of six males was stimulated with constant frequency trains (six 200-micros square waves separated by 70 ms) or variable frequency trains (first interpulse interval 5 ms) at an amplitude that initially evoked approximately 25 or approximately 50% of maximal voluntary isometric torque. RESULTS: After 180 constant frequency trains (50% duty cycle), isometric peak torque decreased approximately 63%. In fatigued muscle, variable frequency trains enhanced the torque-time integral by approximately 23% over that for constant frequency trains and this effect was independent of stimulation amplitude. This was due to greater peak torque and less slowing of rise time. CONCLUSION: These responses show that the torque-time integral can be enhanced at both moderate and high stimulation amplitudes. As such, it is suggested that neither recruitment nor preferential activation of fast muscle is responsible for the "catch-like" property that can be demonstrated in fatigued human skeletal muscle.

Excitation-contraction uncoupling: major role in contraction-induced muscle injury.

The mechanisms that account for the strength loss after contraction-induced muscle injury remain controversial. We present data showing that (1) most of the early strength loss results from a failure of excitation-contraction coupling and (2) a slow loss of contractile protein in the days after injury prolongs the recovery time.

Altered primary myogenesis in NFATC3(-/-) mice leads to decreased muscle size in the adult.

Signal transduction pathways involving calcineurin and its downstream effector NFAT have been implicated in regulating myogenesis. Several isoforms of NFAT exist that may differentially contribute to regulating skeletal muscle physiology. The purpose of this study was to determine the role of the NFATC3 isoform in skeletal muscle development. Adult mice lacking NFATC3 have reduced muscle mass compared to control mice. The smaller size of the muscles is not due to atrophy or blunted myofiber growth, but rather to a reduced number of myofibers. This reduction in myofiber number is not limited to a specific fiber type nor are the proportions of fiber types altered. The lower fiber number found in the adult NFATC3(-/-) mice is a consequence of impaired muscle development during embryogenesis. Immunohistochemical studies of E15 EDL muscles indicate that the total number of primary myofibers is decreased in NFATC3(-/-) embryos. At E17.5 no further decrease in primary myofiber number occurs; the size and organization of the myofibers are unaltered, and secondary myogenesis proceeds normally, suggesting a role for NFATC3 during early events in primary myogenesis. These results suggest a heretofore unknown role for the transcription factor NFAT in early skeletal muscle development.

Muscle activation and the slow component rise in oxygen uptake during cycling.

PURPOSE: During constant-rate high-intensity exercise, a steady state for oxygen uptake (VO2) is not achieved and, after the initial rapid increase, VO2 continues to increase slowly. The mechanism underlying the slow-component rise in VO2 during high-intensity exercise is unknown. It has been hypothesized that increased muscle use may be a contributing factor, but only limited electromyograph (EMG) data are available supporting this hypothesis. The purpose of this study was to determine whether there is an association between the VO2 slow component and muscle use assessed by contrast shifts in magnetic resonance images (magnetic resonance imaging (MRI)). METHODS: The VO2 slow component was measured in 16 subjects during two 15-min bouts of cycling performed at high and low intensities. EMG and MRI transverse relaxation times (T2) were obtained after 3 and 15 min to determine muscle activity at each intensity. RESULTS: Low-intensity cycling produced no VO2 slow component, and no increases in muscle activity, except for a small increase (P < 0.05) in the T2 of the vastus lateralis. During high-intensity cycling, VO2, T2 of the vastus lateralis, rectus femoris and whole leg, and EMG activity and median power frequency of the vastus lateralis rose significantly (P < 0.05) from 3 to 15 min. Percent increases in VO2 and muscle T2 were related during high-intensity cycling (r = 0.63), but not during low-intensity cycling (r = 0.00). CONCLUSION: We conclude that increased muscle use is in part responsible for the slow component rise in oxygen uptake. The results support the hypothesis that during constant-rate exercise at intensities above lactate threshold, progressively greater use of fast-twitch motor units increases energy demand and causes concomitant progressive increases in VO2 and lactate.

Strength loss after eccentric contractions is unaffected by creatine supplementation.

