Early functional muscle regeneration after myotoxic injury in mice is unaffected by nNOS absence

2011 ◽  
Vol 301 (5) ◽  
pp. R1358-R1366 ◽  
Author(s):  
Jarrod E. Church ◽  
Stefan M. Gehrig ◽  
Annabel Chee ◽  
Timur Naim ◽  
Jennifer Trieu ◽  
...  

Nitric oxide (NO) is an important signaling molecule produced in skeletal muscle primarily via the neuronal subtype of NO synthase (NOS1, or nNOS). While many studies have reported NO production to be important in muscle regeneration, none have examined the contribution of nNOS-derived NO to functional muscle regeneration (i.e., restoration of the muscle's ability to produce force) after acute myotoxic injury. In the present study, we tested the hypothesis that genetic deletion of nNOS would impair functional muscle regeneration after myotoxic injury in nNOS−/− mice. We found that nNOS−/− mice had lower body mass, lower muscle mass, and smaller myofiber cross-sectional area and that their tibialis anterior (TA) muscles produced lower absolute tetanic forces than those of wild-type littermate controls but that normalized or specific force was identical between the strains. In addition, muscles from nNOS−/− mice were more resistant to fatigue than those of wild-type littermates ( P < 0.05). To determine whether deletion of nNOS affected muscle regeneration, TA muscles from nNOS−/− mice and wild-type littermates were injected with the myotoxin notexin to cause complete fiber degeneration, and muscle structure and function were assessed at 7 and 10 days postinjury. Myofiber cross-sectional area was lower in regenerating nNOS−/− mice than wild-type controls at 7 and 10 days postinjury; however, contrary to our original hypothesis, no difference in force-producing capacity of the TA muscle was evident between the two groups at either time point. Our findings reveal that nNOS is not essential for functional muscle regeneration after acute myotoxic damage.

Hand ◽  
2021 ◽  
pp. 155894472199973
Author(s):  
Shruthi Deivasigamani ◽  
Ali Azad ◽  
S. Steven Yang

Background The abductor pollicis longus (APL) is classically described as inserting on the base of the first metacarpal. This study analyzed APL insertional anatomy and quantified the size of various elements of the extensor side of the thumb to determine associations with size and function. Methods Twenty-four formalin-preserved upper limbs were dissected. The insertional anatomy of the APL, extensor pollicis brevis, and extensor pollicis longus were characterized, and the capacity of APL tendon slips to perform palmar abduction of the first digit was quantified based on slip size and insertion. Results The mean number of APL tendon slips observed was 2.3. Abductor pollicis longus insertion sites included the base of the first metacarpal, trapezium, abductor pollicis brevis, and opponens pollicis. Only 4 specimens had a solitary metacarpal slip, while 83% of specimens had insertions onto at least 1 thenar muscle. A total of 62.5% of APL tendons exhibited some form of branching that we categorized into “Y” and “Z” patterns. In assessing palmar abduction capacity, we found that APL tendon slips inserting into the base of the first metacarpal were larger in cross-sectional area than nonmetacarpal slips and reproduced complete palmar abduction of the digit in the absence of nonmetacarpal slips. The abduction capacity of APL tendon slips was not correlated to the cross-sectional area. Conclusions There is significant variability in APL tendon slips, branching patterns, and insertional anatomy. These findings provide further understanding of the function of the APL and its surgical implications.


2016 ◽  
Vol 52 (1) ◽  
pp. 12-23 ◽  
Author(s):  
Ran S Sopher ◽  
Andrew A Amis ◽  
D Ceri Davies ◽  
Jonathan RT Jeffers

