Effects of transverse fiber stiffness and central tendon on displacement and shape of a simple diaphragm model

1997 ◽  
Vol 82 (5) ◽  
pp. 1626-1636 ◽  
Author(s):  
Aladin M. Boriek ◽  
Joseph R. Rodarte
Keyword(s):  
Orthotropic Material ◽  
Shape Change ◽  
Muscle Fibers ◽  
Muscle Length ◽  
Diaphragm Muscle ◽  
Direction Transverse ◽  
Diaphragmatic Muscle ◽  
Transverse Fiber ◽  
Wide Range ◽  
Length Changes

Boriek, Aladin M., and Joseph R. Rodarte. Effects of transverse fiber stiffness and central tendon on displacement and shape of a simple diaphragm model. J. Appl. Physiol. 82(5): 1626–1636, 1997.—Our previous experimental results (A. M. Boriek, S. Lui, and J. R. Rodarte. J. Appl. Physiol. 75: 527–533, 1993 and A. M. Boriek, T. A. Wilson, and J. R. Rodarte. J. Appl. Physiol. 76: 223–229, 1994) showed that 1) costal diaphragm shape is similar at functional residual capacity and end inspiration regardless of whether the diaphragm muscle shortens actively (increased tension) or passively (decreased tension); 2) diaphragmatic muscle length changes minimally in the direction transverse to the muscle fibers, suggesting the diaphragm may be inextensible in that direction; and 3) the central tendon is not stretched by physiological stresses. A two-dimensional orthotropic material has two different stiffnesses in orthogonal directions. In the plane tangent to the muscle surface, these directions are along the fibers and transverse to the fibers. We wondered whether orthotropic material properties in the muscular region of the diaphragm and inextensibility of the central tendon might contribute to the constancy of diaphragm shape. Therefore, in the present study, we examined the effects of stiffness transverse to muscle fibers and inextensibility of the central tendon on diaphragmatic displacement and shape. Finite element hemispherical models of the diaphragm were developed by using pressurized isotropic and orthotropic membranes with a wide range of stiffness ratios. We also tested heterogeneous models, in which the muscle sheet was an orthotropic material, having transverse fiber stiffness greater than that along the fibers, with the central tendon being an inextensible isotropic cap. These models revealed that increased transverse stiffness limits the shape change of the diaphragm. Furthermore, an inextensible cap simulating the central tendon dramatically limits the change in shape as well as the membrane displacement in response to pressure. These findings provide a plausible mechanism by which the diaphragm maintains similar shapes despite different physiological loads. This study suggests that changes of diaphragm shape are restricted because the central tendon is essentially inextensible and stiffness in the direction transverse to the muscle fibers is greater than stiffness along the fibers.

scholarly journals Passive mechanics of muscle tendinous junction of canine diaphragm

2005 ◽  
Vol 98 (4) ◽  
pp. 1328-1333 ◽  
Author(s):  
Willy Hwang ◽  
Neil G. Kelly ◽  
Aladin M. Boriek
Keyword(s):  
Strain Curve ◽  
Muscle Stiffness ◽  
Diaphragm Muscle ◽  
Passive Stiffness ◽  
Muscle Strain ◽  
Direction Transverse ◽  
Diaphragmatic Muscle ◽  
Unloaded State ◽  
Tendon Strain

The diaphragmatic muscle tendon is a biaxially loaded junction in vivo. Stress-strain relations along and transverse to the fiber directions are important in understanding its mechanical properties. We hypothesized that 1) the central tendon possesses greater passive stiffness than adjacent muscle, 2) the diaphragm muscle is anisotropic, whereas the central tendon near the junction is essentially isotropic, and 3) a gradient in passive stiffness exists as one approaches the muscle-tendinous junction (MTJ). To investigate these hypotheses, we conducted uniaxial and biaxial mechanical loading on samples of the MTJ excised from the midcostal region of dog diaphragm. We measured passive length-tension relationships of the muscle, tendon, and MTJ in the direction along the muscle fibers as well as transverse to the fibers. The MTJ was slack in the unloaded state, resulting in a J-shaped passive tension-strain curve. Generally, muscle strain was greater than that of MTJ, which was greater than tendon strain. In the muscular region, stiffness in the direction transverse to the fibers is much greater than that along the fibers. The central tendon is essentially inextensible in the direction transverse to the fibers as well as along the fibers. Our data demonstrate the existence of more pronounced anisotropy in the muscle than in the tendon near the junction. Furthermore, a gradient in muscle stiffness exists as one approaches the MTJ, consistent with the hypothesis of continuous passive stiffness across the MTJ.

