Sodium Nitrite Mitigates Ventilator-induced Lung Injury in Rats
Sodium Nitrite Mitigates Ventilator-induced Lung Injury in Rats
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DOI：
10.1097/aln.0b013e3182655f80
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发表时间：
2012-09-01
期刊：
影响因子：
8.8
通讯作者：
Swenson, Erik R.
中科院分区：
文献类型：
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作者：
Pickerodt, Philipp A.;Emery, Michael J.;Swenson, Erik R.
背景：亚硝酸盐（NO2-）是一氧化氮的生理来源，对缺血再灌注损伤具有保护作用。我们假设，亚硝酸盐将在大鼠呼吸机诱导的肺损伤模型的保护，并试图确定亚硝酸盐的保护介导的酶催化还原为nitricoxide.Methods：大鼠麻醉和机械通气。组1采用低潮气量通气（LVT）（6 ml/kg和2 cm H2O呼气末正压; n = 10）;组2采用大潮气量通气（HVT）（3 - 5 cm H2O吸气峰压和0 cm H2O呼气末正压2小时; n = 14）;组3-5：HVT与亚硝酸钠（NaNO 2）预处理（0.25、2.5、25 μ mol/kg IV; n = 6-8）;组6：HVT + NaNO 2+一氧化氮清除剂2-（4-羧基苯基）-4，5-二氢-4，4，5，5-四甲基-1H-咪唑基-1-氧-3-氧化物（n = 6）;第7组：HVT + NaNO 2+一氧化氮合酶抑制剂N-ω-硝基-L-精氨酸甲酯（n = 7）;和第8组：HVT + NaNO 2+黄嘌呤氧化还原酶抑制剂别嘌呤醇（n = 6）。损伤评估包括生理测量（气体交换，肺顺应性，肺水肿的形成，血管灌注压）与肺损伤和protection.Results的组织学和生化相关性：损伤性通气造成统计学显着的伤害在未经处理的动物。NaNO 2预处理减轻了气体交换恶化，肺水肿形成和组织学损伤，2.5 μ mol/kg时保护作用最大。通过清除一氧化氮、抑制一氧化氮合酶或抑制黄嘌呤氧化还原酶来降低一氧化氮的生物利用度，可消除亚硝酸钠的保护作用。结论：亚硝酸盐对大鼠呼吸机相关肺损伤具有保护作用。黄嘌呤氧化还原酶和一氧化氮合酶催化还原为一氧化氮并减轻呼吸机诱导的肺损伤。
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) (2h 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 mu mol/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-omega-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 mu mol/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.