scholarly journals Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension

2016 ◽  
Vol 311 (1) ◽  
pp. L20-L28 ◽  
Author(s):  
Emmy Manders ◽  
Peter I. Bonta ◽  
Jaap J. Kloek ◽  
Petr Symersky ◽  
Harm-Jan Bogaard ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Muscle Fiber ◽  
Ex Vivo ◽  
Muscle Fibers ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Inspiratory Muscle ◽  
Force Generation ◽  
Diaphragm Muscle ◽  
Fast Twitch

Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients ( N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls ( N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast-twitch muscle fibers of CTEPH patients, resulting in a ∼40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 μM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients.

Diaphragm Muscle Fiber Weakness in Pulmonary Hypertension

2011 ◽  
Vol 183 (10) ◽  
pp. 1411-1418 ◽  
Author(s):  
Frances S. de Man ◽  
Hieronymus W. H. van Hees ◽  
M. Louis Handoko ◽  
Hans W. Niessen ◽  
Ingrid Schalij ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Muscle Fiber ◽  
Diaphragm Muscle

A Method To Study In Vivo Protein Synthesis In Slow- And Fast-twitch Human Muscle Fibers

2010 ◽  
Vol 42 ◽  
pp. 64
Author(s):  
Jared M. Dickinson ◽  
Jonah D. Lee ◽  
Bridget E. Sullivan ◽  
Matthew P. Harber ◽  
Scott W. Trappe ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Fibers ◽  
Human Muscle ◽  
Fast Twitch ◽  
In Vivo Protein Synthesis

scholarly journals A new method to study in vivo protein synthesis in slow- and fast-twitch muscle fibers and initial measurements in humans

2010 ◽  
Vol 108 (5) ◽  
pp. 1410-1416 ◽  
Author(s):  
J. M. Dickinson ◽  
J. D. Lee ◽  
B. E. Sullivan ◽  
M. P. Harber ◽  
S. W. Trappe ◽  
...  
Keyword(s):  
Fiber Type ◽  
Vastus Lateralis ◽  
Muscle Fibers ◽  
Human Muscle ◽  
Synthesis Rate ◽  
Mhc I ◽  
Fast Twitch ◽  
Mixed Protein ◽  
Mhc Iia

The aim of this study was to develop an approach to directly assess protein fractional synthesis rate (FSR) in isolated human muscle fibers in a fiber type-specific fashion. Individual muscle fibers were isolated from biopsies of the vastus lateralis (VL) and soleus (SOL) obtained from eight young men during a primed, continuous infusion of [5,5,5-2H3]leucine performed under basal conditions. To determine mixed protein FSR, a portion of each fiber was used to identify fiber type, fibers of the same type were pooled, and the [5,5,5-2H3]leucine enrichment was determined via GC-MS. Processing isolated slow-twitch [myosin heavy chain (MHC) I] and fast-twitch (MHC IIa) fibers for mixed protein bound [5,5,5-2H3]leucine enrichment yielded mass ion chromatographic peaks that were similar in shape, abundance, and measurement reliability as tissue homogenates. In the VL, MHC I fibers exhibited a 33% faster ( P < 0.05) mixed protein FSR compared with MHC IIa fibers (0.068 ± 0.006 vs. 0.051 ± 0.003%/h). MHC I fibers from the SOL (0.060 ± 0.005%/h) and MHC I fibers from the VL displayed similar ( P > 0.05) mixed protein FSR. Feasibility of processing isolated human muscle fibers for analysis of myofibrillar protein [5,5,5-2H3]leucine enrichment was also confirmed in non-fiber-typed pooled fibers from the VL. These methods can be applied to the study of fiber type-specific responses in human skeletal muscle. The need for this level of investigation is underscored by the different contributions of each fiber type to whole muscle function and the numerous distinct adaptive functional and metabolic changes in MHC I and MHC II fibers originating from the same muscle.

