大鼠机械通气所致肺损伤时p38丝裂原活化蛋白激酶通路的激活

目的探讨大鼠机械通气所致呼吸机相关性肺损伤(VILI)时p38丝裂原活化蛋白激酶(MAPK)的激活以及致炎因子的表达。方法30只健康SD大鼠随机均分成A、B、C3组,A组:潮气量(VT)8ml/kg,呼吸频率(RR)80次/min;B组:VT20ml/kg,RR80次/min;C组:VT40ml/kg,RR80次/min。各组机械通气时间均为2h。实验结束处死大鼠,收集支气管肺泡灌洗液(BALF)和肺组织标本,光镜下观察肺组织病理学改变。采用蛋白质免疫印迹法(Western blotting)检测各组肺组织中p38、磷酸化p38(p-p38)水平,逆转录-聚合酶链反应(RT-PCR)检测细胞间黏附分子-1(ICAM-1)表达水平,考马斯亮蓝染色法检测肺组织中总蛋白浓度和髓过氧化物酶(MPO)活性,双抗体夹心酶联免疫吸附法检测BALF中肿瘤坏死因子-α(TNF-α)、巨噬细胞炎症蛋白-2(MIP-2)和白细胞计数(WBC)。结果肺组织病理观察显示,A、B、C3组的改变依次加重;与A组相比,B、C两组p-p38和ICAM-1的表达以及总蛋白、WBC、MIP-2、TNF-α及MPO的水平均显著增高(P均<0.01);与B组相比,C组p-p38和ICAM-1的表达以及总蛋白、WBC、MIP-2、TNF-α及MPO的水平均显著增高(P<0.05或P<0.01)。结论大VT机械通气能显著激活p38通路以及致炎因子的表达,这可能是大鼠机械通气所致肺损伤的重要致病机制之一。     

全麻肌松恢复期不同机械通气模式的研究

目的 :观察全麻患者在肌松恢复期用间歇正压通气 (IPPV)、同步间歇指令通气 (SIMV)、双水平压力正压通气 (Bi PAP)对自主呼吸恢复的影响。方法 :30例手术患者随机均分 3组。术中初始通气方式均为 IPPV,给最后一次肌松剂后将后两组的通气模式分别调整为 SIMV和 Bi PAP。不同时间点记录气道峰压 (Ppeak)、每分通气量 (MV)、呼气末二氧化碳分压 (PEt CO2 )和血气 ,观察给最后一次肌松剂至自主呼吸恢复的时间(L R S)。结果 :1给予最后一次肌松剂后和 T1 出现时 Bi PAP组的 Ppeak均明显低于 IPPV和 SIMV组(P均 <0 .0 1) ,TR=0 .75时 IPPV组的 Ppeak均明显低于 SIMV和 Bi PAP组 (P均 <0 .0 1) ;2 T1 恢复时Bi PAP组的 MV高于 IPPV组 (P<0 .0 5 ) ,T4 恢复、TR=0 .2 5、TR=0 .75时 SIMV和 Bi PAP组的 MV均明显高于 IPPV组 (P均 <0 .0 1) ;3TR=0 .2 5、TR=0 .75时 SIMV和 Bi PAP组的 PEt CO2 均低于 IPPV组 (P均 <0 .0 5 ) ;4拔管前 SIMV和 Bi PAP组的动脉二氧化碳分压 (Pa CO2 )均低于 IPPV组 (P均 <0 .0 5 ) ;5 SIMV组和Bi PAP组的 L R S均短于 IPPV组 (P均 <0 .0 5 )。结论 :SIMV和 Bi PAP具有不对抗患者自主呼吸、L R S短、Ppeak变化小、MV高、PEt CO2 低等优点 ,更适于全麻恢复期使用。 Bi PAP还具有 Ppeak     

胸部开放伤后胸腔海水浸泡致犬急性肺损伤的救治研究

目的 探讨肺保护性通气联合己酮可可碱对胸部开放伤后胸腔内海水致急性肺损伤（ALI）的救治疗效。方法 用胸部开放伤后胸腔内灌注海水制备犬ALI模型。将24条犬随机分为未救治组（A组）、普通救治组（B组）、肺保护性通气组（C组）和肺保护性通气＋己酮可可碱组（D组）。分别于致伤前、致伤6h及救治2h和4h监测各组动物的动脉血气分析、血流动力学、血浆渗透浓度和血钠、血氯的变化；收集外周静脉血和支气管肺泡灌洗液（BALF）检测肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和IL-8含量。结果 B组救治2h和4h后动脉血氧分压（PaO2）及氧合指数（PaO2／FiO2）仍低于正常水平，C组和D组恢复正常；B、C和D组血流动力学指标以及高渗、高钠、高氯血症在救治2h和4h后较A组显著改善。C组外周血TNF—α及D组外周血TNF—α、IL～8和BALF中IL-6、IL-8水平在救治后显著低于A组和B组；D组外周血TNF-α及BALF中IL-8水平亦显著低于C组。结论 应用肺保护性机械通气治疗胸腔海水致ALI可以起到良好的呼吸支持作用，己酮可可碱能有效的抑制肺内、外炎症反应。     

