scholarly journals COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients

2021 ◽  
Vol 8 (1) ◽  
pp. e001052
Author(s):  
Zhonghua Shi ◽  
Sylvia J P Bogaards ◽  
Stefan Conijn ◽  
Yeszamin Onderwater ◽  
Pedro Espinosa ◽  
...  

IntroductionThe diaphragm is the main muscle of inspiration, and its dysfunction contributes to adverse clinical outcomes in critically ill patients. We recently reported the infiltration of SARS-CoV-2, and the development of fibrosis, in the diaphragm of critically ill patients with COVID-19. In the current study, we aimed to characterise myofiber structure in the diaphragm of critically ill patients with COVID-19.MethodsDiaphragm muscle specimens were collected during autopsy from patients who died of COVID-19 in three academic medical centres in the Netherlands in April and May 2020 (n=27). We studied diaphragm myofiber gene expression and structure and compared the findings obtained to those of deceased critically ill patients without COVID-19 (n=10).ResultsMyofibers of critically ill patients with COVID-19 showed on average larger cross-sectional area (slow-twitch myofibers: 2441±229 vs 1571±309 µm2; fast-twitch myofibers: 1966±209 vs 1225±222 µm2). Four critically ill patients with COVID-19 showed extremely large myofibers, which were splitting and contained many centralised nuclei. RNA-sequencing data revealed differentially expressed genes involved in muscle regeneration.ConclusionDiaphragm of critically ill patients with COVID-19 has distinct myopathic features compared with critically ill patients without COVID-19, which may contribute to the ongoing dyspnoea and fatigue in the patients surviving COVID-19 infection.

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Sophia van der Hoeven ◽  
◽  
Lorenzo Ball ◽  
Federico Constantino ◽  
David M. van Meenen ◽  
...  

Abstract Background Accumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the ‘Preventive Nebulization of Mucolytic Agents and Bronchodilating Drugs in Intubated and Ventilated Intensive Care Unit Patients trial’ (NEBULAE) was to compare the effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of secretions in endotracheal tubes in critically ill patients. Results In this single-center substudy of a national multicenter trial, patients were randomized to a strategy of routine nebulizations of acetylcysteine with salbutamol every 6 h until end of invasive ventilation, or to a strategy with on-demand nebulizations of acetylcysteine or salbutamol applied on strict clinical indications only. The primary endpoint, the maximum reduction in cross-sectional area (CSA) of the endotracheal tube was assessed with high-resolution computed tomography. Endotracheal tubes were collected from 72 patients, 36 from patients randomized to the routine nebulization strategy and 36 of patients randomized to the on-demand nebulization strategy. The maximum cross-sectional area (CSA) of the endotracheal tube was median 12 [6 to 15]% in tubes obtained from patients in the routine nebulization group, not different from median 9 [6 to 14]% in tubes obtained from patients in the on-demand nebulization group (P = 0.33). Conclusion In adult critically ill patients under invasive ventilation, routine nebulization of mucolytics and bronchodilators did not affect accumulation of airway secretions in the endotracheal tube. Trial registration Clinicaltrials.gov Identifier: NCT02159196


2019 ◽  
Vol 47 (5) ◽  
pp. 423-434 ◽  
Author(s):  
Luke M Weinel ◽  
Matthew J Summers ◽  
Lee-Anne Chapple

Muscle wasting in the intensive care unit (ICU) is common and may impair functional recovery. Ultrasonography (US) presents a modern solution to quantify skeletal muscle size and monitor muscle wasting. However, no standardised methodology for the conduct of ultrasound-derived quadriceps muscle layer thickness or cross-sectional area in this population exists. The aim of this study was to compare methodologies reported for the measurement of quadriceps muscle layer thickness (MLT) and cross-sectional area (CSA) using US in critically ill patients. Databases PubMed, Ovid, Embase, and CINAHL were searched for original research publications that reported US-derived quadriceps MLT and/or CSA conducted in critically ill adult patients. Data were extracted from eligible studies on parameters relating to US measurement including anatomical location, patient positioning, operator technique and image analysis. It was identified that there was a clear lack of reported detail and substantial differences in the reported methodology used for all parameters. A standardised protocol and minimum reporting standards for US-derived measurement of quadriceps muscle size in ICU is required to allow for consistent measurement techniques and hence interpretation of results.


2016 ◽  
Vol 66 (1) ◽  
pp. 132-137
Author(s):  
Ivana Božičković ◽  
Duško Vitorović ◽  
Miloš Blagojević ◽  
Ivana Nešić ◽  
Slavoljub Jović ◽  
...  

AbstractThe aim of this paper was to investigate the differences in morphometric characteristics and histological structure of m. semitendinosus, between gilts and barrows of German Landrace breed at the end of the fattening period. Morphometric characteristics (weight, length, diameter and cross sectional area) of m. semitendinosus were not significantly different, while gender as a factor influenced the histological properties of this muscle. A very high statistical difference (p<0.01) in the total number of muscle fibers in m. semitendinosus was determined, with gilts having a higher total fiber number. The cross sectional area of fast twitch oxidative (FTO) fibers was significantly higher (p<0.05) in barrows. Gender did not affect the distribution of different fiber types: in both gender, the most present fiber types (48-52 %) were fast twitch glycolitic (FTG), FTO fibers represented 27-30 % of the total fiber number, while slow twitch oxidative fibers (STO) were the least represented (≈ 20 %).