Absence of regional differences in the size and oxidative capacity of diaphragm muscle fibers

1987 ◽  
Vol 63 (3) ◽  
pp. 1076-1082 ◽  
Author(s):  
G. C. Sieck ◽  
R. D. Sacks ◽  
C. E. Blanco
Keyword(s):  
Muscle Fibers ◽  
Continuous Distribution ◽  
Oxidative Capacity ◽  
Cross Sectional Area ◽  
Diaphragm Muscle ◽  
Type I ◽  
Fiber Types ◽  
Sectional Area ◽  
Cross Sectional ◽  
Fast Twitch

The oxidative capacity and cross-sectional area of muscle fibers were compared between the costal and crural regions of the cat diaphragm and across the abdominal-thoracic extent of the muscle. Succinate dehydrogenase (SDH) activity of individual fibers was quantified using a microphotometric procedure implemented on an image-processing system. In both costal and crural regions, population distributions of SDH activities were unimodal for both type I and II fibers. The continuous distribution of SDH activities for type II fibers indicated that no clear threshold exists for the subclassification of fibers based on differences in oxidative capacity (e.g., the classification of fast-twitch glycolytic and fast-twitch oxidative glycolytic fiber types). No differences in either SDH activity or cross-sectional area were noted between fiber populations of the costal and crural regions. Differences in SDH activity and cross-sectional area were noted, however, between fiber populations located on the abdominal and thoracic sides of the costal region. Both type I and II fibers on the abdominal side of the costal diaphragm were larger and more oxidative than comparable fibers on the thoracic side.

scholarly journals The Neuromuscular Junction in Health and Disease: Molecular Mechanisms Governing Synaptic Formation and Homeostasis

2020 ◽  
Vol 13 ◽  
Author(s):  
Pedro M. Rodríguez Cruz ◽  
Judith Cossins ◽  
David Beeson ◽  
Angela Vincent
Keyword(s):  
Neuromuscular Junction ◽  
Action Potential ◽  
Motor Neuron ◽  
Muscle Fiber ◽  
Neuromuscular Transmission ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Motor Nerve ◽  
And Function

The neuromuscular junction (NMJ) is a highly specialized synapse between a motor neuron nerve terminal and its muscle fiber that are responsible for converting electrical impulses generated by the motor neuron into electrical activity in the muscle fibers. On arrival of the motor nerve action potential, calcium enters the presynaptic terminal, which leads to the release of the neurotransmitter acetylcholine (ACh). ACh crosses the synaptic gap and binds to ACh receptors (AChRs) tightly clustered on the surface of the muscle fiber; this leads to the endplate potential which initiates the muscle action potential that results in muscle contraction. This is a simplified version of the events in neuromuscular transmission that take place within milliseconds, and are dependent on a tiny but highly structured NMJ. Much of this review is devoted to describing in more detail the development, maturation, maintenance and regeneration of the NMJ, but first we describe briefly the most important molecules involved and the conditions that affect their numbers and function. Most important clinically worldwide, are myasthenia gravis (MG), the Lambert-Eaton myasthenic syndrome (LEMS) and congenital myasthenic syndromes (CMS), each of which causes specific molecular defects. In addition, we mention the neurotoxins from bacteria, snakes and many other species that interfere with neuromuscular transmission and cause potentially fatal diseases, but have also provided useful probes for investigating neuromuscular transmission. There are also changes in NMJ structure and function in motor neuron disease, spinal muscle atrophy and sarcopenia that are likely to be secondary but might provide treatment targets. The NMJ is one of the best studied and most disease-prone synapses in the nervous system and it is amenable to in vivo and ex vivo investigation and to systemic therapies that can help restore normal function.

scholarly journals Muscle hypertrophy and muscle strength: dependent or independent variables? A provocative review

2020 ◽  
Author(s):  
Carlos Reggiani ◽  
Stefano Schiaffino
Keyword(s):  
Muscle Strength ◽  
Muscle Hypertrophy ◽  
Muscle Force ◽  
Genetic Manipulation ◽  
Ex Vivo ◽  
Muscle Fibers ◽  
Muscle Size ◽  
Hormone Administration ◽  
Proportional Increase