心脏外科肺动脉高压患者围手术期一氧化氮的吸入治疗

目的 探讨一氧化氮(NO)吸入治疗对合并肺动脉高压心脏外科围手术期患者的有效性与安全性.方法 应用Servo 300A呼吸机或Aeronox NO释放与监测仪,对合并肺动脉高压且临床常规治疗效果不理想的27例成人和1例房间隔缺损修补术患儿进行围手术期NO吸入治疗,NO开始剂量(5～10)×10-6,然后根据病情可缓慢升高至20×10-6.于治疗前后监测患者的肺动脉压(PAP)、动脉压(AP)、肺血管阻力(PVR)和氧合指数(PaO2/FiO2).NO吸入治疗的有效标准为治疗开始后1 h内AP/PAP改善20%以上,或PaO2/FiO2改善20%以上.NO吸入治疗1.5 h后无效者终止该方法.结果 成人患者NO吸入治疗有效率为77.8%(21/27例),治疗持续时间为12～96 h,平均(32.6±10.3)h.1例房间隔缺损合并中度肺动脉高压患儿在房间隔缺损修补术后,肺动脉高压加重,合并严重的低氧血症[PaO2/FiO2为40 mm Hg(1 mm Hg=0.133 kPa),吸入氧浓度(FiO2)为1.00],经NO吸入等综合治疗后效果明显,4 d后撤离呼吸机.治疗中与治疗后,在患者与工作人员中未发现不良事件.结论 NO吸入治疗对心脏外科合并肺动脉高压围手术期病情加重者治疗有效,值得进一步临床探索.     

高迁移率族蛋白B1 / Toll样受体4信号通路在脓毒症大鼠致急性肺损伤中的作用研究

目的探讨高迁移率族蛋白B1（HMGB1） / Toll样受体4（TLR4）信号通路对脓毒症导致的急性肺损伤大鼠的影响。 方法将60只清洁级雄性Sprague Dawley大鼠分为假手术组、脓毒症组和实验组,每组各20只。假手术组大鼠麻醉后开腹翻动肠道,随即关腹;脓毒症组和实验组行盲肠结扎穿孔（CLP）术后0.5 h于尾静脉分别注射等渗NaCl溶液（4 mL / kg）及抗HMGB1单克隆抗体（2 mg / kg）。各组分别取10只用于观察大鼠CLP建模后7 d存活情况,其余大鼠于造模后24 h处死并留取肺组织标本。计算各组大鼠的肺损伤Smith评分,并比较各组大鼠HMGB1和TLR4阳性蛋白在肺组织中的表达水平。采用酶联免疫吸附测定检测各组大鼠肺泡灌洗液（BALF）中肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、HMGB1和TLR4水平,计算每个巨噬细胞内微球蛋白数以比较各组大鼠肺泡巨噬细胞（AM）的吞噬功能,并采用Western-blotting法测定AM内HMGB1、TLR4蛋白表达水平。 结果假手术组大鼠建模后7 d全部存活,脓毒症组大鼠仅3只存活,实验组大鼠5只存活。各组大鼠间存活情况的比较,差异有统计学意义（ χ² = 10.833,P = 0.004）;且假手术组大鼠的存活情况明显优于脓毒症组与实验组大鼠（P均< 0.017）,而脓毒症组与实验组大鼠间存活情况比较,差异无统计学意义（P = 0.120）。假手术组、脓毒症组及实验组大鼠间肺组织损伤评分[（2.20 ± 0.27）、（8.20 ± 1.27）、（4.25 ± 2.21）分,F = 56.432,P < 0.001],肺组织HMGB1阳性蛋白[（10.4 ± 1.5）、（34.4 ± 5.0）、（26.6 ± 6.9）,F = 35.203,P = 0.003]、TLR4阳性蛋白[（10.6 ± 2.1）、（48.0 ± 5.8）、（38.2 ± 5.3）,F = 103.414,P = 0.002],BALF中TNF-α[（19 ± 4）、（45 ± 4）、（35 ± 4）μg / L,F = 2.749,P < 0.001]、IL-6[（56 ± 19）、（86 ± 15）、（70 ± 19）μg / L,F = 4.648,P = 0.001]、HMGB1[（41 ± 18）、（70 ± 15）、（56 ± 12）μg / L,F = 7.254,P = 0.002]、TLR4[（20.9 ± 1.8）、（51.2 ± 1.6）、（49.8 ± 2.6）μg / L,F = 3.978,P = 0.035],AM的吞噬功能[（21.8 ± 2.7）、（3.1 ± 1.9）、（12.6 ± 2.2）个,F = 32.821,P = 0.001]及AM中HMGB1蛋白[（11 ± 3）、（40 ± 15）、（24 ± 13）,F = 7.253,P < 0.001]、TLR4蛋白[（0.9 ± 0.4）、（1.2 ± 0.6）、（1.1 ± 0.4）,F = 3.984,P = 0.028]的比较,差异均有统计学意义。进一步两两比较发现,脓毒症组与实验组大鼠肺组织损伤评分,肺组织HMGB1阳性蛋白、TLR阳性蛋白表达水平,BALF中TNF-α、IL-6、HMGB1水平及AM中HMGB1蛋白表达水平均明显高于假手术组大鼠,且脓毒症组大鼠更高（P均< 0.05）;脓毒症组及实验组大鼠AM的吞噬功能均显著低于假手术组,且脓毒症组更低（P均< 0.05）;脓毒症组及实验组大鼠BALF中TLR4水平及AM中TLR4蛋白表达水平均显著高于假手术组（P均< 0.05）,但脓毒症组与实验组间上述指标的比较,差异均无统计学意义（P均> 0.05）。 结论通过抑制HMGB1 / TLR4信号通路可以缓解脓毒症致肺损伤大鼠肺组织的炎症损伤,抑制炎症介质过度释放,并增强AM的细胞吞噬功能。     