Data about a muscle’s fibre pennation angle and physiological cross-sectional area are used in musculoskeletal modelling to estimate muscle forces, which are used to calculate joint contact forces. For the leg, muscle architecture data are derived from studies that measured pennation angle at the muscle surface, but not deep within it. Musculoskeletal models developed to estimate joint contact loads have usually been based on the mean values of pennation angle and physiological cross-sectional area. Therefore, the first aim of this study was to investigate differences between superficial and deep pennation angles within each muscle acting over the ankle and predict how differences may influence muscle forces calculated in musculoskeletal modelling. The second aim was to investigate how inter-subject variability in physiological cross-sectional area and pennation angle affects calculated ankle contact forces. Eight cadaveric legs were dissected to excise the muscles acting over the ankle. The mean surface and deep pennation angles, fibre length and physiological cross-sectional area were measured. Cluster analysis was applied to group the muscles according to their architectural characteristics. A previously validated OpenSim model was used to estimate ankle muscle forces and contact loads using architecture data from all eight limbs. The mean surface pennation angle for soleus was significantly greater (54%) than the mean deep pennation angle. Cluster analysis revealed three groups of muscles with similar architecture and function: deep plantarflexors and peroneals, superficial plantarflexors and dorsiflexors. Peak ankle contact force was predicted to occur before toe-off, with magnitude greater than five times bodyweight. Inter-specimen variability in contact force was smallest at peak force. These findings will help improve the development of experimental and computational musculoskeletal models by providing data to estimate force based on both surface and deep pennation angles. Inter-subject variability in muscle architecture affected ankle muscle and contact loads only slightly. The link between muscle architecture and function contributes to the understanding of the relationship between muscle structure and function.


2013 ◽  
Vol 115 (8) ◽  
pp. 1119-1125 ◽  
Author(s):  
Yuki Fujimoto ◽  
Jyongsu Huang ◽  
Toshiharu Fukunaga ◽  
Ryo Kato ◽  
Mari Higashino ◽  
...  

The acoustic reflection technique noninvasively measures airway cross-sectional area vs. distance functions and uses a wave tube with a constant cross-sectional area to separate incidental and reflected waves introduced into the mouth or nostril. The accuracy of estimated cross-sectional areas gets worse in the deeper distances due to the nature of marching algorithms, i.e., errors of the estimated areas in the closer distances accumulate to those in the further distances. Here we present a new technique of acoustic reflection from measuring transmitted acoustic waves in the airway with three microphones and without employing a wave tube. Using miniaturized microphones mounted on a catheter, we estimated reflection coefficients among the microphones and separated incidental and reflected waves. A model study showed that the estimated cross-sectional area vs. distance function was coincident with the conventional two-microphone method, and it did not change with altered cross-sectional areas at the microphone position, although the estimated cross-sectional areas are relative values to that at the microphone position. The pharyngeal cross-sectional areas including retropalatal and retroglossal regions and the closing site during sleep was visualized in patients with obstructive sleep apnea. The method can be applicable to larger or smaller bronchi to evaluate the airspace and function in these localized airways.


2002 ◽  
Vol 282 (5) ◽  
pp. H1697-H1702 ◽  
Author(s):  
Hui Di Wang ◽  
Douglas G. Johns ◽  
Shanqin Xu ◽  
Richard A. Cohen

Our purpose was to address the role of NAPDH oxidase-derived superoxide anion in the vascular response to ANG II. Blood pressure, aortic superoxide anion, 3-nitrotyrosine, and medial cross-sectional area were compared in wild-type mice and in mice that overexpress human superoxide dismutase (hSOD). The pressor response to ANG II was significantly less in hSOD mice. Superoxide anion levels were increased twofold in ANG II-treated wild-type mice but not in hSOD mice. 3-Nitrotyrosine increased in aortic endothelium and adventitia in wild-type but not hSOD mice. In contrast, aortic medial cross-sectional area increased 50% with ANG II in hSOD mice, comparable to wild-type mice. The lower pressor response to ANG II in the mice expressing hSOD is consistent with a pressor role of superoxide anion in wild-type mice, most likely because it reacts with nitric oxide. Despite preventing the increase in superoxide anion and 3-nitrotyrosine, the aortic hypertrophic response to ANG II in vivo was unaffected by hSOD.


