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。     

吸入一氧化氮改善烟雾吸入性损伤犬肺通气功能的意义

目的评价吸入一氧化氮（ＮＯ）对犬烟雾吸入性损伤肺通气功能改善的效果。方法烟雾吸入伤后，将１７只犬随机分为２组，对照组（ｎ＝８）单纯吸氧（ＦｉＯ２，０．４５），治疗组（ｎ＝９）吸氧（ＦｉＯ２，０．４５）＋０．００４５％（４５ｐｐｍ）ＮＯ，连续监测１２小时血气变化；并按时相点抽血检测有关指标。数据行多个样本均数间方差分析。结果吸入ＮＯ治疗组ＰａＣＯ２、呼吸指数（ＲＩ）、肺泡死腔率（ＶＤ／ＶＴ）、肺动脉分流率（ＱＳ／ＱＴ）和碳氧血红蛋白（ＨｂＣＯ）含量比对照组均有不同程度的下降（Ｐ＜０．０５～０．０１），而动脉血浆亚硝酸盐（ＮＯ－２）水平则明显高于对照组（Ｐ＜０．０１）。结论吸入ＮＯ能明显改善肺通气功能，作为吸入性损伤的综合治疗，吸入ＮＯ疗法值得进一步研究。     

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。     

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。     

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     

肺表面活性物质治疗急性呼吸窘迫综合征的实验研究

目的：观察外源性肺表面活性物质（ＰＳ）对实验性急性呼吸窘迫综合征（ＡＲＤＳ）的疗效。方法：１８只新西兰白兔油酸诱发ＡＲＤＳ后，９只在机械通气基础上经气道滴入猪ＰＳ（１００ｍｇ／ｋｇ，为ＰＳ组），另外９只给于单纯机械通气作为对照组，均观察４小时。于动物实验的基础状态、治疗前及治疗后１小时、２小时、４小时测定肺功能残气量（ＦＲＣ）、动脉血气和肺泡动脉血氧分压差〔Ｐ（Ａ－ａ）Ｏ２〕。实验结束时观察肺病理形态并测定肺泡容积密度（ＶＶ）。结果：治疗后，对照组ＦＲＣ和动脉血氧分压（ＰａＯ２）／氧浓度（ＦｉＯ２）比值（ＯＩ）呈下降趋势，而ＰＳ组ＦＲＣ和ＯＩ明显高于治疗前和同时间点的对照组（Ｐ＜０．０５或Ｐ＜０．０１），Ｐ（Ａ－ａ）Ｏ２明显低于治疗前和同时间点的对照组（Ｐ＜０．０５或Ｐ＜０．０１）。病理形态观察见对照组广泛性肺不张、肺泡和间质水肿、出血和炎性细胞浸润，ＰＳ组上述改变较轻，ＶＶ增加（Ｐ＜０．０１）。结论：外源性肺表面活性物质对兔油酸型ＡＲＤＳ模型有一定的治疗效果     

复方红景天和参芪花粉合剂防治高原急性肺损伤的实验研究

目的：探索藏药复方红景天（ＲＣＯ）和复方参芪花粉合剂（ＡＣＯ）对高原急性肺损伤（ＡＬＩ）早期的防治作用。方法：２４只兔和１２０只小鼠随机分为生理盐水对照组（ＮＣＧ）、盲肠结扎穿孔（ＣＬＰ）致伤组（ＩＧ），ＡＣＯ防治组（ＡＣＯＧ）、ＲＣＯ防治组（ＲＣＯＧ）。致伤前后按时测定体、肺血流动力学，血气和血、组织匀浆中的血栓素Ｂ２（ＴＸＢ２）、６酮前列腺素Ｆ１α（６ｋｅｔｏＰＧＦ１α）各指标参数。结果：各组动脉血氧分压（ＰａＯ２）和平均肺动脉压（ＭＰＡＰ）在致伤前已出现差异，ＲＣＯＧ和ＮＣＧ及ＩＧ比较，Ｐ均＜０．０５。术后４小时、８小时各组ＰａＯ２、ＴＸＢ２、６ｋｅｔｏＰＧＦ１α变化更明显，ＡＣＯＧ、ＲＣＯＧ与ＮＣＧ及ＩＧ比较，Ｐ＜０．０５或Ｐ＜０．０１。术后１２小时，ＡＣＯＧ和ＲＣＯＧ的平均体动脉压（ＭＡＰ）仍保持ＮＣＧ水平，与ＩＧ比较，Ｐ均＜０．０１。结论：藏药ＲＣＯ和ＡＣＯ在防治高原ＡＬＩ中可能起到重要防护作用     