Positive end-expiratory pressure modulates local and systemic inflammatory responses in a sepsis-induced lung injury model

OBJECTIVE: Previous animal studies have shown that certain modes of mechanical ventilation (MV) can injure the lungs. Most of those studies were performed with models that differ from clinical causes of respiratory failure. We examined the effects of positive end-expiratory pressure (PEEP) in the setting of a clinically relevant, in vivo animal model of sepsis-induced acute lung injury ventilated with low or injurious tidal volume. METHODS: Septic male Sprague-Dawley rats were anesthetized and randomized to spontaneous breathing or four different strategies of MV for 3 h at low (6 ml/kg) or high (20 ml/kg) tidal volume (V(T)) with zero PEEP or PEEP above inflection point in the pressure-volume curve. Sepsis was induced by cecal ligation and perforation. Mortality rates, pathological evaluation, lung tissue cytokine gene expression, and plasma cytokine concentrations were analyzed in all experimental groups. RESULTS: Lung damage, cytokine synthesis and release, and mortality rates were significantly affected by the method of MV in the presence of sepsis. PEEP above the inflection point significantly attenuated lung damage and decreased mortality during 3 h of ventilation with low V(T) (25% vs. 0%) and increased lung damage and mortality in the high V(T) group (19% vs. 50%). PEEP attenuated lung cytokine gene expression and plasma concentrations during mechanical ventilation with low V(T). CONCLUSIONS: The use of a PEEP level above the inflection point in a sepsis-induced acute lung injury animal model modulates the pulmonary and systemic inflammatory responses associated with sepsis and decreases mortality during 3 h of MV.     

Effects of blood volume and discontinuance of ventilation on pulmonary vascular pressures and blood gases in patients with low levels of positive end-expiratory pressure

Hypervolemic, normovolemic and hypovolemic patients with PEEP values less than 10 cm H2O were studied during brief discontinuance of mechanical ventilation to determine whether blood volume status would affect on-off ventilator pulmonary artery pressure (PAP) readings. There were no appreciable hemodynamic effects in patients with blood volume deficits less than one liter. Discontinuance for 1 min decreased PaO2 from 121 +/- 8 (SD) to 77 +/- 7 torr (p less than .001) and increased PaCO2 from 32 +/- 1 to 35 +/- 1 torr (p less than .01). The decreased PaO2 persisted up to one hour after return to mechanical ventilation. Our data reveal that brief discontinuance of ventilation in the normovolemic or hypervolemic patient with physiologic levels of PEEP does not increase the accuracy of PAP measurements. However, with severe hypovolemia, marked reductions in PAP may occur with discontinuance of mechanical ventilation. The practice of recording PAP off the ventilator and frequent suctioning of patients should be abandoned when interruption of mechanical ventilation has little utility and can result in persistent hypoxemia.     