2016 ◽  
Vol 54 (4) ◽  
pp. 342-347
Author(s):  
M.H.S. Moxness ◽  
V. Bugten ◽  
W.M. Thorstensen ◽  
S. Nordgard ◽  
G. Bruskeland

Background: The differences in nasal geometry and function between OSA patients and healthy individuals are not known. Our aim was to evaluate the differences in nasal geometry and function using acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF) between an OSA population and healthy controls. Methodology: The study was designed as a prospective case-control study. Ninety-three OSA patients and 92 controls were enrolled from 2010 to 2015. The minimal cross-sectional area (MCA) and the nasal cavity volume (NCV) in two parts of the nose (MCA0-3/NCV0-3 and MCA3-5.2/NCV3-5.2) and PNIF were measured at baseline and after decongestion. Results: The mean MCA0-3 in the OSA group was 0.49 cm2; compared to 0.55 cm2 in controls. The mean NCV0-3 correspondingly was 2.51 cm3 compared to 2.73 cm3 in controls. PNIF measured 105 litres/minute in the OSA group and 117 litres/minute in the controls. Conclusions: OSA patients have a lower minimum cross-sectional area, nasal cavity volume and peak inspiratory flow compared to controls. Our study supports the view that changes in the nasal cavity may contribute to development of OSA.


2010 ◽  
Vol 299 (1) ◽  
pp. R268-R276 ◽  
Author(s):  
Anna C. Kayani ◽  
Graeme L. Close ◽  
Wolfgang H. Dillmann ◽  
Ruben Mestril ◽  
Malcolm J. Jackson ◽  
...  

Skeletal muscle atrophy and weakness are major contributors to frailty and impact significantly on quality of life of older people. Muscle aging is characterized by a loss of maximum tetanic force (Po) generation, primarily due to muscle atrophy, to which mitochondrial dysfunction is hypothesized to contribute. We hypothesized that lifelong overexpression of the mitochondrial heat shock protein (HSP) HSP10 in muscle of mice would protect against development of these deficits. Po generation by extensor digitorum longus muscles of adult and old wild-type and HSP10-overexpressing mice was determined in situ. Muscles were subjected to damaging lengthening contractions, and force generation was remeasured at 3 h or 28 days to examine susceptibility to, and recovery from, damage, respectively. Muscles of old wild-type mice had a 23% deficit in Po generation and a 10% deficit in muscle cross-sectional area compared with muscles of adult wild-type mice. Overexpression of HSP10 prevented this age-related fall in Po generation and reduction in cross-sectional area observed in muscles of old wild-type mice. Additionally, overexpression of HSP10 protected against contraction-induced damage independent of age but did not improve recovery if damage occurred. Preservation of muscle force generation and CSA by HSP10 overexpression was associated with protection against the age-related accumulation of protein carbonyls. Data demonstrate that development of age-related muscle weakness may not be inevitable and show, for the first time, that lifelong overexpression of an HSP prevents the age-related loss of Po generation. These findings support the hypothesis that mitochondrial dysfunction is involved in the development of age-related muscle deficits.


2020 ◽  
Author(s):  
Waruna Peiris ◽  
Flavia M Cicuttini ◽  
Maria Constantinou ◽  
Abbas Yaqobi ◽  
Sultana Monira Hussain ◽  
...  

Abstract Objective: To examine the associations between hip muscle cross-sectional area and hip pain and function in community-based individuals with mild-to-moderate hip osteoarthritis. Methods: This study included 27 participants with mild-to-moderate hip osteoarthritis. Cross-sectional area of hip muscles, including psoas major, rectus femoris, gluteus maximus, gluteus medius and minimus, adductor longus and magnus, obturator internus, and obturator externus, were measured from magnetic resonance images. Hip pain and function were evaluated using the Hip Disability and Osteoarthritis Outcome Score (HOOS). Results: After adjusting for age and gender, greater cross-sectional area of adductor longus and magnus was associated with a higher HOOS score in quality of life (regression coefficient 1.4, 95% confidence interval (CI) 0.2-2.7, p=0.02), activity of daily living (regression coefficient 1.3, 95% CI 0.1-2.6, p=0.04) and sport and recreation function (regression coefficient 1.6, 95% CI 0.1-3.0, p=0.04). Greater cross-sectional area of psoas major was associated with a higher quality of life score (regression coefficient 3.6, 95% CI -0.5 to 7.7, p=0.08). The cross-sectional area of hip muscles was not significantly associated with HOOS pain or symptom score. Conclusion: Greater cross-sectional area of hip adductors was associated with better function and quality of life in individuals with mild-to-moderate hip osteoarthritis. Greater cross-sectional area of hip flexors might be associated with better quality of life. These findings, while need to be confirmed in longitudinal studies, suggest that targeting the hip adductor and flexor muscles may improve function and quality of life in those with mild-to-moderate hip osteoarthritis.


