Differential effects of anesthetics on in vivo skeletal muscle contractile function in the mouse

1996 ◽  
Vol 80 (1) ◽  
pp. 332-340 ◽  
Author(s):  
C. P. Ingalls ◽  
G. L. Warren ◽  
D. A. Lowe ◽  
D. B. Boorstein ◽  
R. B. Armstrong
Keyword(s):  
Skeletal Muscle ◽  
Contractile Function ◽  
Average Power ◽  
Eccentric Contraction ◽  
Peak Torque ◽  
High Dose ◽  
Skeletal Muscle Function ◽  
Contractile Responses ◽  
Time Integral

The purpose of this study was to evaluate the effects of four anesthetic regimens on in vivo contractile function of mouse ankle dorsiflexor muscles. The torque-frequency and torque-velocity relationships were determined for the following anesthetics: fentanyl-droperidol and diazepam (F-d/d); ketamine and xylazine (K/x); pentobarbital sodium (Ps); and methoxyflurane (Mf). Mf, Ps, and F-d/d regimens resulted in comparable contractile responses at low doses, whereas K/x produced a relative depression in isometric contractile function as shown by a decrease in the torque-time integral at the 300-Hz stimulation frequency (-13.9%; P < 0.05). Moreover, K/x caused a shift to the left in the torque-frequency curve as indicated by increases in torque-time integrals at 25 and 50 Hz. Both Ps and F-d/d regimens exhibited dose-dependent effects during the isovelocity contractions. Ps significantly reduced work (-28.7%) and average power (-28.9%) at 800 degrees/s at the high dose. In contrast, F-d/d anesthesia resulted in increases in peak torque (16-20%) and work (15-18%) output at all eccentric contraction velocities at the high dose, whereas average power was increased only at -800 (17%) and -1,000 degrees/s (17%). In conclusion, commonly used anesthetic regimens can affect the contractile response in vivo; K/x and Ps yield smaller torque outputs, whereas Mf and F-d/d consistently produce larger contractile responses. Mf and F-d/d are recommended for use in studying skeletal muscle function in mice in vivo.

scholarly journals Phytoecdysteroids Accelerate Recovery of Skeletal Muscle Function Following in vivo Eccentric Contraction-Induced Injury in Adult and Old Mice

2021 ◽  
Vol 2 ◽  
Author(s):  
Kevin A. Zwetsloot ◽  
R. Andrew Shanely ◽  
Joshua S. Godwin ◽  
Charles F. Hodgman
Keyword(s):  
Skeletal Muscle ◽  
Muscle Damage ◽  
Muscle Function ◽  
Recovery Period ◽  
Eccentric Contraction ◽  
Eccentric Contractions ◽  
Post Injury ◽  
Skeletal Muscle Function ◽  
Old Mice

Background: Eccentric muscle contractions are commonly used in exercise regimens, as well as in rehabilitation as a treatment against muscle atrophy and weakness. If repeated multiple times, eccentric contractions may result in skeletal muscle injury and loss of function. Skeletal muscle possesses the remarkable ability to repair and regenerate after an injury or damage; however, this ability is impaired with aging. Phytoecdysteroids are natural plant steroids that possess medicinal, pharmacological, and biological properties, with no adverse side effects in mammals. Previous research has demonstrated that administration of phytoecdysteroids, such as 20-hydroxyecdysone (20E), leads to an increase in protein synthesis signaling and skeletal muscle strength.Methods: To investigate whether 20E enhances skeletal muscle recovery from eccentric contraction-induced damage, adult (7–8 mo) and old (26–27 mo) mice were subjected to injurious eccentric contractions (EC), followed by 20E or placebo (PLA) supplementation for 7 days. Contractile function via torque-frequency relationships (TF) was measured three times in each mouse: pre- and post-EC, as well as after the 7-day recovery period. Mice were anesthetized with isoflurane and then electrically-stimulated isometric contractions were performed to obtain in vivo muscle function of the anterior crural muscle group before injury (pre), followed by 150 EC, and then again post-injury (post). Following recovery from anesthesia, mice received either 20E (50 mg•kg−1 BW) or PLA by oral gavage. Mice were gavaged daily for 6 days and on day 7, the TF relationship was reassessed (7-day).Results: EC resulted in significant reductions of muscle function post-injury, regardless of age or treatment condition (p &lt; 0.001). 20E supplementation completely recovered muscle function after 7 days in both adult and old mice (pre vs. 7-day; p &gt; 0.05), while PLA muscle function remained reduced (pre vs. 7-day; p &lt; 0.01). In addition, histological markers of muscle damage appear lower in damaged muscle from 20E-treated mice after the 7-day recovery period, compared to PLA.Conclusions: Taken together, these findings demonstrate that 20E fully recovers skeletal muscle function in both adult and old mice just 7 days after eccentric contraction-induced damage. However, the underlying mechanics by which 20E contributes to the accelerated recovery from muscle damage warrant further investigation.