This study's objective was to determine whether 14 days of dietary creatine supplementation preceding an injurious bout of eccentric contractions affect the in vivo strength loss of mouse anterior crural muscles. Three groups of nine mice each were fed a meal diet for 14 days, one group at each of three levels of creatine supplementation (i.e., 0, 0.5, and 1% creatine). Electrically stimulated concentric, isometric, and eccentric contraction torques produced about the ankle were measured both before and after a bout of 150 eccentric contractions. Tibialis anterior muscle creatine concentration was significantly increased by the supplementation, being 12% higher in the mice fed the 1% creatine diet compared with control mice. After the bout of eccentric contractions, the reductions in torque (i.e., 46-58%) were similar for the isometric contraction, all eccentric contractions, and the slow (i.e., /= 0.62). In conclusion, a moderate increase in muscle creatine concentration induced by dietary supplementation in mice does not affect the strength loss after eccentric contractions.

Decreased EMG median frequency during a second bout of eccentric contractions.

PURPOSE: Others have reported preferential recruitment of fast motor units in muscles during performance of eccentric contractions and there is evidence that fast muscle fibers are more susceptible to eccentric contraction-induced injury. We tested the hypothesis that during a second bout of maximal eccentric contractions 1 wk after the first, there would be a reduction in the electromyographic (EMG) median frequency (MF) with minimal change in the EMG root-mean-square (RMS), indicating greater reliance on slower motor units. This could provide an explanation for the enhanced resistance to eccentric contraction-induced injury after a single bout of eccentric exercise. METHODS: Human subjects performed 50 maximal voluntary eccentric (N = 10) or concentric (N = 10) contractions of the anterior crural muscles on two occasions separated by 1 wk. To determine whether MF changes during the second bout could be a consequence of injury to fibers in fast motor units, the anterior crural muscles of mice were electrically stimulated to perform 50 maximal eccentric (N = 10) or concentric (N = 9) contractions on two occasions separated by 1 wk. In both the humans and mice, torque production and tibialis anterior muscle RMS and MF were measured during the two exercise bouts. RESULTS: In human tibialis anterior muscle, MF was 30% lower (P < 0.01) during the second eccentric bout although RMS was the same. In the mice, RMS and MF were unchanged at any time after the first eccentric bout despite torque deficits similar to those observed in the humans. CONCLUSIONS: The data indicate that with repetition of maximal voluntary eccentric contractions, there is an increased activation of slow motor units and a concomitant decrease in activation of fast units.

Mechanical loading attenuates bone loss due to immobilization and calcium deficiency.

Our purpose was to determine the effects of a mechanical loading intervention on mass, geometry, and strength of rat cortical bone during a period of disuse concurrent with calcium deficiency (CD). Adult female rats were assigned to unilateral hindlimb immobilization, immobilized-loaded, or control (standard chow, 1.85% calcium) treatments. Both immobilized groups were fed a CD rat chow (0.01% calcium) to induce high bone turnover. Three times weekly, immobilized-loaded rats were subjected to 36 cycles of 4-point bending of the immobilized lower leg. After 6 wk, the immobilized rats exhibited decreased tibial shaft bone mineral density (-12%), ultimate load (-19%), and stiffness (-20%; tested in 3-point bending to failure) vs. control rats. Loading prevented this decline in bone density and attenuated decreases in ultimate load and stiffness. Elastic modulus was unaffected by disuse or loading. Bone cross-sectional area in the immobilized-loaded rats was equivalent to that of control animals, even though endocortical resorption continued unabated. On the medial periosteum, percent mineralizing surface doubled vs. that in immobilized rats. This loading regimen stimulated periosteal mineralization and maintained bone mineral density, thereby attenuating the loss in bone strength incurred with disuse and concurrent calcium deficiency.

Intracellular Ca2+ transients in mouse soleus muscle after hindlimb unloading and reloading.

The objective of this study was to determine whether altered intracellular Ca(2+) handling contributes to the specific force loss in the soleus muscle after unloading and/or subsequent reloading of mouse hindlimbs. Three groups of female ICR mice were studied: 1) unloaded mice (n = 11) that were hindlimb suspended for 14 days, 2) reloaded mice (n = 10) that were returned to their cages for 1 day after 14 days of hindlimb suspension, and 3) control mice (n = 10) that had normal cage activity. Maximum isometric tetanic force (P(o)) was determined in the soleus muscle from the left hindlimb, and resting free cytosolic Ca(2+) concentration ([Ca(2+)](i)), tetanic [Ca(2+)](i), and 4-chloro-m-cresol-induced [Ca(2+)](i) were measured in the contralateral soleus muscle by confocal laser scanning microscopy. Unloading and reloading increased resting [Ca(2+)](i) above control by 36% and 24%, respectively. Although unloading reduced P(o) and specific force by 58% and 24%, respectively, compared with control mice, there was no difference in tetanic [Ca(2+)](i). P(o), specific force, and tetanic [Ca(2+)](i) were reduced by 58%, 23%, and 23%, respectively, in the reloaded animals compared with control mice; however, tetanic [Ca(2+)](i) was not different between unloaded and reloaded mice. These data indicate that although hindlimb suspension results in disturbed intracellular Ca(2+) homeostasis, changes in tetanic [Ca(2+)](i) do not contribute to force deficits. Compared with unloading, 24 h of physiological reloading in the mouse do not result in further changes in maximal strength or tetanic [Ca(2+)](i).