1995 ◽  
Vol 79 (5) ◽  
pp. 1571-1577 ◽  
Author(s):  
B. J. Petrof ◽  
S. B. Gottfried ◽  
J. Eby ◽  
J. Lamanca ◽  
S. Levine

The present study tested the hypothesis that growth hormone (GH), an anabolic agent, could prevent the abnormalities of diaphragm structure and function associated with short-term administration of the corticosteroid triamcinolone (TR). During a 10-day period, male rats (n = 33) were assigned to control (CTL), TR (1 mg.kg-1.day-1 im), and TR-GH (2 mg.kg-1.day-1 im) groups. Diaphragm weight was significantly reduced in the TR and TR-GH animals compared with the CTL animals, but there was no difference in the diaphragm-to-body weight ratio. Fiber type (I, IIa, and IIx/b) proportions did not differ among the three groups. However, in TR rats there was a significant reduction in the contribution of type IIx/b fibers to total diaphragm cross-sectional area due to marked atrophy (approximately 42% decrease in mean fiber cross-sectional area). There was no significant reversal of TR-induced type IIx/b fiber atrophy by concomitant GH administration. TR and TR-GH groups both exhibited a left-ward shift of the force-frequency relationship and enhanced in vitro fatigue resistance, whereas maximal specific force was unaltered. We conclude that GH does not prevent corticosteroid-induced effects on the diaphragm under these conditions, possibly as a result of reduced nutritional intake associated with TR administration.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Feyen ◽  
Z Vermeulen ◽  
L Dugaucquier ◽  
D Hilfiker-Kleiner ◽  
V F M Segers ◽  
...  

Abstract Background Peripartum cardiomyopathy (PPCM) is a potentially life-threatening disease in women without known cardiovascular disease; PPCM is characterized by left ventricular (LV) systolic dysfunction towards the end of pregnancy and/or in the first months postpartum. The underlying mechanisms of PPCM are incompletely understood, but there is recent evidence that impaired cardiomyocyte expression of the tyrosine kinase ErbB4 receptor plays a role. ErbB4 is the main receptor of neuregulin-1, a protective and regenerative paracrine factor in the heart. Homozygous deletion of ErbB4 is lethal. Purpose To test the hypothesis that mice with heterozygous (HZ) cardiomyocyte-specific deletion of ErbB4 (ErbB4+/−) are more susceptible to PPCM. Methods Cardiac morphology and function was evaluated by echocardiography with a Vevo 2100 Imaging System during 2 pregnancies and 6 weeks postpartum (n=7–9) or during non-pregnant control conditions in HZ (ErbB4+/−) and wild type controls (n=9–10). Then, hearts were excised for analyses of myocardial fibrosis, macrophage infiltration, capillary density and cardiomyocyte cross sectional area. Results When compared to pregnant wild type controls, pregnant ErbB4+/− mice developed significant LV dilatation (2 weeks after the 2nd delivery: LVIDd +16% ± 2%, p<0.05) and dysfunction (6 weeks after the 2nd delivery: EF −23% ± 3%, p<0.001), increased heart to body weight ratio (+7% ± 4%, p<0.05) and increased cardiomyocyte cross sectional area (+28% ± 7%, p<0.01). Non-pregnant ErbB4+/− mice also developed LV dilatation and dysfunction, albeit slower than pregnant ErbB4+/− mice. On histology, however, myocardial tissue of pregnant ErbB4+/− mice did not show macrophage infiltration, neither fibrosis, nor reduced capillary density. Conclusions Heterozygous cardiomyocyte-specific deletion of ErbB4 sensitizes to peripartum LV dilatation and cardiomyocyte hypertrophy and systolic dysfunction without profound cardiac injury, features that are frequently present in PPCM patients and may explain their high chance for recovery. These data reinforce a compensatory role for neuregulin-ErbB4 signaling during hemodynamic overload, and confirm that this signaling pathway is important to protect the maternal heart during peripartum stress. Acknowledgement/Funding Fund scientific research Flanders; University Antwerp


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