scholarly journals Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle

2006 ◽  
Vol 173 (6) ◽  
pp. 905-916 ◽  
Author(s):  
Marie-Louise Bang ◽  
Xiaodong Li ◽  
Ryan Littlefield ◽  
Shannon Bremner ◽  
Andrea Thor ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thin Filament ◽  
Contractile Function ◽  
Critical Role ◽  
Force Production ◽  
Skeletal Muscle Function ◽  
Sarcomeric Protein ◽  
Ultrastructural Studies ◽  
Deficient Mice

Nebulin is a giant modular sarcomeric protein that has been proposed to play critical roles in myofibrillogenesis, thin filament length regulation, and muscle contraction. To investigate the functional role of nebulin in vivo, we generated nebulin-deficient mice by using a Cre knock-in strategy. Lineage studies utilizing this mouse model demonstrated that nebulin is expressed uniformly in all skeletal muscles. Nebulin-deficient mice die within 8–11 d after birth, with symptoms including decreased milk intake and muscle weakness. Although myofibrillogenesis had occurred, skeletal muscle thin filament lengths were up to 25% shorter compared with wild type, and thin filaments were uniform in length both within and between muscle types. Ultrastructural studies also demonstrated a critical role for nebulin in the maintenance of sarcomeric structure in skeletal muscle. The functional importance of nebulin in skeletal muscle function was revealed by isometric contractility assays, which demonstrated a dramatic reduction in force production in nebulin-deficient skeletal muscle.

Effects of In Vivo Doxorubicin Treatment on Skeletal Muscle Function

2011 ◽  
Vol 43 (Suppl 1) ◽  
pp. 903
Author(s):  
David S. Hydock ◽  
Chia-Ying Lien ◽  
Brock T. Jensen ◽  
Traci L. Parry ◽  
Carole M. Schneider ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Skeletal Muscle Function ◽  
Doxorubicin Treatment

scholarly journals Gene expression changes controlling distinct adaptations in the heart and skeletal muscle of a hibernating mammal

2015 ◽  
Vol 47 (3) ◽  
pp. 58-74 ◽  
Author(s):  
Katie L. Vermillion ◽  
Kyle J. Anderson ◽  
Marshall Hampton ◽  
Matthew T. Andrews
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cardiac Tissue ◽  
Contractile Function ◽  
Oxygen Demand ◽  
Oxidative Capacity ◽  
Disuse Atrophy ◽  
Functional Requirements ◽  
Skeletal Muscle Function ◽  
Illumina Hiseq

Throughout the hibernation season, the thirteen-lined ground squirrel ( Ictidomys tridecemlineatus) experiences extreme fluctuations in heart rate, metabolism, oxygen consumption, and body temperature, along with prolonged fasting and immobility. These conditions necessitate different functional requirements for the heart, which maintains contractile function throughout hibernation, and the skeletal muscle, which remains largely inactive. The adaptations used to maintain these contractile organs under such variable conditions serves as a natural model to study a variety of medically relevant conditions including heart failure and disuse atrophy. To better understand how two different muscle tissues maintain function throughout the extreme fluctuations of hibernation we performed Illumina HiSeq 2000 sequencing of cDNAs to compare the transcriptome of heart and skeletal muscle across the circannual cycle. This analysis resulted in the identification of 1,076 and 1,466 differentially expressed genes in heart and skeletal muscle, respectively. In both heart and skeletal muscle we identified a distinct cold-tolerant mechanism utilizing peroxisomal metabolism to make use of elevated levels of unsaturated depot fats. The skeletal muscle transcriptome also shows an early increase in oxidative capacity necessary for the altered fuel utilization and increased oxygen demand of shivering. Expression of the fetal gene expression profile is used to maintain cardiac tissue, either through increasing myocyte size or proliferation of resident cardiomyocytes, while skeletal muscle function and mass are protected through transcriptional regulation of pathways involved in protein turnover. This study provides insight into how two functionally distinct muscles maintain function under the extreme conditions of mammalian hibernation.

scholarly journals Physiological and histological changes in skeletal muscle following in vivo gene transfer by electroporation

2011 ◽  
Vol 301 (5) ◽  
pp. C1239-C1250 ◽  
Author(s):  
Joseph A. Roche ◽  
Diana L. Ford-Speelman ◽  
Lisa W. Ru ◽  
Allison L. Densmore ◽  
Renuka Roche ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Green Fluorescent Protein ◽  
Intramuscular Injection ◽  
Fluorescent Protein ◽  
Contractile Function ◽  
Complete Recovery ◽  
Secondary Damage ◽  
The Individual ◽  
Green Fluorescent

