title: Sodium nitrite mitigates ventilator-induced lung injury in rats.
abstract: BACKGROUND
  Nitrite (NO2) is a physiologic source of nitric oxide and protects against ischemia-reperfusion injuries. We hypothesized that nitrite would be protective in a rat model of ventilator-induced lung injury and sought to determine if nitrite protection is mediated by enzymic catalytic reduction to nitric oxide.
  
  
  METHODS
  Rats were anesthetized and mechanically ventilated. Group 1 had low tidal volume ventilation (LVT) (6 ml/kg and 2 cm H2O positive end-expiratory pressure; n=10); group 2 had high tidal volume ventilation (HVT) (2 h of 35 cm H2O inspiratory peak pressure and 0 cm H2O positive end-expiratory pressure; n=14); groups 3-5: HVT with sodium nitrite (NaNO2) pretreatment (0.25, 2.5, 25 μmol/kg IV; n=6-8); group 6: HVT+NaNO2+nitric oxide scavenger 2-(4-carboxyphenyl)-4,5dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3oxide(n=6); group 7: HVT+NaNO2+nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (n=7); and group 8: HVT+NaNO2+xanthine oxidoreductase inhibitor allopurinol (n=6). Injury assessment included physiologic measurements (gas exchange, lung compliance, lung edema formation, vascular perfusion pressures) with histologic and biochemical correlates of lung injury and protection.
  
  
  RESULTS
  Injurious ventilation caused statistically significant injury in untreated animals. NaNO2 pretreatment mitigated the gas exchange deterioration, lung edema formation, and histologic injury with maximal protection at 2.5 μmol/kg. Decreasing nitric oxide bioavailability by nitric oxide scavenging, nitric oxide synthase inhibition, or xanthine oxidoreductase inhibition abolished the protection by NaNO2.
  
  
  CONCLUSIONS
  Nitrite confers protection against ventilator-induced lung injury in rats. Catalytic reduction to nitric oxide and mitigation of ventilator-induced lung injury is dependent on both xanthine oxidoreductase and nitric oxide synthases.
authors: Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum, Charité-Universitätsmedizin, Berlin, Germany. philipp.pickerodt@charite.de
authors: Philipp A
authors: PA
authors: Pickerodt
authors: Michael J
authors: MJ
authors: Emery
authors: Rachel
authors: R
authors: Zarndt
authors: William
authors: W
authors: Martin
authors: Roland C E
authors: RC
authors: Francis
authors: Willehad
authors: W
authors: Boemke
authors: Erik R
authors: ER
authors: Swenson
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D010100:Oxygen / Q000097:blood; D011175:Positive-Pressure Respiration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000627:therapeutic use*; D055397:Ventilator-Induced Lung Injury / Q000188:drug therapy*; D014968:Xanthine Dehydrogenase / Q000502:physiology
chemical_list: D016207:Cytokines; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D014968:Xanthine Dehydrogenase; D012977:Sodium Nitrite; D010100:Oxygen