Mechanical ventilation promotes redox status alterations in the diaphragm

Abstract

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 h of MV. Compared with controls, diaphragms from MV animals demonstrated increased oxidant production, diminished total antioxidant capacity, 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 diaphragm following MV (2.4- and 1.6-fold, respectively), although no change was detected in the levels of either protein. Furthermore, copper-zinc superoxide dismutase and glutathione peroxidase mRNA were not altered following MV, although protein content decreased −1.3- and −1.7-fold, respectively. We conclude that MV promotes increased oxidant production and impairment of key antioxidant defenses in the diaphragm; collectively, these changes contribute to the MV-induced oxidative stress in this key inspiratory muscle.