Sodium nitrite mitigates ventilator-induced lung injury in rats
Pickerodt PA, Emery MJ, Zarndt R, Martin W, Francis RCE, Boemke W, Swenson ER (2012)
Publication Type: Journal article
Publication year: 2012
Journal
Book Volume: 117
Pages Range: 592-601
Journal Issue: 3
DOI: 10.1097/ALN.0b013e3182655f80
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. Copyright © 2012, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.
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APA:
Pickerodt, P.A., Emery, M.J., Zarndt, R., Martin, W., Francis, R.C.E., Boemke, W., & Swenson, E.R. (2012). Sodium nitrite mitigates ventilator-induced lung injury in rats. Anesthesiology, 117(3), 592-601. https://doi.org/10.1097/ALN.0b013e3182655f80
MLA:
Pickerodt, Philipp A., et al. "Sodium nitrite mitigates ventilator-induced lung injury in rats." Anesthesiology 117.3 (2012): 592-601.
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