Effect of theophylline on the velocity of diaphragmatic muscle shortening

1988 ◽  
Vol 65 (3) ◽  
pp. 1410-1415
Author(s):  
G. S. Supinski ◽  
J. S. Arnold ◽  
S. G. Kelsen
Keyword(s):  
Muscle Length ◽  
Neural Firing ◽  
Shortening Velocity ◽  
Diaphragmatic Muscle ◽  
Wide Range ◽  
Velocity Of Shortening ◽  
Muscle Shortening ◽  
Time Required ◽  
Unloaded Velocity

The present study examined the effect of theophylline on the shortening velocity of submaximally activated diaphragmatic muscle (i.e., muscles were activated by the use of a level of stimulation, 50 Hz, within the range of phrenic neural firing frequencies achieved during breathing, whereas maximum activation is achieved at 300 Hz). Experiments were performed in vitro on strips of diaphragmatic muscle obtained from 21 Syrian hamsters. Muscle shortening velocity was assessed during isotonic contractions against a range of afterloads, and Hill's characteristic equation was used to calculate velocity at zero load. In addition, unloaded shortening velocity was also measured by the slack test, i.e., from the time required for muscles to take up slack after a sudden reduction in muscle length. Theophylline (160 mg/l) increased the velocity of muscle shortening against a wide range of external loads (0-14 N/cm2) and increased the extrapolated unloaded velocity of shortening from 6.4 +/- 0.9 to 7.9 +/- 1.1 (SE) lengths/s (P less than 0.01). Theophylline reduced the time required to take up slack for any given step change in muscle length, increasing the unloaded velocity of shortening assessed by the slack test from 7.6 +/- 0.9 to 9.3 +/- 1.1 lengths/s (P less than 0.002). The effect of theophylline on diaphragmatic shortening velocity was evident at concentrations as low as 40 mg/l and increased progressively as theophylline concentrations were increased to 320 mg/l. Theophylline increased the shortening velocity of fatigued as well as fresh muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical determinants of isotonic relaxation in isolated diaphragm muscle

1993 ◽  
Vol 75 (5) ◽  
pp. 2265-2272 ◽  
Author(s):  
C. Coirault ◽  
D. Chemla ◽  
N. Pery ◽  
I. Suard ◽  
Y. Lecarpentier
Keyword(s):  
Muscle Length ◽  
Diaphragm Muscle ◽  
Process Time ◽  
Experimental Conditions ◽  
Total Load ◽  
Main Determinant ◽  
Contraction Phase ◽  
Stimulation Mode ◽  
Wide Range ◽  
Abrupt Changes

Determinants of lengthening velocity have not been investigated in the diaphragm muscle. This study was undertaken to define the mechanical determinants of isotonic relaxation rate over the entire load continuum in isolated rat diaphragm (n = 30). We tested the hypothesis that the determinants of lengthening could include loading conditions, namely, preload and afterload; abrupt changes of load during the contraction phase; end-shortening muscle length (ESL); extent of shortening (delta L); time; stimulation mode; and stimulation frequency. In afterloaded contractions preloaded at optimal initial length and stimulated in tetanus at 30 Hz, peak lengthening velocity (+dL/dtmax) was linearly related to delta L, ESL, and/or total load. Varying initial muscle length, ESL, afterload, or the load imposed on the muscle during the isotonic lengthening process did not modify +dL/dtmax vs. delta L relationship, whereas +dL/dtmax vs. load and +dL/dtmax vs. ESL relationships were modified by these procedures. For a given delta L, +dL/dtmax could be modified when lengthening was delayed by reversing the relaxation sequence and when twitch and tetanus modes were compared. In conclusion, our results demonstrate that in isolated diaphragm muscle, delta L is the main determinant of +dL/dtmax over a wide range of loads and under various experimental conditions, independent of ESL and initial muscle length and independent of the load imposed on the muscle during the lengthening process. Time and stimulation mode were also shown to modulate the lengthening rate in diaphragm muscle.

