犬烟雾吸入性损伤吸入一氧化氮肺脏病理改变与肺能量代谢的变化

目的：评价犬烟雾吸入性损伤吸入一氧化氮（ＮＯ）肺脏病理改变与肺组织能量代谢的变化。方法：２１只犬随机分为３组，烟雾吸入损伤后，对照组（ｎ＝８）单纯吸氧（ＦｉＯ２，０．４５），治疗组（ｎ＝９）吸氧（ＦｉＯ２，０．０４５）＋０．００４５％（４５ｐｐｍ）ＮＯ，正常组（ｎ＝４）不致伤，用于建立病理和组织学对照。实验终点进行肺组织学和病理形态学检测。结果：对照组ＡＴＰ含量和能量负荷（ＥＣ）显著低于正常和治疗组（Ｐ＜０．０１），ＡＤＰ和ＡＭＰ含量明显低于正常组（Ｐ＜０．０５），而与治疗组相比无显著差别（Ｐ＞０．０５）；肺脏光镜和电镜病理所见，治疗组病理性改变程度较对照组轻。结论：在烟雾吸入性损伤犬模型中，吸入ＮＯ可不同程度改善肺组织能量代谢，肺脏病理形态改变也有一定程度减轻，表明治疗方法有一定效果     

吸入一氧化氮对犬烟雾吸入性损伤血液流变学的影响

目的评价犬烟雾吸入性损伤吸入一氧化氮（ＮＯ）对血液流变学的影响。方法１７只犬随机分二组，烟雾吸入后，对照组（ｎ＝８）单纯吸氧（ＦｉＯ２，０４５），治疗组（ｎ＝９）吸氧（ＦｉＯ２，０４５）＋０００４５％ＮＯ，连续监测血液流变学有关参数，数据行多个样本均数间方差分析和相关分析。结果治疗组ＲＢＣ数和ＲＢＣ压积（Ｈｃｔ）比对照组显著降低（Ｐ＜００５）；ＲＢＣ聚集指数（ＥＡＩ）比对照组降低而ＲＢＣ刚性指数（ＥＲＩ）则升高（Ｐ＜００５～００１）；低切全血粘度（Ｌηｂ）、全血还原粘度（Ｌηｈ）和血浆粘度（ηＰ），治疗组比对照组明显降低（Ｐ＜００５～００１）；治疗组ＮＯ含量升高与ＥＡＩ、Ｌηｈ和ηＰ降低呈显著负相关（ｒ值分别为－０９４，－０９５，－０９３，Ｐ均＜００１）。结论吸入性损伤后血液粘度也有不同程度升高，吸入ＮＯ有不同程度降低吸入性损伤血液的高凝趋势，值得进一步研究     

一氧化氮吸入疗法对烟雾吸入性损伤犬心脏能量代谢和病理变化的研究

目的：评价烟雾吸入性损伤犬吸入一氧化氮（ＮＯ）后心脏病理改变与心室肌组织能量代谢的变化。方法：２１只犬随机分为３组,烟雾吸入损伤后,对照组（８只）单纯吸氧（ＦｉＯ２＝０．４５）,治疗组（９只）吸氧（ＦｉＯ２＝０．４５）＋０．００４５％ＮＯ,正常组（４只）不致伤,用于病理和组织学对照。实验终点进行心室肌组织学和病理形态学检测。结果：对照组ＡＴＰ含量和能量负荷（ＥＣ）显著低于正常组和治疗组（Ｐ均＜０．０１）,对照组ＡＤＰ和ＡＭＰ含量明显低于正常组（Ｐ均＜０．０１）,但ＡＤＰ明显高于治疗组（Ｐ＜０．０５）;心脏光镜和电镜病理所见,治疗组病理性改变程度较对照组轻。结论：在烟雾吸入性损伤犬模型中,吸入ＮＯ可不同程度改善心肌组织能量代谢,心脏病理形态改变也有一定程度减轻,表明ＮＯ吸入疗法对改善心脏能量代谢和病理改变有益。     

