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Dual-Mode Ventilation Promotes Diaphragm Function Recovery in Rats With Ventilator-Induced Diaphragmatic Dysfunction
Xiao-Zhuo Zheng1, Lei Wu2, Qi Chen3
1Department of Anesthesiology, Women and Children's Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, China.
Introduction:
Ventilator-induced diaphragmatic dysfunction (VIDD) is associated with diaphragm atrophy and decreased contractility, leading to difficult weaning. Respiratory muscle training could prevent diaphragmatic dysfunction. IGF-1 is correlated with the enhancement of muscle mass and strength. The aim of this study was to investigate the effect of dual-mode ventilation (DMV) on diaphragm function recovery in VIDD rats, and to explore the role of insulin-like growth factor-1 (IGF-1) as an underlying mechanism.
Methods:
Adult male Sprague-Dawley rats were used to establish the VIDD model and randomly divided into seven groups. Diaphragm morphology, myofiber cross-sectional area, diaphragm contractility, reactive oxygen species production, superoxide dismutase activity, IGF-1 expression and protein levels related to muscle differentiation and protein synthesis were examined. Adeno-associated virus transfection was used to downregulate IGF-1 expression. Overexpression of IGF-1 was performed by subcutaneous injection of rhIGF-1 to explore the possible mechanism.
Results:
DMV increased myofiber cross-sectional area, improved diaphragm contractility, reduced reactive oxygen species production, enhanced superoxide dismutase activity, and upregulated the expression of Myod, Myogenin, MyHC, and a-actinin. DMV also upregulated the protein level of IGF-1 in the diaphragm of VIDD rats. In vivo, IGF-1 knockdown aggravated diaphragmatic dysfunction, increased oxidative stress injury, reduced protein synthesis and muscle differentiation, and decreased p-protein kinase B (Akt)/AKT and p-mammalian target of rapamycin (mTOR)/mTOR expression, while overexpression of IGF-1 reversed these changes.
Conclusions:
DMV is beneficial for diaphragm function recovery. And IGF-1 plays an important role in DMV to enhance diaphragm mass and strength of VIDD rats, which may promote protein synthesis and muscle differentiation through activating Akt/mTOR signaling pathway.
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