Mitochondria-targeted antioxidants protect against mechanical ventilation-induced XXXX .

@entity1 @entity26 @entity409 @entity425 @entity194 @entity1576 @entity35 @entity2383
BACKGROUND: Mechanical ventilation is a life-saving intervention used to provide adequate pulmonary ventilation in @entity1 suffering from @entity1576 . However, prolonged mechanical ventilation is associated with significant @entity425 resulting from both myofiber @entity194 and @entity409 . Although several signaling pathways contribute to @entity425 during mechanical ventilation, it is established that oxidative stress is required for @entity425 to occur. Therefore, identifying the site(s) of mechanical ventilation- induced reactive @entity26 species production in the diaphragm is important. OBJECTIVE: These experiments tested the hypothesis that elevated mitochondrial reactive @entity26 species emission is required for mechanical ventilation-induced oxidative stress, @entity194 , and @entity409 in the diaphragm. DESIGN: Cause and effect was determined by preventing mechanical ventilation-induced mitochondrial reactive @entity26 species emission in the diaphragm of @entity35 using a novel mitochondria-targeted antioxidant (SS-31). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared to mechanically ventilated animals treated with saline, animals treated with SS-31 were protected against mechanical ventilation-induced @entity2383 , oxidative stress, and protease activation in the diaphragm. Importantly, treatment of animals with the mitochondrial antioxidant also protected the diaphragm against mechanical ventilation-induced myofiber @entity194 and @entity409 . CONCLUSIONS: These results reveal that prevention of mechanical ventilation-induced increases in diaphragmatic mitochondrial reactive @entity26 species emission protects the diaphragm from mechanical ventilation-induced @entity425 . This important new finding indicates that mitochondria are a primary source of reactive @entity26 species production in the diaphragm during prolonged mechanical ventilation. These results could lead to the development of a therapeutic intervention to impede mechanical ventilation-induced @entity425 .
