Apocynin attenuates mechanical ventilation‐induced diaphragmatic oxidative stress and contractile dysfunction

• Published in: The FASEB journal 2006-03, Vol.20 (5), p.A1160-A1160
• Main Authors: Van Gammeren, Darin L, Falk, Darin J, Deering, Melissa A, DeRuisseau, Keith C, French, Joel P, Powers, Scott K
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.5.A1160-c

Mechanical ventilation is associated with diaphragmatic oxidative stress and contractile dysfunction. However, the pathways responsible for the production of oxidants in the diaphragm during mechanical ventilation remain unknown. We tested the hypothesis that apocynin, a known NADPH oxidase inhibitor, would attenuate the diaphragmatic oxidative stress and contractile dysfunction that occurs during mechanical ventilation. Female, Sprague‐Dawley rats were mechanically ventilated for 18 hours while receiving saline or apocynin (4 mg/kg body weight, IP). Diaphragms from time‐matched spontaneously breathing and acutely anesthetized animals served as controls. Compared to control, mechanically ventilated diaphragms exhibited a decrease in maximal specific force (−10%). Furthermore, mechanical ventilation was associated with diaphragmatic oxidative stress as evident by lowered diaphragmatic reduced glutathione levels (−50%) and elevated protein carbonyls (24%). However, the administration of apocynin abolished the mechanical ventilation‐induced contractile dysfunction and protein carbonyl formation in the diaphragm while attenuating reductions in diaphragmatic glutathione levels. Therefore, these results indicate that apocynin can attenuate mechanical ventilation‐induced diaphragm contractile dysfunction and oxidative stress. This work supported by NIH RO1 HL072789 awarded to S.K.P.