The question whether the muscle hypertrophy induced by resistance training, hormone administration or genetic manipulation is accompanied by a proportional increase in muscle strength is still open. This review summarizes and analyses data obtained in human and rodent muscles in studies that have monitored in parallel changes in muscle size and changes in muscle force, measured in isometric contractions in vivo, in isolated muscles ex vivo (in rodents) and in single muscle fibers. Although a general positive relation exists among the two variables, a number of studies show a clear dissociation with increase of muscle size with no change or even decrease in strength and, vice versa, increase in strength without increase in size. The possible mechanisms of such dissociation, which involves neural motor control and/or cellular and molecular adaptations of muscle fibers, are briefly discussed.

scholarly journals Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation

2014 ◽  
Vol 307 (6) ◽  
pp. L460-L470 ◽  
Author(s):  
Pleuni E. Hooijman ◽  
Marinus A. Paul ◽  
Ger J. M. Stienen ◽  
Albertus Beishuizen ◽  
Hieronymus W. H. Van Hees ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Muscle Fibers ◽  
Calcium Sensitivity ◽  
Diaphragm Muscle ◽  
Cross Sectional ◽  
Fast Twitch Muscle ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Kinetics Of ◽  
Contractile Performance

Several studies have indicated that diaphragm dysfunction develops in patients on mechanical ventilation (MV). Here, we tested the hypothesis that the contractility of sarcomeres, i.e., the smallest contractile unit in muscle, is affected in humans on MV. To this end, we compared diaphragm muscle fibers of nine brain-dead organ donors (cases) that had been on MV for 26 ± 5 h with diaphragm muscle fibers from nine patients (controls) undergoing surgery for lung cancer that had been on MV for less than 2 h. In each diaphragm specimen we determined 1) muscle fiber cross-sectional area in cryosections by immunohistochemical methods and 2) the contractile performance of permeabilized single muscle fibers by means of maximum specific force, kinetics of cross-bridge cycling by rate of tension redevelopment, myosin heavy chain content and concentration, and calcium sensitivity of force of slow-twitch and fast-twitch muscle fibers. In case subjects, we noted no statistically significant decrease in outcomes compared with controls in slow-twitch or fast-twitch muscle fibers. These observations indicate that 26 h of MV of humans is not invariably associated with changes in the contractile performance of sarcomeres in the diaphragm.

Muscle fiber type distribution and architecture of the cat diaphragm

1983 ◽  
Vol 55 (5) ◽  
pp. 1386-1392 ◽  
Author(s):  
G. C. Sieck ◽  
R. R. Roy ◽  
P. Powell ◽  
C. Blanco ◽  
V. R. Edgerton ◽  
...  
Keyword(s):  
Muscle Fiber ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Muscle Fiber Type ◽  
Diaphragmatic Muscle ◽  
Band Area ◽  
Type Composition ◽  
Abdominal Surface ◽  
Fiber Type Distribution ◽  
Fast Twitch

Three types of diaphragmatic muscle fibers were identified histochemically in the sternal, costal, and crural regions of the cat diaphragm. Differences in the proportion of each muscle fiber type were observed between the abdominal and thoracic surfaces of the diaphragm but not among the different regions. A higher percentage of slow-twitch oxidative fibers was noted on the abdominal surface, whereas more fast-twitch fibers (fast-twitch oxidative-glycolytic and fast-twitch glycolytic) were found on the thoracic surface. Differences in muscle architecture were observed between diaphragmatic regions, but not between abdominal and thoracic sides. Overall, muscle fibers were longer in the crural regions, with the longest fibers being found in the crossing-band area of the crura. In the costal regions, fibers were longest in the center and became shorter toward the ventral and dorsal extent of these regions. Fiber lengths were similar throughout the sternal region. In each diaphragmatic region, the length of fibers extended from the origin of the muscle to its insertion. We conclude that functional differences between diaphragmatic regions could be attributed to fiber length and/or orientation, but not to differences in fiber-type composition.

scholarly journals Insulin resistance for glucose uptake and Akt2 phosphorylation in the soleus, but not epitrochlearis, muscles of old vs. adult rats

2010 ◽  
Vol 108 (6) ◽  
pp. 1631-1640 ◽  
Author(s):  
Naveen Sharma ◽  
Edward B. Arias ◽  
Mini P. Sajan ◽  
James G. MacKrell ◽  
Abhijit D. Bhat ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Brown Norway ◽  
Adult Rats ◽  
Insulin Resistant ◽  
Age Related ◽  
Old Rats ◽  
Fast Twitch