吸入一氧化氮对烟雾吸入性损伤犬肺组织含水量的影响

目的：观察吸入一氧化氮（ＮＯ）对烟雾吸入性损伤犬肺组织含水量的影响。方法：２１只犬随机分为３组：烟雾吸入后单纯吸氧〔氧浓度（ＦｉＯ２）０．４５〕为对照组（８只）；吸氧（ＦｉＯ２０．４５）＋０．００４５％ＮＯ为治疗组（９只），按时相点采血标本；正常组（４只）不致伤，用于建立组织学对照。动脉血浆胶体渗透压（ＣＯＰ）行多个样本均数间方差分析；支气管肺泡灌洗液（ＢＡＬＦ）中ＣＯＰ和蛋白质含量行两样本均数ｔ检验。结果：吸入ＮＯ治疗组血浆ＣＯＰ比对照组升高（Ｐ＜０．０５）；ＢＡＬＦ中ＣＯＰ比对照组略降低（Ｐ＞０．０５），而ＢＡＬＦ中蛋白质含量比对照组明显降低（Ｐ＜０．０５）；肺组织含水量略低于对照组（Ｐ＞０．０５）。结论：吸入ＮＯ对烟雾吸入性损伤犬肺组织含水量有减轻趋势，但尚无显著的效果，对其病理转归的影响仍难以定论，有待进一步深入研究。     

一氧化氮对吸入性损伤犬肺功能的改善作用及机制

目的：评价吸入一氧化氮（ＮＯ）对烟雾吸入性损伤犬肺功能的改善效果，并验证其作用机制。方法：２１只犬随机分为３组，烟雾吸入后的对照组（８只）给予单纯吸氧（ＦｉＯ２０．４５）；治疗组（９只）吸氧（ＦｉＯ２０．４５）＋０．００４５％ＮＯ，连续监测１２小时血气变化；正常组（４只）不致伤，用于建立组织学对照。数据行多个样本均数间方差分析。结果：治疗组肺氧合功能明显改善（Ｐ均＜０．０５），肺通气功能也明显改善（Ｐ均＜０．０５）；动脉血和肺组织环磷酸鸟苷（ｃＧＭＰ）明显升高（Ｐ均＜０．０１）。结论：吸入ＮＯ能明显改善肺功能，其作用机制为提高平滑肌细胞内ｃＧＭＰ水平。推荐临床应用吸入ＮＯ作为吸入性损伤的综合治疗方法。     

一氧化氮吸入疗法对烟雾吸入性损伤犬心脏能量代谢和病 …

目的：评价烟雾吸入性损伤犬吸入一氧化氮后心脏病理与心室肌组织能量代谢的变化。方法：２１只犬随机分为３组,烟雾吸入损伤后,对照组单纯吸氧,治疗组吸氧（ＦｉＯ２＝０．４５）＋０００４５％ＮＯ,正常组不致伤,用于病理和组织学对照。实验终点进行心室肌组织学和病理形态学检测。     

一种简单的吸入一氧化氮的输送系统

目的　　解决国内在缺乏昂贵ＮＯ浓度监测仪的情况下应用一氧化氮吸入疗法技术的难题。方法　　１７只犬随机分为二组，吸入性损伤模型成功后，对照组单纯吸氧（ＦｉＯ２，０．４５），治疗组吸氧（ＦｉＯ２，０．４５）＋０．００４５％（４５ｐｐｍ）ＮＯ。ＮＯ输送系统由三个转子流量计分别控制 Ｏ２，Ｎ２和 ＮＯ三种气体管道出口，按需调节三股气体流量比例，在呼吸回路的吸入支置钠石灰罐。 ＦｉＯ２和二氧化氮（（ＮＯ２）数据行多个样本均间方差分析，ＮＯ行两样本均数间ｔ检验。结果ＦｉＯ２实测值比预计值高１０．８％（Ｐ＞０．０５），ＮＯ２在钻石灰处理后比钠石灰处理前降低８０．２％（Ｐ＜０．０１），ＮＯ实测值比预计值高１１％（Ｐ＞０．０５）。结论　　本系统既避免了产生过高ＮＯ２的危险，同时又克服了ＮＯ浓度不恒定的缺点，能较好地满足基础实验研究。     

