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

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 < 0.001). 20E supplementation completely recovered muscle function after 7 days in both adult and old mice (pre vs. 7-day; p > 0.05), while PLA muscle function remained reduced (pre vs. 7-day; p < 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.

1996 ◽  
Vol 80 (1) ◽  
pp. 332-340 ◽  
Author(s):  
C. P. Ingalls ◽  
G. L. Warren ◽  
D. A. Lowe ◽  
D. B. Boorstein ◽  
R. B. Armstrong

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.


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

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
David Hydock ◽  
Asma Omar ◽  
Eric Bredahl ◽  
Colin Quinn

2021 ◽  
Vol 12 ◽  
Author(s):  
Mario Elkes ◽  
Martin Andonovski ◽  
Daislyn Vidal ◽  
Madison Farago ◽  
Ryan Modafferi ◽  
...  

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.


2020 ◽  
Vol 61 (3) ◽  
pp. 416-424
Author(s):  
Charlotte Gineste ◽  
Augustin C. Ogier ◽  
Isabelle Varlet ◽  
Zaynab Hourani ◽  
Monique Bernard ◽  
...  

2005 ◽  
Vol 30 (5) ◽  
pp. 576-590 ◽  
Author(s):  
David J. Baker ◽  
Russell T. Hepple

The pump-perfused rat hindlimb model, in various forms, has been in use for several decades. There are many applications for this model, owing to the ability to control the content and rate of perfusion. In the context of exercise physiology this model has been put to particularly good use. In this report we summarize some of the central surgical differences between different versions of the pump-perfused rat hindlimb model, including the double hindlimb + trunk, double hindlimb alone, single hindlimb, and distal hindlimb-alone models. We also summarize specific elements of the perfusion medium and measurement of force used in our lab during assessment of muscle metabolic and contractile responses, and illustrate some of the differences from the in vivo condition that merit consideration. We then provide specific examples of how the single pump-perfused hindlimb and distal hindlimb-alone versions of this model have been used to study muscle function and energy metabolism. In this context we show how this model can be used to permit the experimenter to manipulate and control the rate of O2delivery and to add specific compounds that inhibit a particular aspect of muscle metabolism, such that in combination with measurements of the flux of specific substances across the muscle and/or fast-freezing of muscle after contractions, more can be understood about the metabolic state of the contracting muscles. Key words: aerobic metabolism, mitochondria, aging, adaptation


1991 ◽  
Vol 261 (4) ◽  
pp. H1178-H1183
Author(s):  
E. O. Weselcouch ◽  
R. I. Grove ◽  
C. D. Demusz ◽  
A. J. Baird

Neutrophils are reported to play an important role in the genesis of tissue damage during reperfusion after periods of ischemia in a variety of organs and may also be involved in loss of tissue function during ischemia. To test this hypothesis, the monoclonal antibody, MoAb 60.3, which prevents the adhesion of ferret neutrophils to cultured human endothelial cells at a concentration of 30 micrograms/ml, was tested in a model of peripheral vascular disease to determine whether it would preserve skeletal muscle function during ischemia. In an anesthetized ferret the muscles of the hindlimb were stimulated electrically to contract isometrically and the force of contraction was measured. Under normal perfusion conditions the contractile force peaked within 1 or 2 min of initiation of stimulation and gradually declined to approximately 80% of peak force after 20 min. When femoral arterial pressure was reduced to 45 mmHg by partial occlusion of the abdominal aorta, peak force was reduced by 25 +/- 7%, and within 5 min the force decayed to approximately 20% of the original peak, resulting in an area under the force-time curve (AUC) of 32 +/- 5% of that seen during the normal flow period. During ischemia after treatment with MoAb 60.3 (2 mg/kg iv), peak force was 94 +/- 3% and AUC was 49 +/- 5% of that observed during the normal flow period, a significant protective effect compared with the untreated control group (P = 0.0294). When the nonneutrophil-directed monoclonal antibody, L6, was tested in this model, no protective effects were evident.(ABSTRACT TRUNCATED AT 250 WORDS)


1995 ◽  
Vol 79 (4) ◽  
pp. 1260-1270 ◽  
Author(s):  
D. A. Lowe ◽  
G. L. Warren ◽  
C. P. Ingalls ◽  
D. B. Boorstein ◽  
R. B. Armstrong

This study was designed to determine the relationship between skeletal muscle function and protein metabolism after initiation of eccentric contraction-induced injury. Mouse anterior crural muscles were injured in vivo, and then either immediately or 3, 6, 24, 48, 72, 120, or 336 h after injury muscles were isolated and studied for indexes of muscle function, injury, phagocyte infiltration, and protein metabolism. A group of mice were administered anti-polymorphonuclear cell and anti-macrophage antisera in an attempt to reduce phagocytic infiltration into injured muscle. Force production in extensor digitorum longus muscles was reduced 55% immediately after injury induction and did not recover significantly until 120 h postinjury (28% below baseline). However, rates of protein degradation were not elevated until 48 h postinjury (60% above normal) and were not correlated with the changes in force production (r = -0.37; P = 0.24). Phagocytic infiltration was evident 24–120 h postinjury and was correlated with the elevated protein degradation rates (r = 0.75; P < 0.01). Protein synthesis rates began to increase approximately 48 h after injury was induced and were elevated by 83% 5 days postinjury. Fourteen days after injury, muscle protein degradation and synthesis rates had returned to normal, as well as specific force production, and phagocytic infiltration was not detected. However, muscle mass, protein content, and absolute force production were lower than normal. Antisera-treated mice were rendered neutropenic, but there was no difference in any variable measured between muscles from these mice and muscles from normal mice.


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