Biomedical subjects

R B Armstrong

Publications and source records attributed to R B Armstrong.

At least 19 recordsLinked to original sources

PubMed2004

Adaptation to lengthening contraction-induced injury in mouse muscle.

Adaptations to repeated bouts of injury-inducing lengthening contractions were studied in mouse anterior crural muscles. Five bouts of 150 lengthening contractions were performed in vivo, with each bout separated by 2 wk of rest. Three primary observations were made. First, there was little, if any, attenuation in the immediate isometric torque losses after lengthening contractions at "physiological" stimulation frequencies (i.e., <125 Hz), although there was a pronounced decrease in torque loss at higher frequencies between the first and second bouts. Second, the immediate losses in strength that occurred after all five lengthening contraction bouts could be explained in part by excitation-contraction uncoupling. Third, the most important adaptation was a significant enhancement in the rate of recovery of strength after the lengthening contractions. It is probable that the accelerated rate of strength recovery resulted from the more rapid loss and subsequent recovery of myofibrillar protein observed after the fifth bout.

Adaptation, Physiological↗

PubMed2003

Dihydropyridine and ryanodine receptor binding after eccentric contractions in mouse skeletal muscle.

The purpose of this study was to determine whether there are alterations in the dihydropyridine and/or ryanodine receptors that might explain the excitation-contraction uncoupling associated with eccentric contraction-induced skeletal muscle injury. The left anterior crural muscles (i.e., tibialis anterior, extensor digitorum longus, and extensor hallucis longus) of mice were injured in vivo by 150 eccentric contractions. Peak isometric tetanic torque of the anterior crural muscles was reduced approximately 45% immediately and 3 days after the eccentric contractions. Partial restoration of peak isometric tetanic and subtetanic forces of injured extensor digitorum longus muscles by 10 mM caffeine indicated the presence of excitation-contraction uncoupling. Scatchard analysis of [3H]ryanodine binding indicated that the number of ryanodine receptor binding sites was not altered immediately postinjury but decreased 16% 3 days later. Dihydropyridine receptor binding sites increased approximately 20% immediately after and were elevated to the same extent 3 days after the injury protocol. Muscle injury did not alter the sensitivity of either receptor. These data suggest that a loss or altered sensitivity of the dihydropyridine and ryanodine receptors does not contribute to the excitation-contraction uncoupling immediately after contraction-induced muscle injury. We also concluded that the loss in ryanodine receptors 3 days after injury is not the primary cause of excitation-contraction uncoupling at that time.

Animals↗

PubMed2003

Importance of satellite cells in the strength recovery after eccentric contraction-induced muscle injury.

The purpose of this study was to determine if the elimination of satellite cell proliferation using gamma-irradiation would inhibit normal force recovery after eccentric contraction-induced muscle injury. Adult female ICR mice were implanted with a stimulating nerve cuff on the common peroneal nerve and assigned to one of four groups: 1) irradiation- and eccentric contraction-induced injury, 2) eccentric contraction-induced injury only, 3) irradiation only, and 4) no intervention. Anterior crural muscles were irradiated with a dose of 2,500 rad and injured with 150 in vivo maximal eccentric contractions. Maximal isometric torque was determined weekly through 35 days postinjury. Immediately after injury, maximal isometric torque was reduced by approximately 50% and had returned to normal by 28 days postinjury in the nonirradiated injured mice. However, torque production of irradiated injured animals did not recover fully and was 25% less than that of injured nonirradiated mice 35 days postinjury. These data suggest that satellite cell proliferation is required for approximately half of the force recovery after eccentric contraction-induced injury.

Animals↗

PubMed2003

Mechanisms of force loss in diabetic mouse skeletal muscle.