高频双向喷射通气和常规机械通气对蒸气吸入性损伤犬治疗效果的比较

目的：观察高频双向喷射通气（ＨＦＴＪＶ）和常规机械通气（ＣＭＶ）对蒸气吸入性损伤犬的呼吸循环动力学参数、肺容量及血气的影响。方法：通过蒸气吸入致伤，复制了犬重度蒸气吸入性损伤模型。结果：①两种通气方式下呼吸系统总阻力（Ｒｒｓ）、肺阻力（ＲＬ）均显著高于对照值（Ｐ均＜０．０１），呼吸系统总顺应性（Ｃｒｓ）、肺顺应性（ＣＬ）均显著低于对照值（Ｐ均＜０．０５），但两者之间比较，Ｒｒｓ、ＲＬ和Ｃｒｓ、ＣＬ的变化均无显著性差异（Ｐ均＞０．０５）。②ＣＭＶ能引起ＣＯ２潴留；ＨＦＴＪＶ比ＣＭＶ显著增加ＣＯ２排出量（ＶＣＯ２，Ｐ＜０．０５），降低过高的ＰａＣＯ２（Ｐ＜０．０１）。③两种通气方式下功能残气量（ＦＲＣ）、心输出量（ＣＯ）、平均动脉压（ＭＡＰ）和ＰａＯ２均无显著变化（Ｐ均＞０．０５）。结论：两种通气方式均能克服气道阻力辅助呼吸，但不能使伤后高气道阻力和低肺顺应性恢复正常。ＣＭＶ的通气效率较低，可引起ＣＯ２潴留；ＨＦＴＪＶ的通气效率则明显优于ＣＭＶ，且能维持吸入性损伤犬的血气至正常水平。     

吸入一氧化氮治疗兔油酸急性呼吸窘迫综合征

目的：探讨吸入一氧化氮（ＮＯ）对急性呼吸窘迫综合征（ＡＲＤＳ）肺换气功能的影响及其毒副作用。方法：油酸诱发新西兰兔ＡＲＤＳ模型后分组（ｎ＝９）进行机械通气治疗４ｈｒ：（１）对照组；（２）吸入２０ｐｐｍＮＯ（ＮＯ组）。于动物实验的基础状态、治疗前测定ＰａＯ２／ＦｉＯ２、肺内静动脉分流（Ｑ·ｓ／Ｑ·ｔ）、血ＮＯ２－／ＮＯ３－和高铁血红蛋白（ＭｅｔＨｂ），治疗后ＰａＯ２／ＦｉＯ２于１、２、４ｈｒ，其余指标于４ｈｒ复查一次。观察肺病理并测定肺湿干重比（Ｗ／Ｄ）。结果：治疗后，对照组ＰａＯ２／ＦｉＯ２较治疗前呈下降趋势（４ｈｒ，Ｐ＜０．０５），Ｑ·ｓ／Ｑ·ｔ增加（４ｈｒ，Ｐ＜０．０１），ＮＯ组各时点ＰａＯ２／ＦｉＯ２均较治疗前和同时点的对照组明显增加（Ｐ＜０．０１～０．０５），Ｑ·ｓ／Ｑ·ｔ明显低于治疗前和同时点的对照组（４ｈｒ，Ｐ＜０．０５，Ｐ＜０．０１）。实验结束时，ＮＯ组ＮＯ２－／ＮＯ３－和ＭｅｔＨｂ较对照组显著增加（Ｐ＜０．０５，Ｐ＜０．０１），两组的肺病理和Ｗ／Ｄ无明显区别。结论：吸入２０ｐｐｍ能够明显改善兔油酸型ＡＲＤＳ的肺换气功能，无明显近期毒副作用     