High-frequency oscillatory ventilation does not decrease endothelin release in lung-lavaged rabbits

High-frequency oscillatory ventilation (HFO) has been shown to reduce lung injury and pulmonary arterial pressure (PAP). We hypothesized that HFO leads to decreased endothelin 1 (ET-1) and endothelin 3 (ET-3) release when compared to conventional mechanical ventilation (CMV) in lung-lavaged rabbits. DESIGN: Prospective, randomized, controlled animal study. In 26 adult New Zealand White Rabbits ventilated by CMV or HFO under hypoxemic and normoxemic conditions after lung lavage (CMV-hypo: n = 5; CMV-normo: n = 8; HFO-hypo: n = 7; HFO-normo: n = 6) we recorded systemic and PAP, measured blood gases, ET-1 and ET-3 and calculated intrapulmonary venous admixture during a 4-h experiment. ET-1 was significantly increased after lavage (p < 0.05) with no further increase until the end of the experiment. Neither pulmonary arterial nor systemic arterial ET-1 differed between CMV and HFO or between hypoxemia and normoxemia. Systemic arterial ET-3, however, was significantly higher in HFO-hypo than in the other two groups ventilated under normoxemic conditions at the end of the experiment (HFO-hypo vs. CMV-normo, p < 0.05; HFO-hypo vs. HFO-normo, p < 0.05). PAP showed a continuous increase in all groups (p < 0.05). We did not find any correlation between PAP and ET-1 or ET-3. Intrapulmonary venous admixture increased in animals ventilated under hypoxemic conditions, whereas it decreased after lung lavage in those ventilated under normoxemic conditions until the end of the experiment (HFO-normo, p < 0.05). CONCLUSIONS: This study suggests that HFO does not decrease ET-1 and ET-3 release compared to CMV in lung-lavaged rabbits. Hypoxemia, however, may increase ET-3 release from the lungs, leading to an increased intrapulmonary shunt.     

重度烟雾吸入致大鼠急性肺损伤的免疫应答及其机制探讨

目的分析重度烟雾吸入致吸人性急性肺损伤(ALI)对大鼠肺自然免疫及特异性免疫反应。方法分别复制一氧化碳(CO)浓度为2×10~(-3)(低浓度)和4×10~(-3)(高浓度)重度烟雾吸入致大鼠吸人性ALI模型。观察染毒后0～24 h大鼠肺组织病理学变化;检测支气管肺泡灌洗液(BALF)中致炎及抗炎细胞因子的浓度;用流式细胞仪检测外周血及BALF中淋巴细胞亚群数,BALF中CD45~+淋巴细胞和非淋巴细胞数量以及CD4~+/CD8~+变化。结果肺组织病理学检查证实染毒后可致明显肺损伤。染毒2 h BALF中肿瘤坏死因子-α(TNF-α)呈一过性升高,高浓度组较低浓度组更明显,之后下降;4 h白细胞介素-6(IL-6)、γ-干扰素(IFN-γ)开始升高,其中IL-6低浓度组较高浓度组明显,IFN-γ高浓度组较低浓度组明显,至12 h达高峰,24 h开始下降,但仍高于正常对照组水平(P＜0．05或P＜0．01);6～24 h IL-10与正常对照组比较均显著升高,尤以24 h明显(P＜0．05或P＜0．01)。外周血及BALF中CD4~+、CD8~+、自然杀伤细胞、B细胞及总T细胞均较正常对照组明显下降(P＜0．05或P＜0．01)。BALF中CD45~+淋巴细胞数和CD4~+/CD8~+均较正常对照组明显减少,非淋巴细胞数较正常对照组明显增多,且高浓度组较低浓度组变化趋势明显(P＜0．05或P＜0．01)。结论重度烟雾吸入致吸入性ALI的过程中伴有持续且过度的肺自然免疫反应,这种自然免疫反应部分由活化的中性粒细胞及巨噬细胞所介导;而肺特异性免疫反应受到明显的抑制。     