Pathologic changes to alpha-motoneurons may contribute to decreases in skeletal muscle strength in diabetes. The present study examines this possibility. Female ICR mice (approximately 25 g) were given a single injection of streptozotocin (200 mg/kg). After 2, 4, and 8 weeks of diabetes, we measured maximum isometric tetanic torque of the fast-twitch anterior crural muscles at the ankle when stimulated through the common peroneal nerve, and maximal isometric tetanic force in the directly stimulated extensor digitorum longus (EDL) muscle. After 4 weeks, the relative loss of torque via nerve stimulation (-43%) was greater (P = 0.02) than the force loss in the directly stimulated muscle (-24%), indicating a functional neural deficit. However, the percent changes in strength in these two methods of stimulation were not different (P = 0.41) in the 8-week diabetic animals, indicating that functional impairment resided in the muscle. This suggests an early distal motoneuron or neuromuscular junction deficit that improved as the intrinsic muscle deficit worsened. Preliminary evidence also suggests excitation-contraction uncoupling may contribute to the loss of strength in fast-twitch muscles.

Animals↗

PubMed2002

Temperature dependency of force loss and Ca(2+) homeostasis in mouse EDL muscle after eccentric contractions.

The goals of this study were first to determine the effect of temperature on the force loss that results from eccentric contractions in mouse extensor digitorum longus (EDL) muscles and then to evaluate a potential role for altered Ca(2+) homeostasis explaining the greater isometric force loss observed at the higher temperatures. Isolated muscles performed five eccentric or five isometric contractions at either 15, 20, 25, 30, 33.5, or 37 degrees C. Isometric force loss, caffeine-induced force, lactate dehydrogenase (LDH) release, muscle accumulation of (45)Ca(2+) from the bathing medium, sarcoplasmic reticulum (SR) Ca(2+) uptake, and resting muscle fiber free cytosolic Ca(2+) concentration ([Ca(2+)](i)) were measured. The isometric force loss after eccentric contractions increased progressively as temperature rose; at 15 degrees C, there was no significant loss of force, but at 37 degrees C, there was a 30-39% loss of force. After eccentric contractions, caffeine-induced force was not affected by temperature nor was it different from that of control muscles at any temperature. Loss of cell membrane integrity and subsequent influx of extracellular Ca(2+) as indicated by LDH release and muscle (45)Ca(2+) accumulation, respectively, were minimal over the 15-25 degrees C range, but both increased as an exponential function of temperature between 30 and 37 degrees C. SR Ca(2+) uptake showed no impairment as temperature increased, and the eccentric contraction-induced rise in resting fiber [Ca(2+)](i) was unaffected by temperature over the 15-25 degrees C range. In conclusion, the isometric force loss after eccentric contractions is temperature dependent, but the temperature dependency does not appear to be readily explainable by alterations in Ca(2+) homeostasis.

Animals↗

PubMed2002

What mechanisms contribute to the strength loss that occurs during and in the recovery from skeletal muscle injury?

In the workplace or on the athletic field, muscle strength can be decreased by 50% or more following performance of a relatively few high-force, eccentric contractions. The strength loss can be prolonged, taking a month or more for complete recovery. It is important to understand the cause(s) of the strength loss so we can develop means of preventing or attenuating this loss. The cellular-level mechanisms explaining the loss of strength following contraction-induced muscle injury remain controversial. The traditional thought is that initial strength loss is due solely to damage to force-bearing structures within the muscle, as evidenced by histopathology. In addition, inflammation in the days following injury is commonly thought to exacerbate the strength loss. We present data to the contrary. Recent data show that most of the early strength loss results from a failure of excitation-contraction coupling processes and that a slow loss of contractile protein in the days following injury prolongs the time for recovery.

Humans↗

PubMed2001

Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine.

1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

Animals↗

PubMed2001

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.

Animals↗

PubMed2001

Time course changes in [Ca2+]i, force, and protein content in hindlimb-suspended mouse soleus muscles.

