Ruxolitinib: A new hope for ventilator‐induced diaphragm dysfunction

Aim Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator‐induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STA...

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Published in:Acta Physiologica 2024-05, Vol.240 (5), p.e14128-n/a
Main Authors: Addinsall, Alex B., Cacciani, Nicola, Moruzzi, Noah, Akkad, Hazem, Maestri, Alice, Berggren, Per‐Olof, Widegren, Anna, Bergquist, Jonas, Tchkonia, Tamara, Kirkland, James L., Larsson, Lars
Format: Article
Language:English
Subjects:
Animals
critical care
Diaphragm
Diaphragm - drug effects
Diaphragm - metabolism
Diaphragm - physiopathology
Electron transport
Janus kinase
Kinases
Male
Mass spectroscopy
Mechanical ventilation
Medicin och hälsovetenskap
Mitochondria
Myosin
Nitriles - pharmacology
Oxygen consumption
post-translational modification
Pyrazoles - pharmacology
Pyrazoles - therapeutic use
Pyrimidines - pharmacology
Pyrimidines - therapeutic use
Rats
Rats, Sprague-Dawley
Respiration, Artificial - adverse effects
STAT3
Stat3 protein
Survival
Ventilators
VIDD
Weaning
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Summary:Aim Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator‐induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is implicated in VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential of Ruxolitinib, an FDA approved JAK1/2 inhibitor (JI) for the treatment of VIDD. Methods Rats were subjected to 5 days controlled MV (CMV) with and without daily Ruxolitinib gavage. Muscle fiber size and function were assessed. RNAseq, mitochondrial morphology, respirometry, and mass spectrometry were determined. Results CMV significantly reduced diaphragm size and specific force by 45% (p 
ISSN:1748-1708
1748-1716
1748-1716
DOI:10.1111/apha.14128