一种新高频通气方法对实验性急性呼吸窘迫综合征的疗效观察

在高频喷射通气（ＨＦＪＶ）治疗犬实验性急性呼吸窘迫综合征（ＡＲＤＳ）时，采用连续ＨＦＪＶ基础上间歇叠加深吸气（ＨＦＪＶ＋ＤＩ）的新通气方法，以期为ＡＲＤＳ的治疗寻找一种新途径。用油酸复制犬ＡＲＤＳ模型，并随机分为３组。ＨＦＪＶ＋ＤＩ组（ｎ＝１０）：在连续ＨＦＪＶ基础上每隔１０分钟加入１次深吸气；常规机械通气组（ＣＭＶ，ｎ＝１０），给予０．７８５ｋＰａ（１ｋＰａ＝１０．２０ｃｍＨ２Ｏ）呼气末正压（ＰＥＥＰ）治疗；对照组（ｎ＝１０），未予通气治疗。每隔１小时测定１次氧合及血流动力学指标，共观察５小时。注射油酸后，动脉氧分压（ＰａＯ２）由１２．４００ｋＰａ（１ｋＰａ＝７．５ｍｍＨｇ）降至６．５６０ｋＰａ（Ｐ＜０．０１），动脉二氧化碳分压（Ｐａ－ＣＯ２）未见明显变化。通气治疗后，ＣＭＶ和ＨＦＪＶ＋ＤＩ均使ＰａＯ２明显升高，ＰａＣＯ２无明显变化（Ｐ＞０．０５），ＨＦＪＶ＋ＤＩ的氧释放指数（ＤＯ２Ｉ）明显高于ＣＭＶ组（Ｐ＞０．０５），心脏指数（ＣＩ）在ＣＭＶ组及ＨＦＪＶ＋ＤＩ组均明显减低（Ｐ＜０．０５）。提示：ＨＦＪＶ＋ＤＩ时ＰａＯ２的提高大于ＣＩ下降所致的不利影响，在改善组织缺氧方面明显优于ＣＭＶ时加用ＰＥＥＰ     

Beneficial effects of concomitant neuronal and inducible nitric oxide synthase inhibition in ovine burn and inhalation injury

Different isoforms of nitric oxide (NO) synthase are critically involved in the development of pulmonary failure secondary to acute lung injury. Here we tested the hypothesis that simultaneous blockade of inducible and neuronal NO synthase effectively prevents the pulmonary lesions in an ovine model of acute respiratory distress syndrome induced by combined burn and smoke inhalation injury. Chronically instrumented sheep were allocated to a sham-injured group (n = 6), an injured and untreated group (n = 6), or an injured group treated with simultaneous infusion of selective inducible and neuronal NO synthase inhibitors (n = 5). The injury was induced by 48 breaths of cotton smoke and a third-degree burn of 40% total body surface area. All sheep were mechanically ventilated and fluid resuscitated. The injury induced severe pulmonary dysfunction as indicated by decreases in PaO2/FiO2 ratio and increases in pulmonary shunt fraction, ventilatory pressures, lung lymph flow, and lung wet/dry weight ratio. The treatment fully prevented the elevations in lymph and plasma nitrate/nitrite levels, pulmonary shunting, ventilatory pressures, lung lymph flow, and wet/dry weight ratio and significantly attenuated the decline in PaO2/FiO2 ratio. In conclusion, simultaneous blockade of inducible and neuronal NO synthase exerts beneficial pulmonary effects in an ovine model of acute respiratory distress syndrome secondary to combined burn and smoke inhalation injury. This novel treatment strategy may represent a useful therapeutic adjunct for patients with these injuries.     

