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The proteolytic response in the diaphragm is blunted during mechanical ventilation in critically ill patients
Position du problème et objectif(s) de l’étude
Mechanical ventilation (MV) during critical illness is associated with proteolysis and decreased protein synthesis, leading to ventilator-induced diaphragmatic dysfunction (VIDD) and intensive care unit - acquired weakness (ICU-AW). VIDD is associated with prolonged MV and weaning failure. In this study, we aimed to identify a differential modulation between the diaphragm and other muscles during MV.
Matériel et méthodes
Diaphragm and rectus abdominis muscle biopsies were obtained from 14 brain dead donors mechanically ventilated for at least 24 hours (ethical approval PFS17-008). We performed histological analysis, RNA sequencing and explored pathways showing significant differential expression using RT-qPCR and Western blot.
Résultats & Discussion
The proteolytic and myogenic pathways were downregulated, whereas the inflammatory and extracellular matrix pathways were upregulated in the diaphragm. We observed a lower transcription of FOXO1 (-59%), ubiquitin ligase Murf1 (-50%), calpain 3 and protein kinase GSk3b (-90%) in the diaphragm compared to rectus abdominis, whereas the CXCR-pi3k-akt pathway was upregulated. Myofiber cross-sectional areas were larger in the diaphragm than in rectus abdominis (2224-3934µm² vs 2154-2973µm², p=0.012).
Conclusion
In the diaphragm of brain donors mechanically ventilated for at least 24 hours, atrophic muscle pathways are downregulated compared to the rectus abdominis. These results question the impact of MV on the diaphragm in critical illness and highlight the differential pathophysiology between ICU-AW and VIDD.
Auteurs
Aurélie CAMPEANU (1) , Jules LOEB (1), Myriam LAMAMRI (1), Olivier LANGERON (2), Maud CHAPART (3), Stéphane VASSEUR (3), Jean-Michel CONSTANTIN (1), Bruno RIOU (1), Adrien BOUGLÉ (1), Catherine COIRAULT (3) - (1)Hôpital Pitié Salpêtrière, Paris, France, (2)Hôpital Cavale Blanche, Brest, France, (3)Institut De Myologie, Paris, France