Related Experiment Video
Updated: May 20, 2026
A Rat Lung Transplantation Model of Warm Ischemia/Reperfusion Injury: Optimizations to Improve Outcomes
Published on: October 28, 2021
Sodium nitrite mitigates ventilator-induced lung injury in rats
Philipp A Pickerodt1, Michael J Emery, Rachel Zarndt
1Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum, Charité-Universitätsmedizin, Berlin, Germany. philipp.pickerodt@charite.de
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.
