ArticleRespiratory research2023
PEEP application during mechanical ventilation contributes to fibrosis in the diaphragm.
Article in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- The contribution of mechanical ventilation to critical illness-associated diaphragm dysfunction: a critical appraisal.Critical care (London, England) · 2026Review
- High PEEP Activates ITGB1, Inducing Diaphragm Fibrosis During Prolonged Mechanical Ventilation.Biomolecules · 2025Article
- Single-nucleus transcriptomic profiling of the diaphragm during mechanical ventilation.Scientific reports · 2024Article
- Association of diaphragmatic dysfunction with duration of mechanical ventilation in patients in the pediatric intensive care unit: a prospective cohort study.BMC pediatrics · 2024Article
- Suppression of Ventilation-Induced Diaphragm Fibrosis through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model.International journal of molecular sciences · 2024Article
- Diaphragm ultrasound in patients with prolonged weaning from mechanical ventilation.Quantitative imaging in medicine and surgery · 2024Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPositive end-expiratory airway pressure (PEEP) is a potent component of management for patients receiving mechanical ventilation (MV). However, PEEP may cause the development of diaphragm remodeling, making it difficult for patients to be weaned from MV. The current study aimed to explore the role of PEEP in VIDD.
methodsEighteen adult male New Zealand rabbits were divided into three groups at random: nonventilated animals (the CON group), animals with volume-assist/control mode without/ with PEEP 8 cmH
resultsThere was no difference among the three groups in arterial blood gas and the diaphragmatic excursion during the experiment. The tidal volume, respiratory rate and minute ventilation were similar in MV + PEEP group and MV group. Airway peak pressure in MV + PEEP group was significantly higher than that in MV group (p < 0.001), and mechanical power was significantly higher (p < 0.001). RNA-seq showed that genes associated with fibrosis were enriched in the MV + PEEP group. This results were further confirmed on mRNA expression. As shown by Masson's trichrome staining, there was more collagen fiber in the MV + PEEP group than that in the MV group (p = 0.001). Sirius red staining showed more positive staining of total collagen fibers and type I/III fibers in the MV + PEEP group (p = 0.001; p = 0.001). The western blot results also showed upregulation of collagen types 1A1, III, 6A1 and 6A2 in the MV + PEEP group compared to the MV group (p < 0.001, all). Moreover, the positive immunofluorescence of COL III in the MV + PEEP group was more intense (p = 0.003). Furthermore, the expression of TGF-β1, one of the most potent fibrogenic factors, was upregulated at both the mRNA and protein levels in the MV + PEEP group (mRNA: p = 0.03; protein: p = 0.04).
conclusionsWe demonstrated that PEEP application for 48 h in mechanically ventilated rabbits will cause collagen deposition and fibrosis in the diaphragm. Moreover, activation of the TGF-β1 signaling pathway and myofibroblast differentiation may be the potential mechanism of this diaphragmatic fibrosis. These findings might provide novel therapeutic targets for PEEP application-induced diaphragm dysfunction.
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