机械通气动态通气参数对急性呼吸窘迫综合征犬肺损伤的影响

目的观察机械通气动态通气参数对急性呼吸窘迫综合征(ARDS)犬肺损伤的影响,评价机械通气参数对肺损伤的保护作用。方法36条健康杂种犬,按照随机数字表法分为正常对照组(N组)、模型组(M组)及机械通气A～D组。采用气管内盐酸吸入法建立ARDS模型,按下述方案机械通气。A组:小潮气量(6ml/kg)、低吸气流速(6ml·kg-1·s-1)、高通气频率(30次/min);B组:大潮气量(20ml/kg)、高吸气流速(20ml·kg-1·s-1)、高通气频率(30次/min);C组:大潮气量(20ml/kg)、高吸气流速(17ml·kg-1·s-1)、低通气频率(15次/min);D组:大潮气量(20ml/kg)、低吸气流速(10ml·kg-1·s-1)、低通气频率(15次/min)。分组机械通气后0、1、2和4h各时间点分别记录呼吸力学各值。4h后处死动物,取肺脏测肺湿/干重(W/D)比值;光镜下观察病理组织学变化,并进行弥漫性肺泡损伤(DAD)评分及高倍镜下中性粒细胞计数;流式细胞仪检测肺组织核转录因子κB(NFκB)p65活性。结果B组肺W/D比值为9.95±0.99,高于A组6.78±0.56、D组7.11±0.47(P均<0.01),但与C组9.22±1.19差别不大(P>0.05)。肺组织病理DAD评分:B组为(12.80±1.47)分,明显高于A组(7.67±1.20)分和D组(8.83±1.17)分(P均<0.01),但与C组(11.50±1.87)分比较差异无显著性(P>0.05)。B组NFκBp65表达为(33.56±2.85)%,较A、D两组〔(10.35±0.60)%、(10.79±1.02)%〕表达增强(P均<0.01),与C组(30.87±1.16)%间比较差异无显著性(P>0.05)。结论大潮气量、高吸气流速、高通气频率机械通气可导致严重的呼吸机相关性肺损伤(VILI),降低通气频率可适当减轻这类损伤;在大潮气量基础上,降低通气频率及吸气流速,对损伤的肺组织可起到一定的保护作用。     

肺表面活性物质稀释剂延迟肺灌洗治疗烟雾吸入性损伤

目的 探讨外源性肺表面活性物质(PS)稀释剂延迟肺灌洗对大鼠严重烟雾吸入伤后内源性PS功能障碍和急性呼吸衰竭的治疗效果.方法 90只Wistar大鼠随机分为5组:Ⅰ组,正常对照(n=14);Ⅱ组,烟雾吸入(n=27);Ⅲ组,烟雾+PS灌洗+机械通气(MV),n=21;Ⅳ组,烟雾+盐水灌洗+MV,n=10;V组,烟雾+MV,n=18.伤后2 h经气管插管注入含PS(100ms/ks)的等渗盐水30 ml/kg或等量盐水行肺灌洗,MV 4 h,观察24 h;检测动脉血气、肺水量、静态肺顺应性(Cst)、支气管肺泡灌洗液(BAIF)蛋白含量、BALF表面张力特性和24 h病死率等.结果 致伤动物伤后立即出现严重缺氧和一氧化碳中毒;Ⅱ组发生急性呼吸衰竭、高通透性肺水肿和PS功能障碍;Ⅲ组Cst和BALF表面张力特性显著改善(P<0.05),但氧合能力、肺水量和BALF蛋白含量无明显好转(P>0.05).Ⅳ、V组疗效不佳.结论 外源性PS稀释剂延迟肺灌洗可一定程度恢复烟雾吸入所致内源性PS功能抑制,改善肺功能,但不能显著减轻高通透性肺水肿和呼吸衰竭,不能降低早期病死率.     

膨肺吸痰法在机械通气治疗中的应用和研究

目的探讨膨肺吸痰法在机械通气治疗中的应用和影响.方法将68例机械通气的重症患者随机分为两组,观察组34例采用膨肺吸痰法,对照组34例采用常规吸痰法.观察两组患者吸痰前后的血气分析值,并记录两组的机械通气时间、肺不张和肺部感染发生率.结果对照组吸痰前后动脉血氧分压、动脉血氧饱和度比较,差异有统计学意义(P＜0.05),观察组吸痰前后上述指标比较,差异无统计学意义(P＞0.05);比较两组机械通气时间(t＝2.840,P＜0.05)、肺不张发生率(x2＝4.570,P＜0.05)、肺部感染发生率(x2＝5.916,P＜0.05),差异均有统计学意义.结论膨肺吸痰法能改善机械通气患者吸痰时的低氧状况,并能缩短机械通气时间,降低肺不张、肺部感染发生率.     