Uncoupling of in vivo torque production from EMG in mouse muscles injured by eccentric contractions.

1. The main objective of this study was to determine whether eccentric contraction-induced muscle injury causes impaired plasmalemmal action potential conduction, which could explain the injury-induced excitation-contraction coupling failure. Mice were chronically implanted with stimulating electrodes on the left common peroneal nerve and with electromyographic (EMG) electrodes on the left tibialis anterior (TA) muscle. The left anterior crural muscles of anaesthetized mice were stimulated to perform 150 eccentric (ECC) (n = 12 mice) or 150 concentric (CON) (n = 11 mice) contractions. Isometric torque, EMG root mean square (RMS) and M-wave mean and median frequencies were measured before, immediately after, and at 1, 3, 5 and 14 days after the protocols. In parallel experiments, nicotinic acetylcholine receptor (AChR) concentration was measured in TA muscles to determine whether the excitation failure elicited a denervation-like response. 2. Immediately after the ECC protocol, torque was reduced by 47-89 %, while RMS was reduced by 9-21 %; the RMS decrement was not different from that observed for the CON protocol, which did not elicit large torque deficits. One day later, both ECC and CON RMS had returned to baseline values and did not change over the next 2 weeks. However, torque production by the ECC group showed a slow recovery over that time and was still depressed by 12-30 % after 2 weeks. M-wave mean and median frequencies were not affected by performance of either protocol. 3. AChR concentration was elevated by 79 and 368 % at 3 and 5 days, respectively, after the ECC protocol; AChR concentration had returned to control levels 2 weeks after the protocol. At the time of peak AChR concentration in the ECC protocol muscles (i.e. 5 days), AChR concentration in CON protocol muscles was not different from the control level. 4. In conclusion, these data demonstrate no major role for impaired plasmalemmal action potential conduction in the excitation-contraction coupling failure induced by eccentric contractions. Additionally, a muscle injured by eccentric contractions shows a response in AChR concentration similar to a transiently denervated muscle.

Measurement tools used in the study of eccentric contraction-induced injury.

The objective of this review is to evaluate the measurement tools currently used in the study of eccentric contraction-induced muscle injury, with emphasis on their usefulness for quantifying the magnitude and duration of the injury and as indicators of muscle functional deficits. In studies in humans, it was concluded that measurements of maximal voluntary contraction torque and range of motion provide the best methods for quantifying muscle injury. Similarly, in animal studies, the in vitro measurement of electrically elicited force under isometric conditions was considered to be the best of the measurement tools currently in use. For future studies, more effort should be put into measuring other contractile parameters (e.g. force/torque-velocity and force/torque-length relationships maximal shortening velocity and fatigue susceptibility) that may reflect injury-induced functional impairments. The use of histology, ratings of soreness and the measurement of blood or bath levels of myofibre proteins should be discouraged for purposes of quantifying muscle injury and/or functional impairment.

Crystallography & NMR system: A new software suite for macromolecular structure determination.

A new software suite, called Crystallography & NMR System (CNS), has been developed for macromolecular structure determination by X-ray crystallography or solution nuclear magnetic resonance (NMR) spectroscopy. In contrast to existing structure-determination programs, the architecture of CNS is highly flexible, allowing for extension to other structure-determination methods, such as electron microscopy and solid-state NMR spectroscopy. CNS has a hierarchical structure: a high-level hypertext markup language (HTML) user interface, task-oriented user input files, module files, a symbolic structure-determination language (CNS language), and low-level source code. Each layer is accessible to the user. The novice user may just use the HTML interface, while the more advanced user may use any of the other layers. The source code will be distributed, thus source-code modification is possible. The CNS language is sufficiently powerful and flexible that many new algorithms can be easily implemented in the CNS language without changes to the source code. The CNS language allows the user to perform operations on data structures, such as structure factors, electron-density maps, and atomic properties. The power of the CNS language has been demonstrated by the implementation of a comprehensive set of crystallographic procedures for phasing, density modification and refinement. User-friendly task-oriented input files are available for nearly all aspects of macromolecular structure determination by X-ray crystallography and solution NMR.

