The Journal of Practical Medicine >

2024 , Vol. 40 >Issue 18: 2537 - 2543

DOI: https://doi.org/10.3969/j.issn.1006-5725.2024.18.005

Basic Research

Effects of mechanical ventilation on diaphragmatic neuromuscular junction in rats

  • Rui TU ,
  • Jumei ZHANG ,
  • Fasheng GUAN ,
  • Li. LIU
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  • Department of Anesthesia，the Affiliated Hospital of Southwest Medical University，Luzhou 646000，China

Received date: 2024-03-15

  Online published: 2024-09-30

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Abstract

Objective To explore the effects of mechanical ventilation and mechanical ventilation combined with phrenic nerve electrical stimulation on the morphology of the phrenic nerve-diaphragm neuromuscular junction in rats. Methods The rats were divided into a control group （CON group， n = 6）； an 18-hour mechanical ventilation group （MV group， n = 6）； an 18-hour ventilation combined with sham electrical stimulation group （S-MS group， n = 6）； and an 18-hour ventilation combined with electrical stimulation group （MS group， n = 6）， in which the diaphragm contraction force was detected through the biological signal acquisition system， the stimulation frequency-contraction curve was fitted， and the muscle fatigue index was calculated. The muscle fiber cross-sectional area （CSA） of the diaphragm specimen was observed through HE staining； the endplate membrane area of the neuromuscular junction （NMJ） was observed through immunohistochemistry （IHC） staining of the diaphragm combined with laser confocal technology. Results As compared with the CON group， the contractility of isolated diaphragm muscles in the MV group and S-MS group decreased； the fatigue resistance of isolated diaphragm， as compared with the CON group （0.686 8 ± 0.049 42）， decreased in the MV group （0.360 3 ± 0.066 89） and the S-MS group （0.367 9 ± 0.034 94）， with a greater decline in the MS group （0.536 2 ± 0.054 38）； as compared with the CON group ［674.3（523.9，863.6）］， diaphragm CSA was reduced in the MV group ［374.5（293.3，522.7）］ and S-MS group ［392.8（309.5，542.6）］， with a relatively lower reduction in the MS group ［592.7（425.1，820.0）］； as compared with the CON group ［393.7（293.5，471.3）］， the diaphragm endplate membrane area decreased in the MV group ［289.7（227.0，354.2）］ and S-MS group ［243.1（190.8，331.7）］， with a lower degree of reduction in the MS group ［331.0（262.8，413.7）. Conclusions Mechanical ventilation causes diaphragm dysfunction in rats and decreases the endplate membrane area of the diaphragm NMJ. Bilateral phrenic nerve electrical stimulation for 10 min/h can improve diaphragm dysfunction and changes in the endplate membrane area of the diaphragm NMJ caused by mechanical ventilation.

Key words： mechanical ventilation; mechanical ventilation-related diaphragm dysfunction; neuromuscular junction; diaphragm

Cite this article

Rui TU , Jumei ZHANG , Fasheng GUAN , Li. LIU . Effects of mechanical ventilation on diaphragmatic neuromuscular junction in rats[J]. The Journal of Practical Medicine, 2024 , 40(18) : 2537 -2543 . DOI: 10.3969/j.issn.1006-5725.2024.18.005