7-硝基吲唑在烟雾吸入性肺损伤中的作用

目的 探讨神经型一氧化氮合酶（nNOS）抑制剂7-硝基吲唑（7-NI）在烟雾吸入性肺损伤中的作用。方法 40只SD雄性大鼠被随机分为正常对照组（n=8）、烟雾吸入性肺损伤模型组（n=16）和7-NI治疗组（n=16），建立烟雾吸入性肺损伤模型。7-NI治疗组在致伤后立即腹腔注射7-NI 20mg／kg（溶于2ml花生油中）；正常对照组及模型组腹腔注射2ml花生油。分别于伤后2、6、12和24h时间点监测动脉血气分析；并分批处死大鼠，取肺组织测肺含水量，制备肺组织匀浆检测超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、各型一氧化氮合酶（NOS）活性及肿瘤坏死因子-α（TNF—α）和一氧化氮（NO）含量。光镜下观察肺组织病理学变化。结果 与模型组比较，7～NI治疗组各时间点动脉血氧分压均显著升高（P均〈0．05），肺组织含水量显著降低（P〈0．05），肺组织中SOD及CAT活性均明显升高（P均〈0．05），nNOS活性及NO含量均明显降低（P均〈0．05）。治疗组2h和6h肺组织中TNF—α含量均较模型组降低（P均〈0．05）。光镜下7-NI治疗组较模型组损伤程度减轻，炎性细胞浸润减少，肺间质内未见点状出血。结论 7-NI对烟雾吸人性肺损伤有较好的保护作用，可提高动脉血氧分压，减轻肺水肿程度，增加组织抗氧化能力，并减轻组织炎性细胞浸润。     

Aerosol delivery of diethylenetriamine/nitric oxide, a nitric oxide adduct, causes selective pulmonary vasodilation in perinatal lambs.

Postnatal adaptation of the pulmonary circulation is mediated partly by endothelium-derived nitric oxide (NO). Recent studies have demonstrated that inhaled NO causes selective and sustained vasodilation in infants with persistent pulmonary hypertension of the newborn. Because the short half-life of NO limits its clinical application, we hypothesized that aerosol delivery of an NO-adduct, diethylenetriamine (DETANO), can cause sustained and selective pulmonary vasodilation. To test the acute effects of DETANO, we studied the pulmonary vascular response of late-gestation fetal lambs (n = 8; age = 138 days; term = 147) to aerosolized DETANO in the presence of an endothelium-derived NO inhibitor, nitro-L-arginine. To determine whether DETANO has a sustained effect, fetal lambs were ventilated with FiO2 0.10 before and 15 minutes after they were treated with aerosolized DETANO. Fetal lambs were acutely prepared. Nitro-L-arginine (1 mg/min x 30 minutes) was infused into the left pulmonary artery before ventilation with FiO2 1.00 for 30 minutes, followed by continued ventilation with FiO2 0.10 for 10 minutes. This represented the control period. Ventilation was continued with FiO2 1.00, and aerosolized DETANO was given in doses of 0.1, 0.4, and 1.0 mg. Fifteen minutes after the last dose of DETANO was administered, animals were ventilated with FiO2 0.10. In the control period, during ventilation with FiO2 0.10, left pulmonary artery flow was 122+/-33 mL/min and decreased to 104+/-22 mL/min. Aerosol delivery of DETANO increased left pulmonary artery flow to 176+/-26 mL/min (P<.05) and had no effect on aortic pressure or heart rate. After DETANO was administered, ventilation with FiO2 0.10 did not cause any change in left pulmonary artery flow. We conclude that DETANO can cause selective fetal pulmonary vasodilation. Aerosol delivery of DETANO may increase the clinical applications of NO.     

