[Effect of Cisatracurium to Intensify Diaphragmatic Atrophy in Mechanically Ventilated Rats]

Area of Science:

• Physiology
• Cell Biology
• Pharmacology

Background:

• Mechanical ventilation (MV) is crucial for respiratory support but can lead to diaphragm atrophy.
• Understanding the molecular mechanisms underlying MV-induced diaphragm atrophy is essential for developing therapeutic strategies.

Purpose of the Study:

• To investigate the role of cisatracurium in diaphragm atrophy in mechanically ventilated rats.
• To elucidate the underlying mechanism involving the autophagy-lysosome pathway and mitophagy.

Main Methods:

• Adult male Sprague-Dawley rats were divided into control, MV, MV+cisatracurium, MV+chloroquine, and MV+cisatracurium+chloroquine groups.
• Diaphragm muscle specimens were analyzed for fiber cross-sectional area (CSA), mitophagy markers (TOM20, LC3), and atrophy markers (MAFbx, MURF-1) using HE staining, immunofluorescence, and Western blot.

Main Results:

• Mechanical ventilation induced diaphragm atrophy, evidenced by decreased CSA and increased expression of atrophy and mitophagy-related proteins (MURF-1, MAFbx, PINK1, Parkin, LC3).
• Cisatracurium administration exacerbated diaphragm atrophy and mitophagy.
• Chloroquine treatment partially reversed the effects of cisatracurium, suggesting a role for the autophagy-lysosome pathway.

Conclusions:

• Mechanical ventilation for 24 hours causes significant diaphragm atrophy in rats.
• Cisatracurium may aggravate this atrophy through PINK1/Parkin-mediated mitophagy via the autophagy-lysosome pathway.
• Chloroquine can reduce cisatracurium-induced diaphragmatic atrophy by inhibiting the autophagy-lysosome pathway.