Interactive effects of corticosteroid and mechanical ventilation on diaphragm muscle function

Area of Science:

• Physiology
• Pharmacology
• Critical Care Medicine

Background:

• Diaphragm dysfunction is a significant concern in mechanically ventilated patients.
• The impact of corticosteroids, like methylprednisolone, on diaphragm function during mechanical ventilation is not fully understood.
• Understanding these interactions is crucial for optimizing patient care and ventilator strategies.

Purpose of the Study:

• To investigate the interactive effects of methylprednisolone (MP) with controlled mechanical ventilation (CMV) and assisted mechanical ventilation (AMV) on diaphragm function.
• To determine if MP exacerbates or mitigates ventilation-induced diaphragm injury.
• To elucidate the molecular mechanisms underlying these interactions.

Main Methods:

• Sedated rabbits were subjected to 2 days of CMV, AMV, or spontaneous breathing (SB) with either intravenous methylprednisolone (60 mg/kg/day) or saline.
• Diaphragm muscle function (maximal tetanic tension, P(o)), myofibrillar ultrastructure, αII-spectrin, insulin-like growth factor-1 (IGF-1), and MAF-box mRNA were assessed.
• A control group receiving no intervention was included.

Main Results:

• CMV significantly reduced P(o), but co-administration with MP did not further decrease it.
• AMV alone did not impair P(o) compared to SB and controls.
• Combined MP with AMV or SB substantially decreased P(o) and induced myofibrillar disruption.
• MP plus CMV, MP plus AMV, or MP plus SB increased αII-spectrin, decreased IGF-1, and increased MAF-box mRNA, indicating muscle injury and atrophy signaling.

Conclusions:

• Acute, high-dose methylprednisolone can impair diaphragm function, particularly when combined with assisted mechanical ventilation.
• Methylprednisolone did not exacerbate CMV-induced diaphragm dysfunction in this model.
• Diaphragm dysfunction induced by MP depends on the mode of mechanical ventilation, highlighting the importance of ventilator settings in corticosteroid-treated patients.