Quality control of mechanical ventilation at the patient's home

OBJECTIVE: During home mechanical ventilation the prescribed settings are applied without permanent supervision of health professionals. After a long-time period of unattended operation at home the ventilator may not apply the ventilation parameters prescribed. This quality control study of home mechanical ventilation assessed whether tidal volume (V(T)), frequency (f), and minute ventilation (V'(E)) actually applied by the ventilator coincide with the values set on the ventilator control panel and with those prescribed. MEASUREMENTS: Actual V(T), f, and V'(E) applied by the ventilator in 30 patients on nocturnal HMV were measured at the patients' homes. The patients were subjected to volume targeted assist ventilation through nasal mask (n=28) or tracheostomy (n=2). The values of V(T), f, and V'(E) set at the ventilator were recorded. The actual and set V(T), f, and V'(E) values were compared with those prescribed. RESULTS: Considerable differences were found between actual, set and prescribed V(T), f, and V'(E). Actual V'(E) was significantly lower than V'(E) set: mean difference was 0.82 l/min, with considerable individual differences. Differences between actual and prescribed V'(E) were caused both by a poor performance of the ventilator and by a discrepancy between the values prescribed and those set at the ventilator control panel. CONCLUSIONS: Regularly assessing the actual performance of ventilators at the patient's home is a quality control procedure useful for detecting malfunctions which could improve compliance and outcome of home mechanical ventilation.     

中性粒细胞活化在呼吸机所致肺损伤中的作用

目的探讨中性粒细胞活化在呼吸机所致肺损伤中的作用。方法32只Wistar大鼠随机分为对照组、小潮气量组、常规潮气量组和大潮气量组。分别测定支气管肺泡灌洗液(BALF)中白细胞及中性粒细胞计数,血浆和BALF中蛋白含量及髓过氧化物酶(MPO)活性。结果常规潮气量组和大潮气量组大鼠BALF中白细胞及中性粒细胞计数、BALF中MPO活性和蛋白含量均明显高于对照组和小潮气量组(P<0.05或P<0.01),大潮气量组大鼠BALF中MPO活性和蛋白含量均明显高于常规潮气量组(P均<0.01),对照组和小潮气量组间比较差异均无显著性(P均>0.05)。各组大鼠间血浆MPO活性和蛋白含量比较差异均无显著性(P均>0.05)。结论中性粒细胞募集和活化在呼吸机所致肺损伤中起着重要作用,BALF中MPO活性是反映中性粒细胞活化程度的可靠指标,BALF中蛋白含量测定对评价肺损伤程度有实用价值。     

驱动压对肺内源性急性呼吸窘迫综合征的影响

目的探讨不同驱动压力对脂多糖诱导的肺内源性急性呼吸窘迫综合征（ARDS）的治疗作用及其机制。 方法40只雄性Sprague-Dawley大鼠分为对照组、急性呼吸窘迫综合征模型组（ARDS组）、机械通气低驱动压组（L组）、机械通气一般驱动压组（M组）、机械通气高驱动压组（H组）,每组各8只。气管内滴注脂多糖6 mg/kg复制ARDS动物模型,模型复制成功后对L组、M组及H组实施相应的机械通气策略4 h。比较5组大鼠动脉血氧分压（PaO₂）、二氧化碳分压（PaCO₂）、肺组织湿/干重比、肺泡灌洗液（BALF）中总蛋白、Ⅲ型前胶原（PCⅢ）、血清中白细胞介素6（IL-6）的表达水平以及肺组织病理形态学变化情况。 结果5组大鼠PaO₂、PaCO₂、肺组织湿/干重比、BALF中蛋白含量、血清IL-6、PCⅢ表达水平、塌陷肺泡所占比例以及膨胀肺泡所占比例比较,差异均有统计学意义（F= 25.054、5.316、14.306、84.940、93.379、41.983、49.343、123.433,P均< 0.05）。进一步两两比较发现,L组和H组PaO₂、肺组织湿/干重比、BALF中蛋白含量、血清IL-6以及塌陷肺泡所占比例与ARDS组比较,差异均有统计学意义（P均< 0.05）,H组PaCO₂表达水平和膨胀肺泡所占比例与ARDS组比较,差异均有统计学意义（P均< 0.05）,L组PCIⅢ表达水平较ARDS组显著降低（P < 0.05）;H组PaO₂、血清IL-6、PCⅢ表达水平、塌陷肺泡所占比例以及膨胀肺泡所占比例与ARDS组比较,差异均有统计学意义（P均< 0.05）。 结论在小潮气量通气下,较低的驱动压力能够改善脂多糖诱导的肺内源性ARDS大鼠的气体交换,减轻肺水肿,降低炎症反应;当驱动压过高时可能引起肺过度膨胀,甚至诱发肺损伤的发生。     