scholarly journals Acquired Diaphragmatic Eventration in a Dog

2018 ◽  
Vol 47 ◽  
Author(s):  
Bruna Marquardt Lucio ◽  
Rafael Almeida Fighera ◽  
Saulo Tadeu Lemos Pinto Filho ◽  
Mariana Martins Flores
Keyword(s):  
Diaphragmatic Hernia ◽  
Phrenic Nerve ◽  
Polypropylene Mesh ◽  
Muscle Fibers ◽  
Exercise Intolerance ◽  
Diaphragm Muscle ◽  
Thoracic Cavity ◽  
Diaphragmatic Eventration ◽  
Diaphragmatic Muscle ◽  
Normal Diaphragm

Background: Diaphragmatic eventration is characterized by weakness of the diaphragmatic muscle, which leads to cranial dislocation of the affected diaphragm and, ultimately, in dyspnea. This condition is rare in humans and even rarer in animals, and may be congenital or acquired. The acquired form is less commom and may be induced by trauma or inflammation and neoplastic invasion of the phrenic nerve. Here, we report a case of acquired diaphragmatic eventration in a dog, with the aim of increasing the knowledge of this condition in animals and helping others to recognize and treat future cases.Case: A 12-year-old male dachshund presented with severe dyspnea, exercise intolerance and episodes of coughing. Based on a physical examination and imaging, the main suspicion was a diaphragmatic hernia, and surgery was performed. When the surgeon entered the thoracic cavity, an extremely thin - yet, intact - right hemidiaphragm was observed. The left side of the diaphragm was normal. A polypropylene mesh was sutured to the affected diaphragm in an attempt to strengthen the hemidiaphragmatic muscles and prevent further insinuations of viscera into the thoracic cavity. The dog developed bronchopneumonia, postoperatively, and was hospitalized and treated with antibiotics, analgesics and support medication. However, the dog died five days after surgery. A postmortem examination revealed that the right side of the diaphragm was markedly thin and flaccid. Diaphragm samples were collected for histopathological examination. For comparison, a sample of normal diaphragm was collected from a same age, matched dachshund that died due to an unrelated condition. This tissue was called “diaphragm control”, and it was collected in order to compare the histologic features of a normal diaphragm muscle with the affected one. Histopathology revealed a marked reduction of muscle fibers. In the affected sample, replacement of these fibers by fibrous connective tissue and a marked infiltration of fat were seen among the remaining muscle fibers.  Multifocal areas of necrosis were also observed affecting some muscles fibers. Microscopic comparisons of both diaphragm samples (affected vs. control) revealed a drastic difference in the amount of muscle fibers and fat, corroborating the intense diaphragmatic atrophy observed in the diaphragm from the affected dog. Based on clinical presentation, the gross lesions observed during surgery and later during the post mortem examination, and histopathological findings, a definitive diagnosis of acquired diaphragmatic eventration was established.Discussion: Diaphragmatic eventration is rarely reported in small animal clinics and thus may be confused with other conditions. It must be mainly differentiated from diaphragmatic hernia and should be considered as a differential diagnosis when an animal, regardless of age, presents with dyspnea, apathy and coughing episodes.  On suspecting diaphragmatic eventration, surgical intervention should be carried out as soon as possible. The recommended treatment is plication of the affected hemidiaphragm. However, in the present case, a polypropylene mesh was sutured to the affected area to support the atrophic muscles. It is thought that, trauma injured the dog’s phrenic nerve, affecting right hemidiaphragmatic innervation, and generating progressive atrophy of diaphragmatic muscle fibers. Subsequently, the dog developed diaphragmatic eventration due to diaphragmatic fragility. Diaphragmatic eventration is a very rare disorder in small animals and can be difficult to diagnose based solely on physical and radiographic examinations.

Characterization of a radula opener neuromuscular system in Aplysia

1996 ◽  
Vol 76 (2) ◽  
pp. 1267-1281 ◽  
Author(s):  
C. G. Evans ◽  
S. Rosen ◽  
I. Kupfermann ◽  
K. R. Weiss ◽  
E. C. Cropper
Keyword(s):  
Motor Neurons ◽  
Action Potentials ◽  
Muscle Tension ◽  
Muscle Fibers ◽  
Muscle Length ◽  
Excitatory Input ◽  
Muscle Contractions ◽  
Synaptic Activity ◽  
Length Changes ◽  
Stimulation Of