Electroporation (EP) is used to transfect skeletal muscle fibers in vivo, but its effects on the structure and function of skeletal muscle tissue have not yet been documented in detail. We studied the changes in contractile function and histology after EP and the influence of the individual steps involved to determine the mechanism of recovery, the extent of myofiber damage, and the efficiency of expression of a green fluorescent protein (GFP) transgene in the tibialis anterior (TA) muscle of adult male C57Bl/6J mice. Immediately after EP, contractile torque decreased by ∼80% from pre-EP levels. Within 3 h, torque recovered to ∼50% but stayed low until day 3. Functional recovery progressed slowly and was complete at day 28. In muscles that were depleted of satellite cells by X-irradiation, torque remained low after day 3, suggesting that myogenesis is necessary for complete recovery. In unirradiated muscle, myogenic activity after EP was confirmed by an increase in fibers with central nuclei or developmental myosin. Damage after EP was confirmed by the presence of necrotic myofibers infiltrated by CD68+ macrophages, which persisted in electroporated muscle for 42 days. Expression of GFP was detected at day 3 after EP and peaked on day 7, with ∼25% of fibers transfected. The number of fibers expressing green fluorescent protein (GFP), the distribution of GFP+ fibers, and the intensity of fluorescence in GFP+ fibers were highly variable. After intramuscular injection alone, or application of the electroporating current without injection, torque decreased by ∼20% and ∼70%, respectively, but secondary damage at D3 and later was minimal. We conclude that EP of murine TA muscles produces variable and modest levels of transgene expression, causes myofiber damage due to the interaction of intramuscular injection with the permeabilizing current, and that full recovery requires myogenesis.

scholarly journals Syncoilin is required for generating maximum isometric stress in skeletal muscle but dispensable for muscle cytoarchitecture

2008 ◽  
Vol 294 (5) ◽  
pp. C1175-C1182 ◽  
Author(s):  
Jianlin Zhang ◽  
Marie-Louise Bang ◽  
David S. Gokhin ◽  
Yingchun Lu ◽  
Li Cui ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Striated Muscle ◽  
Neuromuscular Diseases ◽  
Eccentric Contraction ◽  
Lateral Force ◽  
Force Transmission ◽  
Skeletal Muscle Contraction ◽  
Supportive Role

Syncoilin is a striated muscle-specific intermediate filament-like protein, which is part of the dystrophin-associated protein complex (DPC) at the sarcolemma and provides a link between the extracellular matrix and the cytoskeleton through its interaction with α-dystrobrevin and desmin. Its upregulation in various neuromuscular diseases suggests that syncoilin may play a role in human myopathies. To study the functional role of syncoilin in cardiac and skeletal muscle in vivo, we generated syncoilin-deficient ( syncoilin−/−) mice. Our detailed analysis of these mice up to 2 yr of age revealed that syncoilin is entirely dispensable for cardiac and skeletal muscle development and maintenance of cellular structure but is required for efficient lateral force transmission during skeletal muscle contraction. Notably, syncoilin−/− skeletal muscle generates less maximal isometric stress than wild-type (WT) muscle but is as equally susceptible to eccentric contraction-induced injury as WT muscle. This suggests that syncoilin may play a supportive role for desmin in the efficient coupling of mechanical stress between the myofibril and fiber exterior. It is possible that the reduction in isometric stress production may predispose the syncoilin skeletal muscle to a dystrophic condition.

scholarly journals In vivo Skeletal Muscle Function and Doxorubicin Treatment in the Rat

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
David Hydock ◽  
Asma Omar ◽  
Eric Bredahl ◽  
Colin Quinn
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Skeletal Muscle Function ◽  
Doxorubicin Treatment

scholarly journals The Influence of Supplemental Dietary Linoleic Acid on Skeletal Muscle Contractile Function in a Rodent Model of Barth Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Mario Elkes ◽  
Martin Andonovski ◽  
Daislyn Vidal ◽  
Madison Farago ◽  
Ryan Modafferi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Linoleic Acid ◽  
Muscle Function ◽  
Barth Syndrome ◽  
Dietary Linoleic Acid ◽  
Skeletal Muscle Function ◽  
Contractile Phenotype ◽  
Muscle Contractile

Barth syndrome is a rare and incurable X-linked (male-specific) genetic disease that affects the protein tafazzin (Taz). Taz is an important enzyme responsible for synthesizing biologically relevant cardiolipin (for heart and skeletal muscle, cardiolipin rich in linoleic acid), a critical phospholipid of mitochondrial form and function. Mutations to Taz cause dysfunctional mitochondria, resulting in exercise intolerance due to skeletal muscle weakness. To date, there has been limited research on improving skeletal muscle function, with interventions focused on endurance and resistance exercise. Previous cell culture research has shown therapeutic potential for the addition of exogenous linoleic acid in improving Taz-deficient mitochondrial function but has not been examined in vivo. The purpose of this study was to examine the influence of supplemental dietary linoleic acid on skeletal muscle function in a rodent model of Barth syndrome, the inducible Taz knockdown (TazKD) mouse. One of the main findings was that TazKD soleus demonstrated an impaired contractile phenotype (slower force development and rates of relaxation) in vitro compared to their WT littermates. Interestingly, this impaired contractile phenotype seen in vitro did not translate to altered muscle function in vivo at the whole-body level. Also, supplemental linoleic acid attenuated, to some degree, in vitro impaired contractile phenotype in TazKD soleus, and these findings appear to be partially mediated by improvements in cardiolipin content and resulting mitochondrial supercomplex formation. Future research will further examine alternative mechanisms of dietary supplemental LA on improving skeletal muscle contractile dysfunction in TazKD mice.

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