Objective Ventilator Induced Diaphragmatic Dysfunction (VIDD) may contribute to weaning failure of adults on controlled mechanical ventilation (CMV). VIDD is characterized by decreased diaphragm force generation capacity and increased muscle atrophy. Akt and MAPKerk1/2 signaling pathways regulate muscle protein metabolism and cell proliferation. The acute consequences of ventilation on muscle signaling pathways in preterm diaphragms are unknown. We aim to compare total and phosphorylated Akt and MAPKerk1/2 levels in diaphragms after CMV or continuous positive airway pressure (CPAP).
We hypothesize that CMV depresses activation of the Akt and MAPKerk1/2 pathways compared to CPAP.
Methods 133 d lambs (term = 150 d) were delivered by caesarean section and randomized to CMV or CPAP. After euthanasia of lambs at 3 h, diaphragm tissue was collected. Akt and MAPK protein levels were measured by Western blot.
Results No change in phosphorylated Akt (p = 0.285) or total Akt (p = 0.338) levels. CMV depressed phosphorylated MAPKerk1 (p = 0.031) and total MAPKerk2 (p = 0.034) levels with a similar trend for decreased phosphorylated MAPKerk2 (p = 0.07) and total MAPKerk1 (p = 0.065) levels in the CMV group.
Conclusions Decreased activation of MAPKerk1/2 in the CMV group may reflect a negative effect of CMV on transcription and impairment of muscle growth and fiber synthesis. The use of CMV in newborn lambs may increased risk of muscle atrophy and subsequent VIDD.
Supported by: WIRF, Fisher & Paykel Healthcare; Viertel Senior Medical Research Fellowship (JJP)