References

1 LEVINE S， NGUYEN T， TAYLOR N， et al. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans［J］. N Engl J Med， 2008，358（13）： 1327-1335. doi:10.1056/nejmoa070447
2 HYATT H W， OZDEMIR M， BOMKAMP M P， et al. Activation of Calpain Contributes to Mechanical Ventilation-Induced Depression of Protein Synthesis in Diaphragm Muscle［J］. Cells， 2022，11（6）：1028.
3 JABER S， PETROF B J， JUNG B， et al. Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans［J］. Am J Respir Crit Care Med， 2011，183（3）： 364-371. doi:10.1164/rccm.201004-0670oc
4 YE X， LIU Z， MA Y， et al. A Novel Normalized Cross-Correlation Speckle-Tracking Ultrasound Algorithm for the Evaluation of Diaphragm Deformation［J］. Front Med （Lausanne）， 2021，8： 612933. doi:10.3389/fmed.2021.612933
5 PETROF B J， HUSSAIN S N. Ventilator-induced diaphragmatic dysfunction： what have we learned？［J］. Curr Opin Crit Care， 2016，22（1）： 67-72.
6 DRES M， DUBé B P， MAYAUX J， et al. Coexistence and Impact of Limb Muscle and Diaphragm Weakness at Time of Liberation from Mechanical Ventilation in Medical Intensive Care Unit Patients［J］. Am J Respir Crit Care Med， 2017，195（1）： 57-66. doi:10.1164/rccm.201602-0367oc
7 ZHANG J， FENG J， JIA J， et al. Research progress on the pathogenesis and treatment of ventilator-induced diaphragm dysfunction［J］. Heliyon， 2023，9（11）： e22317. doi:10.1016/j.heliyon.2023.e22317
8 CHENG L， SAMI A， GHOSH B， et al. LAR inhibitory peptide promotes recovery of diaphragm function and multiple forms of respiratory neural circuit plasticity after cervical spinal cord injury［J］. Neurobiol Dis， 2021，147： 105153. doi:10.1016/j.nbd.2020.105153
9 WENZEL C， SPASSOV S G， LENGERER J， et al. Electromagnetic stimulation of the phrenic nerve preserves diaphragm muscle strength during mechanical ventilation in a rat model［J］. Eur J Anaesthesiol， 2022，39（1）： 81-82. doi:10.1097/eja.0000000000001590
10 GUO X， SMITH V， JACKSON M， et al. A Human-Based Functional NMJ System for Personalized ALS Modeling and Drug Testing［J］. Adv Ther （Weinh）， 2020，3（11）：2000133. doi:10.1002/adtp.202000133
11 CHIBALIN A V， BENZIANE B， ZAKYRJANOVA G F， et al. Early endplate remodeling and skeletal muscle signaling events following rat hindlimb suspension［J］. J Cell Physiol， 2018，233（10）： 6329-6336.
12 LEE Y I， CACCIANI N， WEN Y， et al. Direct electrical stimulation impacts on neuromuscular junction morphology on both stimulated and unstimulated contralateral soleus［J］. J Cachexia Sarcopenia Muscle， 2023，14（3）： 1533-1545.
13 SMUDER A J， SOLLANEK K J， NELSON W B， et al. Crosstalk between autophagy and oxidative stress regulates proteolysis in the diaphragm during mechanical ventilation［J］. Free Radic Biol Med， 2018，115： 179-190.
14 TANG H， LEE M， BUDAK M T， et al. Intrinsic apoptosis in mechanically ventilated human diaphragm： linkage to a novel Fos/FoxO1/Stat3-Bim axis［J］. Faseb J， 2011，25（9）： 2921-2936. doi:10.1096/fj.11-183798
15 MICHEL-FLUTOT P， JESUS I， VANHEE V， et al. Effects of Chronic High-Frequency rTMS Protocol on Respiratory Neuroplasticity Following C2 Spinal Cord Hemisection in Rats［J］. Biology （Basel）， 2022，11（3）：473. doi:10.3390/biology11030473
16 WEAVER L， DAS A， SAFFARAN S， et al. Optimising respiratory support for early COVID-19 pneumonia： a computational modelling study［J］. Br J Anaesth， 2022，128（6）： 1052-1058. doi:10.1016/j.bja.2022.02.037
17 李明娟， 李学欣， 刘力. 短时间机械通气对脓毒症大鼠膈肌功能的影响［J］. 实用医学杂志， 2023，39（5）： 579-584，590. doi:10.3969/j.issn.1006-5725.2023.05.009
18 JONKMAN A H， FRENZEL T， MCCAUGHEY E J， et al. Breath-synchronized electrical stimulation of the expiratory muscles in mechanically ventilated patients： a randomized controlled feasibility study and pooled analysis［J］. Crit Care， 2020，24（1）： 628. doi:10.1186/s13054-020-03352-0
19 LIANG F， LI T， AZUELOS I， et al. Ventilator-induced diaphragmatic dysfunction in MDX mice［J］. Muscle Nerve， 2018，57（3）： 442-448. doi:10.1002/mus.25760
20 SCHELLEKENS W J， VAN HEES H W， VANEKER M，et al. Toll-like receptor 4 signaling in ventilator-induced diaphragm atrophy［J］. Anesthesiology， 2012，117（2）： 329-338.
21 DESCHENES M R， JUDELSON D A， KRAEMER W J， et al. Effects of resistance training on neuromuscular junction morphology［J］. Muscle Nerve， 2000，23（10）： 1576-1581.
22 MOLOTSKY E， LIU Y， LIEBERMAN A P， et al. Neuromuscular junction pathology is correlated with differential motor unit vulnerability in spinal and bulbar muscular atrophy［J］. Acta Neuropathol Commun， 2022，10（1）： 97. doi:10.1186/s40478-022-01402-y
23 伍松柏， 戴瑶， 何峻，等. 超声测量膈肌增厚分数联合膈肌位移在预测机械通气成功撤机中的价值［J］. 实用医学杂志， 2021，37（12）： 1592-1597.
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