1. Several lines of evidence suggest that the I7-I10 muscle group contributes to the radula opening phase of behavior in Aplysia; 1) extracellular stimulation of these muscles in reduced preparations causes the halves of the radula to separate, 2) synaptic activity can be recorded from muscles I7-I10 in intact animals when the radula is opening, and 3) motor neurons innervating I7-I10 are activated out of phase with retractor/closer motor neurons during cycles of buccal activity driven by the cerebral-to-buccal interneuron 2 (CBI-2). 2. All of the opener muscles are innervated by the B48 neurons, a bilaterally symmetrical pair of cholinergic motor neurons. B48 neurons produce excitatory junction potentials (EJPs) in opener muscle fibers that summate to produce muscle contractions. Contraction size is determined by the size of depolarization in muscle fibers and/or by action potentials that are triggered by summation of B48-evoked EJPs. 3. In addition to input from B48 neurons, opener muscles also receive excitatory input from the cholinergic multiaction neurons B4/B5. EJPs evoked by stimulation of neurons B4/B5 are 1/10 the size of B48-evoked EJPs. Consequently, changes in muscle tension produced by B4/B5 activity are relatively small. In contrast to B48 neurons, neurons B4/B5 are likely to be active during the closing/retraction phase of behavior. During cycles of buccal activity driven by neuron CBI-2, neurons B4/B5 fire in phase with closer/retractor motor neurons. Thus opener muscles may develop a modest amount of tension during the closing/retraction phase of behavior as a result of synaptic input from neurons B4/B5. 4. Opener muscles may also develop tension during closing/retraction simply by virtue of the fact that they have been stretched. When isolated opener muscles are lengthened, depolarizations are recorded from individual muscle fibers, and muscle tension increases. With sufficient changes in fiber length, action potentials are elicited. These action potentials produce twitchlike muscle contractions that become rhythmic with maintained stretch. Stretch-activated depolarizations are generally first apparent when muscle length is increased by 1 mm. Length changes of 4-5 mm are generally necessary to elicit twitchlike muscle contractions. Changes of 1-2 mm in muscle length are observed when the opener muscle's antagonist, the accessory radula closer, is activated in reduced preparations. 5. Stretch may also modulate B48-induced contractions of the opener muscles. When muscle length is increased, B48-elicited contractions of the I7 muscle are larger. These increases in contraction amplitude are accompanied by decreases in contraction latency. 6. We conclude that muscles I7-I10 contract vigorously in response to strong excitatory input from neuron B48 and contribute to radula opening. Stretch may potentiate this activity. Thus, if radula closer muscles contract vigorously and pull on the opener muscles, the opener muscles will respond by contracting more vigorously themselves. This may be a mechanism for maintaining amplitude relationships between antagonistic muscles. Additionally, it is likely that the opener muscles will develop at least a modest amount of tension during closure/retraction of the radula. Part of this activation may derive from the weak excitatory input that the muscles receive from neurons B4/B5. Another part may derive from the stretch. One function of this co-contraction may be to act as a brake on closure, bringing this phase of feeding behavior to a smooth halt.

Microstructural characterization of laser-melted/roller-quenched dicalcium silicate

1988 ◽  
Vol 46 ◽  
pp. 582-583
Author(s):  
C. J. Chan ◽  
K. R. Venkatachari ◽  
W. M. Kriven ◽  
J. F. Young
Keyword(s):  
Particle Size ◽  
Raw Materials ◽  
Shape Change ◽  
Microstructural Characterization ◽  
Particle Size Effect ◽  
Dicalcium Silicate ◽  
Laser Melting ◽  
Uniform Size ◽  
Cell Shape Change ◽  
Wide Range

Dicalcium silicate (Ca2SiO4) is a major component of Portland cement. It has also been investigated as a potential transformation toughener alternative to zirconia. It has five polymorphs: α, α'H, α'L, β and γ. Of interest is the β-to-γ transformation on cooling at about 490°C. This transformation, accompanied by a 12% volume increase and a 4.6° unit cell shape change, is analogous to the tetragonal-to-monoclinic transformation in zirconia. Due to the processing methods used, previous studies into the particle size effect were limited by a wide range of particle size distribution. In an attempt to obtain a more uniform size, a fast quench rate involving a laser-melting/roller-quenching technique was investigated.The laser-melting/roller-quenching experiment used precompacted bars of stoichiometric γ-Ca2SiO4 powder, which were synthesized from AR grade CaCO3 and SiO2xH2O. The raw materials were mixed by conventional ceramic processing techniques, and sintered at 1450°C. The dusted γ-Ca2SiO4 powder was uniaxially pressed into 0.4 cm x 0.4 cm x 4 cm bars under 34 MPa and cold isostatically pressed under 172 MPa. The γ-Ca2SiO4 bars were melted by a 10 KW-CO2 laser.

