HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

Late Ventilator-Induced Diaphragmatic Dysfunction After Extubation

Abstract : Objectives: Mechanical ventilation is associated with primary diaphragmatic dysfunction, also termed ventilator-induced diaphragmatic dysfunction. Studies evaluating diaphragmatic function recovery after extubation are lacking. We evaluated early and late recoveries from ventilator-induced diaphragmatic dysfunction in a mouse model. Design: Experimental randomized study. Setting: Research laboratory. Subjects: C57/BL6 mice. Interventions: Six groups of C57/BL6 mice. Mice were ventilated for 6 hours and then euthanatized immediately (n = 18), or 1 (n = 18) or 10 days after extubation with (n = 5) and without S107 (n = 16) treatment. Mice euthanatized immediately after 6 hours of anesthesia (n = 15) or after 6 hours of anesthesia and 10 days of recovery (n = 5) served as controls. Measurements and Main Results: For each group, diaphragm force production, posttranslational modification of ryanodine receptor, oxidative stress, proteolysis, and cross-sectional areas were evaluated. After 6 hours of mechanical ventilation, diaphragm force production was decreased by 25–30%, restored to the control levels 1 day after extubation, and secondarily decreased by 20% 10 days after extubation compared with controls. Ryanodine receptor was protein kinase A-hyperphosphorylated, S-nitrosylated, oxidized, and depleted of its stabilizing subunit calstabin-1 6 hours after the onset of the mechanical ventilation, 1 and 10 days after extubation. Post extubation treatment with S107, a Rycal drug that stabilizes the ryanodine complex, did reverse the loss of diaphragmatic force associated with mechanical ventilation. Total protein oxidation was restored to the control levels 1 day after extubation. Markers of proteolysis including calpain 1 and calpain 2 remained activated 10 days after extubation without significant changes in cross-sectional areas. Conclusions: We report that mechanical ventilation is associated with a late diaphragmatic dysfunction related to a structural alteration of the ryanodine complex that is reversed with the S107 treatment.
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-02956989
Contributor : Dominique Mornet Connect in order to contact the contributor
Submitted on : Wednesday, October 14, 2020 - 9:19:53 AM
Last modification on : Wednesday, November 3, 2021 - 8:07:20 AM

File

2020 Dridi et al., Late.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Haikel Dridi, Boris Jung, Mohamad Yehya, Aurelien Daurat, Steven Reiken, et al.. Late Ventilator-Induced Diaphragmatic Dysfunction After Extubation. Critical Care Medicine, Lippincott, Williams & Wilkins, In press, ⟨10.1097/CCM.0000000000004569⟩. ⟨hal-02956989⟩

Share

Metrics

Record views

64

Files downloads

102