The slow-twitch soleus, but not fast-twitch muscle, of old vs. adult rats has previously been demonstrated to become insulin resistant for in vivo glucose uptake. We probed cellular mechanisms for the age effect by assessing whether insulin resistance for glucose uptake was an intrinsic characteristic of the muscle ex vivo and by analyzing key insulin signaling steps. We hypothesized that isolated soleus and epitrochlearis (fast-twitch) muscles from old (25 mo) vs. adult (9 mo) male Fisher-344 × Brown Norway rats would have insulin resistance for Akt2 Thr308 phosphorylation (pAkt2Thr308), AS160 phosphorylation Thr642 (pAS160Thr642), and atypical PKC (aPKCζ/λ) activity corresponding in magnitude to the extent of insulin resistance for [3H]-2-deoxyglucose (2-DG) uptake. Epitrochlearis insulin-stimulated 2-DG uptake above basal values was unaltered by age, and epitrochlearis pAkt2Thr308, pAS160Thr642, and aPKCζ/λ activity were not significantly different in adult vs. old rats. Conversely, insulin-stimulated 2-DG uptake by the soleus of old vs. adult rats was reduced with 1.2 nM (42%) and 30 nM (28%) insulin concomitant with an age-related decline in pAkt2Thr308 of the insulin-stimulated soleus. There were no age effects on pAS160Thr642 or aPKCζ/λ activity or abundance of Akt2, AS160, GLUT4 or Appl1 protein in either muscle. The results suggest the possibility that an age-related decline in pAkt2Thr308, acting by a mechanism other than reduced pAS160Thr642, may play a role in the insulin resistance in the soleus of old rats. Skeletal muscle insulin resistance in old age is distinctive compared with other insulin-resistant rodent models that are not selective for greater insulin resistance in the soleus vs. the epitrochlearis.

scholarly journals Genomic predictors of testosterone levels are associated with muscle fiber size and strength

2021 ◽  
Author(s):  
João Paulo L. F. Guilherme ◽  
Ekaterina A. Semenova ◽  
Oleg V. Borisov ◽  
Andrey K. Larin ◽  
Ethan Moreland ◽  
...  
Keyword(s):  
Muscle Fiber ◽  
Handgrip Strength ◽  
Muscle Fibers ◽  
Fat Free Mass ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Testosterone Levels ◽  
Fiber Size ◽  
Fast Twitch Muscle ◽  
Fast Twitch

Abstract Purpose Circulating testosterone levels are a heritable trait with anabolic properties in various tissues, including skeletal muscle. So far, hundreds of single nucleotide polymorphisms (SNPs) associated with testosterone levels have been identified in nonathletic populations. The aim of the present study was to test the association of 822 testosterone-increasing SNPs with muscle-related traits (muscle fiber size, fat-free mass and handgrip strength) and to validate the identified SNPs in independent cohorts of strength and power athletes. Methods One hundred and forty-eight physically active individuals (47 females, 101 males) were assessed for cross-sectional area (CSA) of fast-twitch muscle fibers. Significant SNPs were further assessed for fat-free mass and handgrip strength in > 354,000 participants from the UK Biobank cohort. The validation cohorts included Russian elite athletes. Results From an initial panel of 822 SNPs, we identified five testosterone-increasing alleles (DOCK3 rs77031559 G, ESR1 rs190930099 G, GLIS3 rs34706136 TG, GRAMD1B rs850294 T, TRAIP rs62260729 C) nominally associated (P < 0.05) with CSA of fast-twitch muscle fibers, fat-free mass and handgrip strength. Based on these five SNPs, the number of testosterone-increasing alleles was positively associated with testosterone levels in male athletes (P = 0.048) and greater strength performance in weightlifters (P = 0.017). Moreover, the proportion of participants with ≥ 2 testosterone-increasing alleles was higher in power athletes compared to controls (68.9 vs. 55.6%; P = 0.012). Conclusion Testosterone-related SNPs are associated with muscle fiber size, fat-free mass and strength, which combined can partially contribute to a greater predisposition to strength/power sports.

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