Age related differences in diaphragm muscle fiber response to mid/long term controlled mechanical ventilation

Controlled mechanical ventilation (CMV) is known to result in rapid and severe diaphragmatic dysfunction, but the recovery response of the diaphragm to normal function after CMV is unknown. Therefore, we examined the time course of diaphragm function recovery in an animal model of CMV. Healthy rats were submitted to CMV for 24–27 h ( n = 16), or to 24-h CMV followed by either 1 h (CMV + 1 h SB, n = 9), 2 h (CMV + 2 h SB, n = 9), 3 h (CMV + 3 h SB, n = 9), or 4–7 h (CMV + 4–7 h SB, n = 9) of spontaneous breathing (SB). At the end of the experiment, the diaphragm muscle was excised for functional and biochemical analysis. The in vitro diaphragm force was significantly improved in the CMV + 3 h SB and CMV + 4–7 h SB groups compared with CMV (maximal tetanic force: +27%, P < 0.05, and +59%, P < 0.001, respectively). This was associated with an increase in the type IIx/b fiber dimensions ( P < 0.05). Neutrophil influx was increased in the CMV + 4–7 h SB group ( P < 0.05), while macrophage numbers remained unchanged. Markers of protein synthesis (phosphorylated Akt and eukaryotic initiation factor 4E binding protein 1) were significantly increased (±40%, P < 0.001, and ±52%, P < 0.01, respectively) in the CMV + 3 h SB and CMV + 4–7 h SB groups and were positively correlated with diaphragm force ( P < 0.05). Finally, also the maximal specific force generation of skinned single diaphragm fibers was increased in the CMV + 4–7 h SB group compared with CMV (+45%, P < 0.05). In rats, reloading the diaphragm for 3 h after CMV is sufficient to improve diaphragm function, while complete recovery occurs after longer periods of reloading. Enhanced muscle fiber dimensions, increased protein synthesis, and improved intrinsic contractile properties of diaphragm muscle fibers may have contributed to diaphragm function recovery.

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Dose-Response Of Methylprednisolone Administration On Rabbits Diaphragm Muscle Force Generating Capacity During Controlled Mechanical Ventilation

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2706 ◽

2012 ◽

Author(s):

Ercheng Zhu ◽

Liwei Fang ◽

Catherine Sassoon

Keyword(s):

Mechanical Ventilation ◽

Dose Response ◽

Muscle Force ◽

Diaphragm Muscle ◽

Generating Capacity ◽

Controlled Mechanical Ventilation

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No decrease in myonuclear number after long-term denervation in mature mice

AJP Cell Physiology ◽

10.1152/ajpcell.00025.2002 ◽

2002 ◽

Vol 283 (2) ◽

pp. C484-C488 ◽

Cited By ~ 33

Author(s):

K.-I. Wada ◽

H. Takahashi ◽

S. Katsuta ◽

H. Soya

Keyword(s):

Age Differences ◽

Muscle Fiber ◽

Age Difference ◽

Sectional Area ◽

Cross Sectional ◽

Age Related ◽

Muscle Fiber Atrophy ◽

Fiber Atrophy ◽

Young Mice

Age-related but not artificially induced muscle fiber atrophy has been shown to occur without any decrease in myonuclear number, although these results remain controversial. The present study was carried out to clarify whether age difference affects the degree of decrease in myonuclear number occurring with denervation-induced fiber atrophy. After denervation of 3-wk-old (young) and 4-mo-old (mature) mice, single myofibers were isolated from the plantaris muscles by alkali maceration, and their fiber cross-sectional area (CSA), myonuclear number, and cytoplasm-to-myonucleus (C/N) ratios were analyzed. Fiber CSA in both young and mature mice decreased with denervation. Myonuclear number decreased in young mice 5 and 10 days after denervation but was unchanged in mature mice 10 and 120 days after denervation. C/N ratio decreased in mature mice but was unchanged in denervated young mice. These results suggest that age differences affect the degree of decrease of myonuclear number with denervation and that fiber cytoplasmic atrophy may occur without decrease in myonuclear number.

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Long-term effects of clenbuterol on diaphragm morphology and contractile properties in emphysematous hamsters

Journal of Applied Physiology ◽

10.1152/jappl.1998.85.1.215 ◽

1998 ◽

Vol 85 (1) ◽

pp. 215-222 ◽

Cited By ~ 19

Author(s):

H. F. M. Van Der Heijden ◽

P. N. R Dekhuijzen ◽

H. Folgering ◽

L. A. Ginsel ◽

C. L. A. Van Herwaarden

Keyword(s):

