Figure 1

Mechanistic pathways implicated in the human studies of ventilator-induced diaphragmatic dysfunction in critically ill patients. Diaphragmatic inactivity induced by mechanical ventilation is associated with an increased generation of reactive oxygen species (ROS) and a downregulation of the Akt pathway. This leads to increased proteolysis in the diaphragm via activation of the caspase, calpain, ubiquitin-proteasome, and lysosomal-autophagic pathways. In addition, downregulation of the Akt pathway also inhibits protein synthesis (dotted line). Collectively, all of the above contribute to atrophy and injury of diaphragmatic muscle fibers, resulting in functional impairment of the diaphragm. Akt-P, phosphorylated (activated) form of protein kinase B.