The effect of inducible nitric oxide synthase (iNOS) inhibition on smoke inhalation injury in sheep

Recent studies on smoke inhalation injury have been focused on nitric oxide (NO) as an essential factor of progressive lung injury. We studied the effects of inducible nitric oxide synthase (iNOS) inhibition on inhalation injury in sheep. Sheep (n = 14) were prepared surgically for chronic study. After recovery period, the sheep received 48 breaths of cotton smoke. The animals were then randomised into two groups: MEG group [30 mg/kg mercaptoethylguanidine (MEG), selective inhibitor of iNOS and peroxynitrite scavenger, was given 1 h after injury and then 8 h for 41 h, n = 7] and control group (0.9% NaCl, n = 7). All animals were ventilated mechanically, and airway blood flow was measured using colored microspheres. In the control group, following significant increase in airway blood flow, deterioration in the PaO2/FiO2 ratio was observed. Whereas in the MEG group, it was not observed. In addition, the MEG group did not show significant increase in pulmonary vascular resistance and intrapulmonary shunt fraction. Lung wet/dry ratios, a marker of pulmonary edema, were significantly lower in the MEG group. At 48 h after injury, lung tissue-conjugated dienes, an index of lung oxidative tissue injury, were significantly lower in the MEG group than in the control group. Our data suggest that 1) iNOS-NO produced in the airway circulation plays a major role on the significant increase in airway blood flow, which may contribute to the spread of injury from injured airway to the lung parenchyma; 2) iNOS-NO induced in the pulmonary circulation contributes to the loss of hypoxic pulmonary vasoconstriction; and 3) iNOS-NO plays an important role on the lung oxidative tissue injury.     

L-arginine attenuates acute lung injury after smoke inhalation and burn injury in sheep

Thermal injury results in reduced plasma levels of arginine (Arg). With reduced Arg availability, NOS produces superoxide instead of NO. We hypothesized that Arg supplementation after burn and smoke inhalation (B + S) injury would attenuate the acute insult to the lungs and, thus, protect pulmonary function. Seventeen Suffolk ewes (n = 17) were randomly divided into three groups: (1) sham injury group (n = 6), (2) B + S injury plus saline treatment (n = 6), and (3) B + S injury plus L-ARG infusion at 57 mg.kg(-1).h(-1) (n = 5). Burn and smoke inhalation injury was induced by standardized procedures, including a 40% area full thickness flame burn combined with 48 breaths of smoke from burning cottons. All animals were immediately resuscitated by Ringer solution and supported by mechanical ventilation for 48 h, during which various variables of pulmonary function were monitored. The results demonstrated that Arg treatment attenuated the decline of plasma Arg concentration after B + S injury. A higher plasma Arg concentration was associated with a less decline in Pao2/Fio2 ratio and a reduced extent of airway obstruction after B + S injury. Histopathological examinations also indicated a remarkably reduced histopathological scores associated with B + S injury. Nitrotyrosine stain in lung tissue was positive after B + S injury, but was significantly reduced in the group with Arg. Therefore, L-Arg supplementation improved gas exchange and pulmonary function in ovine after B + S injury via its, at least in part, effect on reduction of oxidative stress through the peroxynitrite pathway.     

吸入一氧化氮对大鼠肝脏毒副作用的影响

目的　评价吸入外源性一氧化氮 (NO)对正常大鼠肝脏的毒副作用。方法　 72只大鼠随机分为三组 :吸氧组 (G1)单纯吸氧 (FiO2 0 .40 ) ;低浓度NO吸入组 (G2 )和高浓度NO吸入组 (G3 )除吸氧外 ,分别吸入 40 ppm和 80 ppm的NO ,分别于 2、8、12、2 4小时取标本检测 ;另取 6只大鼠做正常值和组织学对照。数据行多个样本均数间方差分析。结果　肝组织含水量三组间无明显差异 (P >0 .0 5 ) ,三组呼出气NO2 浓度G3 比G1和G2 和正常值显著升高 (P <0 .0 1) ,G3 GPT2 4小时明显高于G1(P <0 .0 1)、G2 和正常值 (P <0 .0 5 ) ,G2 TBil2 4小时明显低于G1和G3 ,G3 MHB分别高于G1和G2(P <0 .0 5、P >0 .0 5 ) ,G1和G3 均可见到组织形态学改变 ,G2 组改变则较轻。结论　吸入低浓度NO无明显毒副作用 ,而吸入高浓度NO对肝组织可能有一定的损伤     