E-C coupling failure in mouse EDL muscle after in vivo eccentric contractions.

The objectives of this research were to determine the contribution of excitation-contraction (E-C) coupling failure to the decrement in maximal isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles after eccentric contractions and to elucidate possible mechanisms. The left anterior crural muscles of female ICR mice (n = 164) were injured in vivo with 150 eccentric contractions. Po, caffeine-, 4-chloro-m-cresol-, and K+-induced contracture forces, sarcoplasmic reticulum (SR) Ca2+ release and uptake rates, and intracellular Ca2+ concentration ([Ca2+]i) were then measured in vitro in injured and contralateral control EDL muscles at various times after injury up to 14 days. On the basis of the disproportional reduction in Po (approximately 51%) compared with caffeine-induced force (approximately 11-21%), we estimate that E-C coupling failure can explain 57-75% of the Po decrement from 0 to 5 days postinjury. Comparable reductions in Po and K+-induced force (51%), and minor reductions (0-6%) in the maximal SR Ca2+ release rate, suggest that the E-C coupling defect site is located at the t tubule-SR interface immediately after injury. Confocal laser scanning microscopy indicated that resting [Ca2+]i was elevated and peak tetanic [Ca2+]i was reduced, whereas peak 4-chloro-m-cresol-induced [Ca2+]i was unchanged immediately after injury. By 3 days postinjury, 4-chloro-m-cresol-induced [Ca2+]i became depressed, probably because of decreased SR Ca2+ release and uptake rates (17-31%). These data indicate that the decrease in Po during the first several days after injury primarily stems from a failure in the E-C coupling process.

A stimulating nerve cuff for chronic in vivo measurements of torque produced about the ankle in the mouse.

Specific muscle training and chronic contractile measurements are difficult in rodents, especially in the mouse. The primary reason for this is the lack of a means for stimulating the motor nerve that does not damage the nerve and that permits reproducible measurements of contractility. In this paper, we describe procedures for the construction and implantation of a stimulating nerve cuff for use on the mouse common peroneal nerve. We demonstrate that nerve cuff implantation success rates can be high (i.e., 75-93%), as determined from measurements of maximal isometric torque produced by the anterior crural muscles. Isometric torque production is not adversely affected by the nerve cuff because the torque produced matches that observed in our established percutaneous stimulation model. We also demonstrate that use of the nerve cuff for stimulation is compatible with electromyographic measurements made on the tibialis anterior muscle, with no sign of stimulation artifact in the electromyographic signal.

Dissociation of force production from MHC and actin contents in muscles injured by eccentric contractions.

The primary purpose of this study was to determine the relationship between myosin heavy chain (MHC) and actin contents and maximum isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles following eccentric contraction-induced injury. Po and protein contents were measured in injured (n = 80) and contralateral control (n = 80) EDL muscles at the following time points after in vivo injury: sham, 0, 0.25, 1, 3, 5, 14, and 28 days. Po was reduced by 37 +/- 2.3% to 49 +/- 3.8% (p < or = 0.05), while MHC and actin contents were unaltered from 0 to 3 days after injury. Whereas Po partially recovered between 3 and 5 days (from -49 +/- 3.8% to -35 +/- 3.6%), MHC and actin contents in the injured muscles declined by 19 +/- 4.9% and 20 +/- 5.3%, respectively, by 5 days compared with control muscles. Decrements in Po were similar to the reductions in MHC and actin contents at 14 (approximately 24%) and 28 (approximately 11%) days. Evaluation of myofibrillar and soluble protein fractions indicated significant reductions in the content of major proteins at 5 and 14 days. Immunoblots of heat shock protein 72 revealed elevations starting at 0.25 days, peaking during 1-3 days, and declining after 5 days. These findings indicate that decreased contractile protein content is not related to the initial decrease in Po. However, decreased MHC and actin contents could account for 58% of the Po reduction at 5 days, and for nearly all the decrements in Po from 14 to 28 days.

Decreased contraction economy in mouse EDL muscle injured by eccentric contractions.