The effects of apparatus dead space on P(aCO2) in patients receiving lung-protective ventilation

BACKGROUND: Lung-protective ventilation using tidal volume (V(T)) of 4-6 mL/kg (predicted body weight) reduces mortality (compared with traditional V(T)) in patients with acute respiratory distress syndrome and acute lung injury. Standardized use of lower V(T) can result in respiratory acidosis and has raised new concerns about the appropriate configuration of the ventilator circuit, especially in regard to the dead space (V(D)) of the apparatus. We hypothesized that, with a patient receiving lung-protective ventilation, the removal of all apparatus dead space from the circuit would reduce P(aCO2) and allow a reduction in minute ventilation. METHODS: All the studied patients met the American-European consensus-conference criteria for acute respiratory distress syndrome/acute lung injury, were receiving a lung-protective ventilation strategy, were > 18 years of age, and were hemodynamically stable. We prospectively tested 3 different ventilator-circuit configurations, in random sequence, for 15 min each: (1) standard hygroscopic heat-and-moisture exchanger (HME) with 15-cm flexible tubing, (2) 15-cm flexible tubing only, (3) no HME or flexible tubing. V(T), respiratory rate, positive end-expiratory pressure, and fraction of inspired oxygen were maintained constant throughout the study, and exhaled CO2 was measured continuously. Physiologic dead space (V(D)/V(T)) was calculated using the Enghoff modification of the Bohr equation. RESULTS: Seven patients were studied. Removal of the HME from the circuit significantly decreased V(D)/V(T) (by approximately 6%) and P(aCO2) (by approximately 5 mm Hg). Removal of both the HME and flexible tubing from the circuit reduced V(D)/V(T) by an additional 5%, and P(aCO2) by an additional 6 mm Hg. With both circuit-configuration changes, minute ventilation fell from a mean of 11.51 L/min to 10.35 L/min, and pH increased from 7.30 to 7.38. Carbon-dioxide production did not change significantly. CONCLUSION: In patients receiving lower-V(T) ventilation, removing all the apparatus V(D) from the ventilator circuit reduces P(aCO2) and increases pH, at a lower minute ventilation. This information will help guide ventilator-circuit configuration for patients receiving lung-protective ventilation.     

肺保护性通气对肺内外源性急性呼吸窘迫综合征外周血和肺泡灌洗液中炎性介质影响的比较

目的　观察在肺保护性通气条件下急性呼吸窘迫综合征 (ARDS)模型犬氧合指数以及外周血和肺不同部位 (肺上区、肺下区腹侧和肺下区背侧 )支气管肺泡灌洗液 (BAL F)中炎性介质的变化。方法　健康雄性杂种犬 2 4只 ,随机分为肺内源性 ARDS(ARDSp)实验组、ARDSp 对照组、肺外源性 ARDS(ARDSexp)实验组和 ARDSexp对照组 ,每组 6只。采用静脉注射油酸形成 ARDSexp模型 ,应用十六烷磺基丁二酸钠盐气管内吸入形成 ARDSp模型。实验组肺损伤后进行肺保护性通气〔潮气量 8ml/ kg,呼气末正压(PEEP) 10 cm H2 O(1cm H2 O=0 .0 98k Pa)〕;对照组则继续进行大潮气量通气。动态观察肺保护性通气条件下 ARDS模型犬外周血和肺不同部位 (如肺尖叶、肺心叶和肺膈叶 ) BAL F中的炎性介质 ,如肿瘤坏死因子α(TNFα)、白细胞介素 (IL 1β,IL 6 )的变化。结果　肺损伤后 ARDS模型犬氧合指数均显著恶化 ,外周血中炎性介质明显升高 (P均 <0 .0 5 ) ,ARDSp模型犬肺尖叶和心叶 BAL F中炎性介质水平明显高于 ARDSexp模型犬 (P均 <0 .0 5 )。应用肺保护性通气治疗后 ,实验组犬氧合指数有不同程度改善 ,炎性介质水平有不同程度下降 ;但 ARDSp实验组的治疗效果不如 ARDSexp实验组。结论　 ARDSexp和 ARDSp的肺不同部位炎性介质释放和氧合     