1992 ◽  
Vol 73 (2) ◽  
pp. S51-S57 ◽  
Author(s):  
Y. Ohira ◽  
B. Jiang ◽  
R. R. Roy ◽  
V. Oganov ◽  
E. Ilyina-Kakueva ◽  
...  

Morphological and enzymatic responses in fibers expressing fast, slow, or both types of myosin heavy chain (MHC) were studied in rats after 14 days of spaceflight (COSMOS 2044) or hindlimb suspension. Although the percentage of slow-twitch fibers was unchanged, a higher percentage of fibers that expressed both slow and fast MHC was observed in flight and suspended rats than in synchronous ground-based controls. The soleus was 25 and 34% smaller than control after 14 days of flight and suspension, with the reduction in fiber cross-sectional area (CSA) being greater in slow- than in fast-twitch fibers in both experimental groups. The activities of succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPD) were not significantly affected by flight or suspension. The total SDH activity (i.e., SDH activity x CSA) decreased significantly in the slow-twitch fibers of the flight and the fast-twitch fibers of the suspended rats, in large part due to fiber atrophy. A shift in MHC expression in 14 and 9% of the fibers in flight and suspended rats occurred without a change in myosin adenosinetriphosphatase activity. The SDH and GPD activities of the fibers that expressed both slow and fast MHC were slightly higher than the slow-twitch fibers and slightly lower than the fast-twitch fibers. These data indicate that events were initiated within 14 days of spaceflight or suspension that began to reconfigure the protein profiles of 9–14% of the slow-twitch fibers from typical slow-twitch toward those of fast-twitch fibers, while all fibers were dramatically losing total protein.(ABSTRACT TRUNCATED AT 250 WORDS)


1987 ◽  
Vol 63 (3) ◽  
pp. 1076-1082 ◽  
Author(s):  
G. C. Sieck ◽  
R. D. Sacks ◽  
C. E. Blanco

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.


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 ◽  
...  

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.


1990 ◽  
Vol 64 (4) ◽  
pp. 1261-1269 ◽  
Author(s):  
A. R. Luff ◽  
K. Torkko

1. It was the aim of this study to determine the effect that regenerating motor axons would have on enlarged or sprouted motor units that had been established for a relatively long time. 2. The fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus were partially denervated by unilateral section of the L7 ventral root in 12-wk-old kittens. After 200+ days single motor units were isolated, and their isometric contractile properties were determined. FDL units were also tested for their resistance to fatigue and categorized as fast-twitch-fatigable (FF), fast-twitch-fatigue-resistant (FR), and slow-twitch-fatigue-resistant (S). 3. It had been established previously that regenerating motor axons via L7 returned to the experimental muscles by approximately 100 days. Therefore from 100 to 200 days it was assumed that the sprouted units would be in competition with the regenerating axons. The extent of the original denervations was variable and was estimated from the contralateral side. In soleus most denervations ranged from 83 to 99%; in FDL, from 37 to 81%. 4. In both soleus and FDL there was no evidence that the motor units had sprouted to any less extent than found previously. Within some soleus muscles the largest motor units were developing substantially more force than was expected. However, determination of mean fiber cross-sectional area from muscles frozen, sectioned, and prepared for histochemical analysis showed that this was attributable to increased mean cross-sectional area of the type I fibers.(ABSTRACT TRUNCATED AT 250 WORDS)


Thorax ◽  
2011 ◽  
Vol 66 (Suppl 4) ◽  
pp. A95-A95
Author(s):  
B. Connolly ◽  
Z. Puthucheary ◽  
H. Montgomery ◽  
J. Moxham ◽  
N. Hart

1986 ◽  
Vol 60 (4) ◽  
pp. 1284-1292 ◽  
Author(s):  
G. C. Sieck ◽  
R. D. Sacks ◽  
C. E. Blanco ◽  
V. R. Edgerton

The succinate dehydrogenase (SDH) activity and cross-sectional area of individual muscle fibers in the cat diaphragm were quantified using a computerized image-processing system. The population distributions of fiber-SDH activities and cross-sectional areas showed considerable range within each diaphragm. Despite an overlap in the distribution of SDH activities between fast-twitch (i.e., those staining darkly for myosin ATPase) and slow-twitch (i.e., those staining lightly for myosin ATPase) fibers, differences between the two populations of fibers were observed. Fast-twitch fibers generally had lower SDH activities and greater cross-sectional areas than slow-twitch fibers. However, the range of SDH activities and cross-sectional areas of fast-twitch fibers was much greater than in slow-twitch fibers. The population distributions of SDH activities and cross-sectional areas of both fast- and slow-twitch fibers were unimodal. The unimodal distribution of SDH activities in fast-twitch fibers suggested that these fibers could not be clearly subdivided into two groups based on differences in their oxidative capacity (i.e., high- and low-oxidative fibers). These results were discussed in the context of the classification of fast-twitch glycolytic and fast-twitch oxidative-glycolytic fibers using qualitative histochemistry. In addition, the functional significance of the unimodal distribution of oxidative capacities in fast-twitch fibers was discussed in relation to the distribution of fatigue properties in fast-twitch motor units. A significant negative correlation between cross-sectional area and SDH activity in both fast- and slow-twitch fibers was also observed. The importance of this negative correlation in relationship to the diffusion of energy substrates for oxidative metabolism was discussed.


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