JAP-00104-2006.R1

Redox status of the unloaded diaphragm 1 Oxidative stress is an important mediator of diaphragm muscle atrophy and contractile dysfunction during prolonged periods of controlled mechanical ventilation (MV). To date, specific details related to the impact of MV on diaphragmatic redox status remain unknown. To fill this void, we tested the hypothesis that MV-induced diaphragmatic oxidative stress is the consequence of both an elevation in intracellular oxidant production in conjunction with a decrease in the antioxidant buffering capacity. Adult rats were assigned to one of two experimental groups: 1) control; or 2) 12 hours of MV. Compared to controls, diaphragms from MV animals demonstrated increased oxidant production, diminished total antioxidant capacity (TAC), and decreased glutathione levels. Heme oxygenase-1 (HO-1) mRNA and protein levels increased (+23.0 and +5.1 fold, respectively) following MV. Thioredoxin reductase-1 and manganese superoxide dismutase mRNA levels were also increased in the diaphrag