Muscle Fiber ◽

Contractile Properties ◽

Diaphragm Muscle ◽

Muscle Fiber Types ◽

Type I ◽

Fiber Types ◽

Force Frequency ◽

Long Term Effects ◽

Muscle Weight

The aim of the present study was to investigate the effect of chronic long-term clenbuterol treatment (1 mg/kg subcutaneously twice a day for 12 wk) on diaphragm morphology and function in emphysematous (EH) and normal hamsters (NH). Clenbuterol increased body weight, diaphragm weight, and skeletal muscle weight in both EH and NH to a similar extent. In the diaphragm, clenbuterol significantly increased myosin heavy chain type I, IIa, and IIx muscle fiber cross-sectional areas by ∼35–55% in both EH and NH. This response to clenbuterol treatment was not significantly different between EH and NH diaphragm. In EH, twitch force (Pt), maximal tetanic force, and force-frequency curve were significantly reduced compared with NH. In EH, clenbuterol increased Pt by ∼10%, restoring Pt to NH level. A similar improvement was observed in the force-frequency characteristics. Clenbuterol did not alter contractile properties in NH. In conclusion, long-term clenbuterol treatment resulted in an increased size of all diaphragm muscle fiber types in both NH and EH. Clenbuterol completely abolished the reduced force generation induced by emphysema.

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Multi-omics reveals age-related differences in the diaphragm response to mechanical ventilation: a pilot study

Skeletal Muscle ◽

10.1186/s13395-021-00267-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Qiong Lyu ◽

Ya Wen ◽

Xiang Zhang ◽

Alex B. Addinsall ◽

Nicola Cacciani ◽

...

Keyword(s):

Mechanical Ventilation ◽

Viral Infection ◽

Old Age ◽

Inflammatory Responses ◽

Inflammatory Factors ◽

Icu Patients ◽

Age Related ◽

Life Saving ◽

Old Rats

Abstract Background Old age is associated with a significantly increased mortality in COVID-19 patients exposed to long-term controlled mechanical ventilation (CMV) and suggested to be due to the hyperinflammatory response associated with the viral infection. However, our understanding of age-related differences in the response to CMV in the absence of a viral infection remains insufficient. Methods Young (7–8 months) and old (28–32 months) F344 BN hybrid rats were exposed to the ICU condition for 5 days, i.e., complete immobilization, mechanical ventilation, and extensive monitoring. Transcriptomic (RNA-Seq) and proteomics (Proximity Extension Assay) analyses of the diaphragm and proteomics analysis of plasma were conducted to investigate the molecular differences between young and old rats exposed to the ICU condition. Results According to multi-omics analyses, significant differences were observed in the diaphragm between young and old rats in response to 5 days CMV and immobilization. In young rats, metabolic pathways were primarily downregulated in response to immobilization (post-synaptic blockade of neuromuscular transmission). In old rats, on the other hand, dramatic immune and inflammatory responses were observed, i.e., an upregulation of specific related pathways such as “IL-17 signaling pathway”, along with a higher level of inflammatory factors and cytokine/chemokine in plasma. Conclusions The dramatically increased mortality in old ICU patients with COVID-19-associated hyperinflammation and cytokine storm need not only reflect the viral infection but may also be associated with the ventilator induced diaphragm dysfunction (VIDD) and hyperinflammatory responses induced by long-term CMV per se. Although mechanical ventilation is a life-saving intervention in COVID-19 ICU patients, CMV should be cautiously used especially in old age and other means of respiratory support may be considered, such as negative pressure ventilation.

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Effects of controlled and pressure support mechanical ventilation on rat diaphragm muscle

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502012000200003 ◽

2012 ◽

Vol 27 (2) ◽

pp. 109-116 ◽

Cited By ~ 1

Author(s):

André de Sá Braga Oliveira ◽

Lívia Bandeira Costa ◽

Thiago de Oliveira Assis ◽

Diógenes Luís da Mota ◽

Eduardo Ériko Tenório de França ◽

...

Keyword(s):

Mechanical Ventilation ◽

Pressure Support ◽

Muscular Atrophy ◽

Diaphragm Muscle ◽

Control Group ◽

Cross Sectional ◽

Significant Difference ◽

Controlled Mechanical Ventilation ◽

To Receive ◽

Pressure Controlled

PURPOSE: The objective of this study was to analyze the effects of Pressure Controlled Ventilation mode (PCV-C) and PSV mode in diaphragm muscle of rats. METHODS: Wistar rats (n=18) were randomly assigned to the control group or to receive 6 hours of PCV and PSV. After this period, animals were euthanized and their diaphragms were excised, frozen in liquid nitrogen and stored in at -80º C for further histomorphometric analysis. RESULTS: Results showed a 15% decrease in cross-sectional area of muscle fibers on the PCV-C group when compared to the control group (p<0.001) and by 10% when compared to the PSV group (p<0.05). Minor diameter was decreased in PCV-C group by 9% when compared with the control group (p<0.001) and by 6% when compared to the PSV group (p<0.05). When myonuclear area was analyzed, a 16% decrease was observed in the PCV-C group when compared to the PSV group (p<0.05). No significant difference between the groups was observed in myonuclear perimeter (p>0.05). CONCLUSION: Short-term controlled mechanical ventilation seems to lead to muscular atrophy in diaphragm fibers. The PSV mode may attenuate the effects of VIDD.

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