title: Mechanical ventilation-induced oxidative stress in the diaphragm: role of heme oxygenase-1.
abstract: BACKGROUND
  Prolonged mechanical ventilation (MV) results in a rapid onset of diaphragmatic atrophy that is primarily due to increased proteolysis. Although MV-induced protease activation can involve several factors, it is clear that oxidative stress is a required signal for protease activation in the diaphragm during prolonged MV. However, the oxidant-producing pathways in the diaphragm that contribute to MV-induced oxidative stress remain unknown. We have demonstrated that prolonged MV results in increased diaphragmatic expression of a key stress-sensitive enzyme, heme oxygenase (HO)-1. Paradoxically, HO-1 can function as either a pro-oxidant or an antioxidant, and the role that HO-1 plays in MV-induced diaphragmatic oxidative stress is unknown. We tested the hypothesis that HO-1 acts as a pro-oxidant in the diaphragm during prolonged MV.
  
  
  METHODS
  To determine whether HO-1 functions as a pro-oxidant or an antioxidant in the diaphragm during MV, we assigned rats into three experimental groups: (1) a control group, (2) a group that received 18 h of MV and saline solution, and (3) a group that received 18 h of MV and was treated with a selective HO-1 inhibitor. Indices of oxidative stress, protease activation, and fiber atrophy were measured in the diaphragm.
  
  
  RESULTS
  Inhibition of HO-1 activity did not prevent or exacerbate MV-induced diaphragmatic oxidative stress (as indicated by biomarkers of oxidative damage). Further, inhibition of HO-1 activity did not influence MV-induced protease activation or myofiber atrophy in the diaphragm.
  
  
  CONCLUSIONS
  Our results indicate that HO-1 is neither a pro-oxidant nor an antioxidant in the diaphragm during MV. Furthermore, our findings reveal that HO-1 does not play an important role in MV-induced protease activation and diaphragmatic atrophy.
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL.
authors.forename: Darin J
authors.initials: DJ
authors.lastname: Falk
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL.
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Kavazis
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Whidden
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Smuder
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McClung
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Hudson
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL. Electronic address: spowers@hhp.ufl.edu.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Powers
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003964:Diaphragm / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D051547:Heme Oxygenase-1