BACKGROUND: Exposure to reduced gravitational forces during spaceflight is associated with significant reductions in skeletal muscle mass and strength. The purpose of this study was to test the hypothesis that increases in resting cytosolic free calcium concentration ([Ca2+]i) would precede reductions in protein content and maximal isometric tetanic force (Po) in mouse soleus muscle after initiation of hindlimb suspension. METHODS: Female ICR mice (n = 42) were hindlimb suspended for 1, 2, 3, 5, or 7 d; weight-matched mice were used as controls. Following the hindlimb suspension, the left soleus muscle was used to determine Po in vitro and the right soleus muscle was used to determine protein content and [Ca2+]i via confocal laser scanning microscopy. RESULTS: Compared with controls, [Ca2+]i was elevated by 38% at 2 d, and 117% at 7 d. Compared with controls, soleus muscle total and myofibrillar protein contents were reduced 27-29% and 30-34%, respectively, at 5-7 d after initiation of hindlimb suspension. Compared with controls, soleus muscle Po was decreased by 24% at 3 d, and 38% at 7 d. CONCLUSION: It appears that resting cytosolic Ca2+ homeostasis is disturbed soon after the initiation of hindlimb suspension, and these elevations in [Ca2+]i may play a role in initiating soleus muscle atrophy.

Analysis of Variance↗

PubMed2000

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.

Adult↗

PubMed1999

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.

Animals↗

PubMed1999

Rat hindlimb muscle blood flow during level and downhill locomotion.

During eccentrically biased exercise (e.g., downhill locomotion), whole body oxygen consumption and blood lactate concentrations are lower than during level locomotion. These general systemic measurements indicate that muscle metabolism is lower during downhill exercise. This study was designed to test the hypothesis that hindlimb muscle blood flow is correspondingly lower during downhill vs. level exercise. Muscle blood flow (determined by using radioactive microspheres) was measured in rats after 15 min of treadmill exercise at 15 m/min on the level (L, 0 degrees) or downhill (D, -17 degrees). Blood flow to ankle extensor muscles was either lower (e.g., white gastrocnemius muscle: D, 9 +/- 2; L, 15 +/- 1 ml. min-1. 100 g-1) or not different (e.g., soleus muscle: D, 250 +/- 35; L, 230 +/- 21 ml. min-1. 100 g-1) in downhill vs. level exercise. In contrast, blood flow to ankle flexor muscles was higher (e.g., extensor digitorum longus muscle: D, 53 +/- 5; L, 31 +/- 6 ml. min-1. 100 g-1) during downhill vs. level exercise. When individual extensor and flexor muscle flows were summed, total flow to the leg was lower during downhill exercise (D, 3.24 +/- 0.08; L, 3.47 +/- 0. 05 ml/min). These data indicate that muscle blood flow and metabolism are lower during eccentrically biased exercise but are not uniformly reduced in all active muscles; i.e., flows are equivalent in several ankle extensor muscles and higher in ankle flexor muscles.

Animals↗

PubMed1999

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).

Animals↗

PubMed1999

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.

Animals↗

PubMed1999

Effects of acitretin on the liver.

BACKGROUND: Therapy with aromatic retinoids for psoriasis is associated with abnormal liver function test findings and toxic hepatitis (in 1.5% of patients). OBJECTIVE: Our purpose was to determine the safety of acitretin with respect to liver function, on the basis of biopsy. METHODS: We treated 128 adults (with chronic, stable psoriasis) with oral acitretin (25-75 mg/day) for four 6-month intervals in a prospective, open-label, 2-year multicenter study. Liver biopsies were performed before and after study completion (2 years). RESULTS: Eighty-three available pairs of pretreatment and posttreatment liver biopsies demonstrated no change in 49 patients (59%), improvement in 20 (24%), and worsening in 14 (17%). Of these 14 patients with decrements in biopsy status, most changes were mild. There was no correlation between liver function test abnormalities or cumulative acitretin dose and changes in liver biopsy status. CONCLUSION: Acitretin therapy elicited no biopsy-proven hepatotoxicity in this prospective 2-year study. These findings suggest that periodic liver biopsy may not be necessary with acitretin treatment.

Acitretin↗

PubMed1998

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.

Actins↗

PubMed1998

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.

Animals↗

PubMed1998

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.

Animals↗