scholarly journals Effect of nitrofen in the final stages of development of the diaphragm muscle in rats

2013 ◽  
Vol 28 (suppl 1) ◽  
pp. 13-18 ◽  
Author(s):  
Frances Lilian Lanhellas Gonçalves ◽  
Fábio Santana de Oliveira ◽  
Augusto Frederico Schmidt ◽  
Luís Antônio Violin Dias Pereira ◽  
Rodrigo Melo Gallindo ◽  
...  
Keyword(s):  
Body Weight ◽  
Congenital Diaphragmatic Hernia ◽  
Olive Oil ◽  
Diaphragmatic Hernia ◽  
Muscle Fibers ◽  
Diaphragm Muscle ◽  
External Control ◽  
Stages Of Development ◽  
Pregnant Rats ◽  
Histological Staining

PURPOSE: To evaluate the expression of myosin in muscle fibers of the diaphragm in experimental congenital diaphragmatic hernia (CDH). METHODS: Fetuses of pregnant rats were divided into four groups: External Control (EC), composed of non-manipulated rats; Nitrofen, composed of pregnant rats that received 100 mg of nitrofen (2,4-dichloro-4'nitrodiphenyl ether) diluted in olive oil on gestational day (GD) 9.5, whose fetuses developed CDH (N+) or not (N-), and Olive Oil Placebo (OO), composed of pregnant rats that received the oil on the same GD. The fetuses were collected on GD 18.5, 19.5, 20.5 and 21.5 (term = 22 days). We obtained body weight (BW) and photographed the diaphragm area (DA), hernia area (HA) and subsequent calculated the HA/DA ratio in N+ group. Samples of Diaphragm muscle were processed for histological staining with H/E and immunohistochemistry (IHQ) for myosin.} RESULTS: The fetuses of N- and N+ groups had decreased BW and DA compared to EC and OO groups (p <0.001). HA was decreased on GD 18.5 compared to 21.5 (p <0.001) and the HA/DA ratio showed no difference. IHQ showed decreased expression of myosin in nitrofen groups. CONCLUSION: CDH induced by nitrofen model contributes to the understanding of muscularization in the formation of the diaphragm where the myosin expression is decreased.

Muscle dynamics in skipjack tuna: timing of red muscle shortening in relation to activation and body curvature during steady swimming

1999 ◽  
Vol 202 (16) ◽  
pp. 2139-2150 ◽  
Author(s):  
R.E. Shadwick ◽  
S.L. Katz ◽  
K.E. Korsmeyer ◽  
T. Knower ◽  
J.W. Covell
Keyword(s):  
Fork Length ◽  
Muscle Length ◽  
The Body ◽  
Emg Activity ◽  
Skipjack Tuna ◽  
Force Transmission ◽  
Muscle Strain ◽  
Muscle Shortening ◽  
Red Muscle ◽  
Length Changes

Cyclic length changes in the internal red muscle of skipjack tuna (Katsuwonus pelamis) were measured using sonomicrometry while the fish swam in a water tunnel at steady speeds of 1.1-2.3 L s(−)(1), where L is fork length. These data were coupled with simultaneous electromyographic (EMG) recordings. The onset of EMG activity occurred at virtually the same phase of the strain cycle for muscle at axial locations between approximately 0.4L and 0.74L, where the majority of the internal red muscle is located. Furthermore, EMG activity always began during muscle lengthening, 40–50 prior to peak length, suggesting that force enhancement by stretching and net positive work probably occur in red muscle all along the body. Our results support the idea that positive contractile power is derived from all the aerobic swimming muscle in tunas, while force transmission is provided primarily by connective tissue structures, such as skin and tendons, rather than by muscles performing negative work. We also compared measured muscle length changes with midline curvature (as a potential index of muscle strain) calculated from synchronised video image analysis. Unlike contraction of the superficial red muscle in other fish, the shortening of internal red muscle in skipjack tuna substantially lags behind changes in the local midline curvature. The temporal separation of red muscle shortening and local curvature is so pronounced that, in the mid-body region, muscle shortening at each location is synchronous with midline curvature at locations that are 7–8 cm (i.e. 8–10 vertebral segments) more posterior. These results suggest that contraction of the internal red muscle causes deformation of the body at more posterior locations, rather than locally. This situation represents a unique departure from the model of a homogeneous bending beam, which describes red muscle strain in other fish during steady swimming, but is consistent with the idea that tunas produce thrust by motion of the caudal fin rather than by undulation of segments along the body.