雾化吸入布地奈德对肺泡灌洗液白介素-8、C-反应蛋白和前降钙素的影响

目的 探讨经口插管雾化吸入不同剂量布地奈德与静注地塞米松对慢性阻塞性肺病急性加重期(AECOPD)机械通气患者支气管肺泡灌洗液(BALF)中白介素-8(IL-8)、C-反应蛋白(CRP)和前降钙素原(PCT)的影响。方法 采用前瞻性、随机、对照研究设计,收集2008年1月至2010年9月绍兴市人民医院ICU符合2007年中华医学会呼吸病学分会慢性阻塞性肺疾病学组《慢性阻塞性肺疾病诊治指南》AECOPD机械通气患者共90例,在呼吸机支持、抗炎、化痰、扩张细支气管等常规治疗的基础上,随机(随机数字法)分为3组,分别给予布地奈德口插管内雾化吸入2 mg/d、4 mg/d和静注地塞米松2.5 mg q12 h。采用ELISA法测定三组患者在治疗初始、治疗3d以及治疗7d支气管肺泡灌洗液与血清IL-8、PCT和CRP值变化。所有数据均采用SPSS 13.0处理,组间分析采用方差分析,因素之间的相关性分析采用Pearson直线相关分析。结果 在治疗3,7d后,支气管肺泡灌洗液IL-8水平呈现不同程度下降,吸入布地奈德(4 mg/d)组＞吸入布地奈德(2 mg/d)组＞静滴地塞米松组,差异具有统计学意义(P＜0.05);血浆IL-8水平虽亦呈现相同趋势,三组在各时相点差异无统计学意义。CRP和PCT在支气管肺泡灌洗液和血浆无类似显著变化。治疗3,7d后支气管肺泡灌洗液IL-8水平与患者机械通气时间呈正相关。结论 通过口插管雾化吸入布地奈德与静注地塞米松相比,可较显著下调AECOPD机械通气患者支气管肺泡灌洗液IL-8水平,而对CRP和PCT的影响均不明显。支气管肺泡灌洗液IL-8水平或可作为评价AECOPD病情预后的一个指标。     

有创与无创序贯性机械通气治疗慢性阻塞性肺疾病所致呼吸衰竭的临床研究

目的探讨有创与无创序贯性机械通气在慢性阻塞性肺疾病（COPD）所致呼吸衰竭患者救治中的方法与疗效。方法对41例COPD呼吸衰竭患者进行气管插管并施行机械通气,出现HC窗后,随机分为序贯治疗组（21例）和对照组（20例）。序贯组治疗方法：出现PIC窗后,立即拔出气管插管,改用口鼻面罩双水平气道正压通气（BiPAP）。对照组治疗方法：出现HC窗后,继续按常规有创机械通气方法治疗,按临床常用压力支持通气（PSV）模式脱机。两组同时进行监护,观察两组患者VAP发生例数、有创通气时间、总机械通气时间、ICU监护时间、住院时间、住院费用和院内死亡例数。结果序贯组与对照组比较,VAP发生少,有创通气时间、总通气时间、ICU监护时间及住院时间短,住院费用减少（P〈0．05）,差异有统计学意义。结论在“肺部感染控制窗”指导下的有创一无创序贯性脱机治疗方法,可以明显降低VAP发病率,缩短机械通气,ICU和总住院时间,提高疗效,降低治疗费用,是具有一定临床实用价值的有效脱机方案。     

β-防御素-2在呼吸机相关性肺炎中的表达

目的观察机械通气大鼠铜绿假单胞菌(PA)肺部感染前后肺组织β防御素2(BD2)基因和蛋白质表达的变化,探讨肺组织BD2在呼吸机相关性肺炎(VAP)发生机制中的作用。方法58只健康清洁级雄性成年SD大鼠随机分为对照组和机械通气组。机械通气组大鼠采用经口气管插管机械通气24h后,经气管内注入PA复制肺部感染模型。对照组中大鼠无需机械通气,直接气管内接种PA复制肺部感染模型。采用逆转录聚合酶链反应(RTP-CR)和蛋白免疫印迹(Westernblot)技术测定大鼠BD2基因和蛋白质表达的变化。结果机械通气组重度肺组织病理变化大鼠占47.6%,明显高于对照组的28.5%(P<0.05)。机械通气组中BD2基因和蛋白质表达水平的上调在3h后显著低于对照组(P均<0.05)。机械通气组接种PA6h后血培养阳性率为40.0%,显著性高于对照组的6.7%(P<0.05)。机械通气组支气管肺泡灌洗液中PA培养阳性率持续为100.0%,而对照组从3h的100.0%降至24h的33.3%(P<0.05)。对照组存活率为80.0%,机械通气组为40.0%,两组比较,差异有显著性(P<0.05)。结论BD2基因和蛋白质表达上调水平的下降可能与VAP的发生和发展有关。