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.     

Effects of manganese superoxide dismutase, when given after inhalation injury has been established

OBJECTIVES: To determine whether treatment with manganese superoxide dismutase (MnSOD), given intravenously after inhalation injury has been established, improves oxygenation and lung fluid balance. DESIGN: Randomized, controlled intervention trial. SETTING: University research laboratory. SUBJECTS: Twenty-four chronically instrumented awake ewes with lung lymph fistulas. INTERVENTIONS: After smoke inhalation with 48 breaths of cotton smoke, the animals were assigned randomly to a control group (n = 6) or a treatment group, receiving 1000 units of MnSOD/kg (n = 6), 3000 units of MnSOD/kg (n = 6), or 9000 units of MnSOD/kg (n = 6) intravenously 1 hr after smoke inhalation. MEASUREMENTS AND MAIN RESULTS: Different from the other three groups, in the group that received 3000 units of MnSOD, cardiac output and Pao2/Fio2 ratio did not significantly decrease throughout the experimental period. Apart from higher oxygen consumption in the group receiving 3000 units of MnSOD 24 hrs after smoke inhalation (263 +/- 44 mL/min vs. 182 +/- 36 mL/min; p < 0.05), no significant differences between treatment groups and control group were observed. CONCLUSIONS: Treatment with MnSOD given after smoke inhalation seems to be less effective then pretreatment with MnSOD, which was reported in previous studies to reduce the degree of inhalation injury.     

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。     

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     

Concurrent administration of amrinone with nitric oxide most improves PaO2/FiO2 in acute respiratory and cardiac failure.

A 55-year-old man developed acute respiratory failure, pulmonary hypertension and left heart failure due to acute myocardial infarction. Nitric oxide (NO) inhalation improved arterial oxygenation, decreased pulmonary arterial pressure and increased cardiac output (CO), but combined use of dobutamine with NO produced increases in pulmonary arterial pressure and pulmonary capillary wedge pressure (PCWP). In this patient, amrinone decreased pulmonary arterial pressure and PCWP, and increased PaO2/FiO2 effectively while increasing CO. Combined use of inhaled NO and intravenous amrinone may have beneficial effects for a patient with acute respiratory and cardiac failure.     

氨基胍对烟雾吸入性肺损伤的影响

目的探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(aminoguanidine,AG)对大鼠烟雾吸入性肺损伤的影响。方法40只SD雄性大鼠随机分为正常对照组(n=8)、烟雾吸入组(n=16)和AG治疗组(n=16)。建立烟雾吸入性肺损伤模型,AG治疗组于致伤后立即腹腔注射AG50mg/kg。正常对照组及烟雾吸入组腹腔注射等容量生理盐水。分别于2、6、12、24h时相点进行动脉血气分析,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)活性及一氧化氮(NO)含量。制作肺组织病理切片,光镜下观察病理变化。结果与烟雾吸入组相比,AG治疗组动脉血氧分压显著升高(P<0.05),肺组织含水量降低(P<0.05),肺组织中SOD活性及CAT活性升高(P<0.05),iNOS活性及NO含量降低(P<0.05)。结论AG能够升高动脉血氧分压,提高烟雾吸入性肺损伤肺组织抗氧化能力,减轻肺组织氧化性损伤,减轻肺水肿,并减轻组织炎性浸润,对烟雾吸入性肺损伤有较好的保护作用。     

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.