Summation of motor unit tensions in the tibialis posterior muscle of the cat under isometric and nonisometric conditions

1991 ◽  
Vol 66 (6) ◽  
pp. 1838-1846 ◽  
Author(s):  
R. K. Powers ◽  
M. D. Binder
Keyword(s):  
Motor Unit ◽  
Muscle Fibers ◽  
Stimulus Frequency ◽  
Muscle Length ◽  
Motor Units ◽  
Force Transducer ◽  
Tibialis Posterior ◽  
Single Motor Units ◽  
Individual Motor ◽  
Stimulation Of

1. The tension produced by the combined stimulation of two to four single motor units of the cat tibialis posterior muscle was compared with the algebraic sum of the tensions produced by each individual motor unit. Comparisons were made under isometric conditions and during imposed changes in muscle length. 2. Under isometric conditions, the tension resulting from combined stimulation of units displayed marked nonlinear summation, as previously reported in other cat hindlimb muscles. On average, the measured tension was approximately 20% greater than the algebraic sum of the individual unit tensions. However, small trapezoidal movements imposed on the muscle during stimulation significantly reduced the degree of nonlinear summation both during and after the movement. This effect was seen with imposed movements as small as 50 microns. 3. The degree of nonlinear summation was not dependent on motor unit size or on stimulus frequency. The effect was also unrelated to tendon compliance because the degree of nonlinear summation of motor unit forces was unaffected by the inclusion of different amounts of the external tendon between the muscle and the force transducer. 4. Our results support previous suggestions that the force measured when individual motor units are stimulated under isometric conditions is reduced by friction between the active muscle fibers and adjacent passive fibers. These frictional effects are likely to originate in the connective tissue matrix connecting adjacent muscle fibers. However, because these effects are virtually eliminated by small movements, linear summation of motor unit tensions should occur at low force levels under nonisometric conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Exercise-induced alterations and loss of sarcomeric M-line organization in the diaphragm muscle of obscurin knockout mice

2017 ◽  
Vol 312 (1) ◽  
pp. C16-C28 ◽  
Author(s):  
D. Randazzo ◽  
B. Blaauw ◽  
C. Paolini ◽  
E. Pierantozzi ◽  
S. Spinozzi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fibers ◽  
Detailed Examination ◽  
Diaphragm Muscle ◽  
Hindlimb Muscles ◽  
Skeletal Muscle Fibers ◽  
Exercise Induced ◽  
Old Mice ◽  
Ankyrin B ◽  
Deficient Mice

We recently reported that skeletal muscle fibers of obscurin knockout (KO) mice present altered distribution of ankyrin B (ankB), disorganization of the subsarcolemmal microtubules, and reduced localization of dystrophin at costameres. In addition, these mice have impaired running endurance and increased exercise-induced sarcolemmal damage compared with wild-type animals. Here, we report results from a combined approach of physiological, morphological, and structural studies in which we further characterize the skeletal muscles of obscurin KO mice. A detailed examination of exercise performance, using different running protocols, revealed that the reduced endurance of obscurin KO animals on the treadmill depends on exercise intensity and age. Indeed, a mild running protocol did not evidence significant differences between control and obscurin KO mice, whereas comparison of running abilities of 2-, 6-, and 11-mo-old mice exercised at exhaustion revealed a progressive age-dependent reduction of the exercise tolerance in KO mice. Histological analysis indicated that heavy exercise induced leukocyte infiltration, fibrotic connective tissue deposition, and hypercontractures in the diaphragm of KO mice. On the same line, electron microscopy revealed that, in the diaphragm of exercised obscurin KO mice, but not in the hindlimb muscles, both M-line and H-zone of sarcomeres appeared wavy and less defined. Altogether, these results suggest that obscurin is required for the maintenance of morphological and ultrastructural integrity of skeletal muscle fibers against damage induced by intense mechanical stress and point to the diaphragm as the skeletal muscle most severely affected in obscurin-deficient mice.

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