Heparin nebulization attenuates acute lung injury in sepsis following smoke inhalation in sheep

Pseudomonas pneumonia is a common complication of smoke inhalation injury. Airway casts formed from clotted mucous occur frequently in this condition. A recent report shows that intravenous heparin improves oxygenation and reduces lung damage in a sheep model of smoke inhalation. We hypothesized that nebulized heparin could be an effective means of reducing cast formation. Female sheep (n = 19) were surgically prepared for a study of acute lung injury (ALI). After a tracheotomy, 48 breaths of cotton smoke (<40 degrees C) were inflated into the airway. Afterwards, live Pseudomonas aeruginosa (5 x 10(11) CFU) was instilled into the lung. All sheep were mechanically ventilated with 100% O2 and were divided into four groups: a heparin-nebulized group (n = 5; animals received aerosolized heparin [10,000 I.U.] 1 h after the bacterial instillation and subsequently every 4 h thereafter), an intravenous heparin group (n = 5,300 U/kg/23 h, infusion was started 1 h after the injury), a saline-nebulization group (n = 5; animals received inhaled nebulized saline), and a sham injury group (n = 4, treated in the same fashion, but no injury). The animals were sacrificed after 24 h of mechanical ventilation, and lung samples were harvested. Sheep exposed to lung injury presented with typical hyperdynamic cardiovascular changes and a corresponding drop in PaO2. These changes were significantly attenuated in the heparin groups. Histological changes consisting of cellular infiltrates, lung edema, congestion, and cast formation were reduced by heparin. These data suggest that nebulized inhaled heparin is a beneficial therapy for sepsis-induced ALI.     

Direct delivery of low-dose 7-nitroindazole into the bronchial artery attenuates pulmonary pathophysiology after smoke inhalation and burn injury in an ovine model

Bronchial circulation plays a critical role in the pathophysiology of burn and smoke inhalation-induced acute lung injury. A 10-fold increase in bronchial blood flow is associated with excessive production of nitric oxide (NO) following smoke inhalation and cutaneous burn. Because an increased release of neuropeptides from the airway has been implicated in smoke inhalation injury, we hypothesized that direct delivery into the bronchial artery of low-dose 7-nitroindazole (7-NI), a specific neuronal NO synthase inhibitor, would attenuate smoke/burn-induced acute lung injury. Eighteen adult female sheep were instrumented for chronic hemodynamic monitoring 5 to 7 days before the injury. The bronchial artery was cannulated via intercostal thoracotomy, while blood flow was preserved. Acute lung injury was induced by 40% total body surface area third-degree cutaneous burn and smoke inhalation (48 breaths of cotton smoke, <40°C) under deep anesthesia. Following injury, animals (35.4 ± 1.1 kg) were divided into three groups: (a) 7-NI group: 1 h after injury, 7-NI (0.01 mg · kg · h, 2 mL · h) was continuously infused into the bronchial artery, n = 6; (b) control group: 1 h after injury, same amount of saline was injected into the bronchial artery, n = 6; (c) sham group: no injury, no treatment, same operation and anesthesia, n = 6. After injury, all animals were ventilated and fluid resuscitated according to an established protocol. The experiment was conducted for 24 h. Injury induced severe pulmonary dysfunction, which was associated with increases in lung edema formation, airway obstruction, malondialdehyde, and nitrate/nitrite. 7-Nitroindazole injection into the bronchial artery reduced the degree of lung edema formation and improved pulmonary gas exchange. The increase in malondialdehyde and nitrate/nitrite in lung tissue was attenuated by treatment. Our data strongly suggest that local airway production of NO contributes to pulmonary dysfunction following smoke inhalation and burn injury. Most mechanisms that drive this pathophysiology reside in the airway.