The objective of this study was to find out whether basal and/or active energy metabolism are altered in isolated mouse extensor digitorum longus muscle injured by eccentric (Ecc) contractions. Measurements of basal O2 consumption and isometric tetanus O2 recovery cost were made at 25 degrees C on muscles that had done either 10 Ecc, 10 isometric (Iso), or no contractions (No). In parallel experiments, rates of lactate and pyruvate production were measured to estimate the anaerobic contribution. Basal O2 consumption was unaffected by the type of protocol performed (P = 0.07). However, the tetanus O2 cost per force-time integral was elevated by 30-36% for the Ecc protocol muscles over that for the Iso and No protocol muscles. When including the increased lactate production by the Ecc protocol muscles, the total energetic cost per force-time integral was 53% higher than that for the Iso protocol muscles [2.35 +/- 0.17 vs. 1.54 +/- 0.18 mumol O2/(N.m.s)]. The decreased economy was attributed to two factors. First, in skinned fibers isolated from the injured muscles, the ratio of maximal actomyosin adenosinetriphosphatase activity to force production was up by 37.5%, suggesting uncoupling of ATP hydrolysis from force production. Second, increased reliance on anaerobic metabolism along with the fluorescent microscopic study of mitochondrial membrane potential and histochemical study of ATP synthase suggested an uncoupling of oxidative phosphorylation in the injured muscles.

Effects of concentric and eccentric training on muscle strength, cross-sectional area, and neural activation.

We compared the effects of concentric (Con) and eccentric (Ecc) isokinetic training on quadriceps muscle strength, cross-sectional area, and neural activation. Women (age 20.0 +/- 0.5 yr) randomly assigned to Con training (CTG; n = 16), Ecc training (ETG; n = 19), and control (CG; n = 19) groups were tested before and after 10 wk of unilateral Con or Ecc knee-extension training. Average torque measured during Con and Ecc maximal voluntary knee extensions increased 18.4 and 12.8% for CTG, 6.8 and 36.2% for ETG, and 4.7 and -1.7% for CG, respectively. Increases by CTG and ETG were greater than for CG (P < 0.05). For CTG, the increase was greater when measured with Con than with Ecc testing. For ETG, the increase was greater when measured with Ecc than with Con testing. The increase by ETG with Ecc testing was greater than the increase by CTG with Con testing. Corresponding changes in the integrated voltage from an electromyogram measured during strength testing were 21.7 and 20.0% for CTG, 7.1 and 16.7% for ETG, and -8.0 and -9.1% for CG. Quadriceps cross-sectional area measured by magnetic resonance imaging (sum of 7 slices) increased more in ETG (6.6%) than in CTG (5.0%) (P < 0.05). We conclude that Ecc is more effective than Con isokinetic training for developing strength in Ecc isokinetic muscle actions and that Con is more effective than Ecc isokinetic training for developing strength in Con isokinetic muscle actions. Gains in strength consequent to Con and Ecc training are highly dependent on the muscle action used for training and testing. Muscle hypertrophy and neural adaptations contribute to strength increases consequent to both Con and Ecc training.

Estradiol effect on anterior crural muscles-tibial bone relationship and susceptibility to injury.

The study's objective was to determine whether estradiol (E2) deficiency alters the functional relationship of muscle to bone and causes a differential increase in injury susceptibility. Ovariectomized 6-wk-old mice were administered E2 (40 micrograms. day-1. kg-1; n = 8) or the oil vehicle (n = 8) for 21 days. The anterior crural muscles of the left hindlimb were then stimulated to produce 150 maximal in vivo eccentric contractions. In vitro functional measurements were then made on the extensor digitorum longus (EDL) muscle and tibia from both the exercised and unexercised legs. The maximal isometric torque produced by the anterior crural muscles before the eccentric contraction protocol and the unexercised EDL maximal isometric tetanic force (P(0)) were higher in E2-treated mice by 18 and 14%, respectively (P < or = 0.03). Both ultimate load and stiffness for the unexercised tibia were higher by 16% in E2-treated mice (P < or = 0.03). The muscle-to-bone relationship of these measurements was unaffected by E2 status (P > or = 0.59). No evidence for increased injury susceptibility was found in either tissue from E2-deficient mice. In fact, the decrement in P(0) was only 36.9 +/- 3.8% in exercised EDL muscles from E2-deficient mice compared with 50.6 +/- 4.2% in exercised muscles from E2-treated mice (P = 0.03). Tibia stiffness was 3.9% higher in bones from exercised legs than in bones from unexercised legs (72.64 +/- 2.77 vs. 69.95 +/- 2.66 N/mm; P = 0.05) with ultimate load showing a similar trend (P = 0.07); no effect of E2 status was observed on these differences (P > or = 0.53). In conclusion, the functional relationship of bone to muscle and the susceptibility to injury in bone are not altered by the presence of E2 in ovariectomized mice; however, E2 does increase injury susceptibility in the EDL muscle.