cav-1和TNF-α在机械通气联合高氧致大鼠ALI中的表达研究

目的 观察机械通气联合高氧对大鼠肺组织小窝蛋白1(cav-1)、核转录因子κB(NF-κB)和肿瘤坏死因子α(TNF-α)表达的影响,探讨机械通气联合高氧致大鼠ALI的发生机制及其相互作用.方法 24只雄性SD大鼠随机分为对照组、机械通气组和机械通气联合高氧组.观察各组大鼠肺组织的病理学改变,计算肺组织湿/干重比值;采用BCA法测定BALF中蛋白含量;采用免疫组化染色法和Western blot法测定肺组织中cav-1蛋白表达;采用RT-qPCR法测定肺组织中NF-κB和TNF-αmRNA表达.结果 与对照组比较,机械通气组和机械通气联合高氧组大鼠肺组织湿/干重比值、BALF中总蛋白含量以及肺组织中cav-1蛋白、NF-κB mRNA和TNF-αmRNA表达水平均显著升高(P值均<0.001),同时肺组织呈明显损伤性改变;机械通气组和机械通气联合高氧组之间上述指标比较差异也均有统计学意义(P值均<0.001),但机械通气组肺组织病理损伤程度较机械通气联合高氧组轻.相关性分析结果显示,各组大鼠肺组织cav-1蛋白表达量与NF-κB mRNA表达量之间呈正相关(r=0.827,P<0.001);NF-κB mRNA表达量与TNF-αmRNA表达量之间呈正相关(r=0.903,P<0.001).结论 高氧可上调肺组织cav-1的表达,使NF-κB信号通路发生活化,后者通过介导TNF-α等炎症细胞因子释放,从而加重机械通气大鼠肺组织炎症性损伤.     

死腔分数导向急性呼吸窘迫综合征呼气末正压选择的临床研究

目的 探讨早期急性呼吸窘迫综合征( ARDS)患者采用死腔分数法选择呼气末正压(PEEP)的可行性.方法 选23例机械通气的早期ARDS患者行持续肺膨胀手法充分肺复张,PEEP递减过程中分别采用最小死腔分数法、最大顺应性法、最佳氧合法选择最佳PEEP,观察不同方法选择的PEEP对患者氧合、解剖死腔容积(VD)/潮气容积(VT)、静态肺顺应性(CLst)和功能残气量(FRC)等的影响.结果 最小死腔分数法[(10.1±2.8)cm H2O(1 cm H2O =0.098 kPa)]和最大顺应性法[(11.3±2.5) cmH2O]选择的最佳PEEP间差异无统计学意义(P＞0.05),均明显低于最佳氧合法[(15.0±3.4) cm H2O,P＜0.05].最小死腔分数法选择PEEP机械通气时患者VD/VT(0.53±0.09)较基础状态(0.59±0.09)明显下降,但最大顺应性法和最佳氧合法选择的PEEP机械通气时VD/VT较基础状态未见明显变化.最小死腔分数法选择的PEEP,其氧合指数明显低于最佳氧合法[(288±123) mm Hg(1 mm Hg=0.133 kPa)比(356±119)mm Hg,P＜0.05],与最大顺应性法相比差异无统计学意义(P＞0.05),均高于基础状态.最小死腔分数法选择PEEP机械通气时气道平台压[(24±4) cm H2O]明显低于最大氧合法[(31±9) cm H2O].最佳氧合法选择的PEEP机械通气时的FRC明显高于最小死腔分数法和最大顺应性法.结论 采用最小死腔分数法选择的最佳PEEP,可改善ARDS患者氧合和CLst,减少死腔通气、降低气道平台压,是床边选择最佳PEEP的可行方法.     

肺保护性通气对急性呼吸窘迫综合征兔肺部炎症反应的影响

目的　观察肺保护性通气对急性呼吸窘迫综合征 (ARDS)家兔肺部炎症反应的影响。方法　生理盐水肺泡灌洗法复制ARDS家兔模型 ,将 36只家兔随机分为 6组 :(1)正常对照组 (N组 ) ,(2 )ARDS模型组 (M组 ) ,(3)小潮气量 (VT) 最佳呼气末正压 (PEEP)组 (A组 ) ,(4)常规VT 最佳PEEP组 (B组 ) ,(5 )小VT 高PEEP组 (C组 ) ,(6 )高VT 零PEEP组 (D组 )。机械通气 4h后测定肺组织湿/干重比 (W/D) ,迁移率改变电泳法 (EMSA)测定肺组织核因子κB(NF κB)活性 ,逆转录 聚合酶链反应(RT PCR)检测肺组织中肿瘤坏死因子α(TNF α)和白细胞介素 10 (IL 10 )mRNA表达 ,酶联免疫吸附测定 (ELISA)检测肺组织TNF α及IL 10浓度。结果　A组肺组织W/D为 5 6± 1 1,不但显著低于B组(6 6± 0 8)和D组 (6 9± 1 0 ) ,而且也显著低于C组 (6 6± 1 0 ,P均 <0 0 5 ) ,但与M组 (5 8± 0 5 )比较差异无显著性 (P >0 0 5 )。A组肺组织NF κB活性 (331± 113)显著低于B组 (45 5± 6 3)、C组 (478±74 )和D组 (6 4 5± 16 2 ,P均 <0 0 5 ) ,其中D组NF κB活性最高。与A组比较 ,B、C和D组肺组织TNF α及IL 10mRNA表达及浓度显著增高 ,其中D组TNF α和IL 10mRNA表达及其浓度在各组中最高。肺组织髓过氧化物酶 (MPO)及丙二醛 (MDA)含     

大鼠呼吸机相关肺损伤自噬相关蛋白的表达及意义

目的探讨大鼠呼吸机所致肺损伤(VILI)过程中自噬相关蛋白的表达及意义。方法健康雄性SPF级SD大鼠30只,7周龄,体重(220±20)g,实施麻醉和气管切开术后分别接受不同潮气量(VT)的通气(通气时间均为4 h)。随机分为三组:对照组(A组,仅切开气管保留自主呼吸);常规通气组(B组,VT=10 ml/kg);损伤通气组(C组,VT=40 ml/kg)。A组在气管切开即刻,其他组在机械通气结束后放血处死动物,Western印迹检测肺组织Beclin1和LC3的表达,计算肺湿/干比重(W/D比值)、MPO活性及肺泡灌洗液中总蛋白含量,光镜下行白细胞计数。结果在大潮气量机械通气4 h后,肺组织中总蛋白、W/D、白细胞计数和MPO等指标均显著增加(P0.05);肺组织中Beclin1、LC3表达水平(1.21±0.11、0.91±0.11)均显著增加。结论自噬表达的增加参与了大鼠VILI的发生。     

两种通气策略对老年人腹部手术中肺顺应性及外周血IL-6和IL-8的影响

目的探讨两种通气策略(低潮气量+小PEEP机械通气及常规大潮气量)对老年病人腹部手术短期机械通气肺外周血白细胞介素-6(IL-6)、白细胞介素-8(IL-8)的影响。方法选择腹部择期手术的老年患者(年龄60岁,ASAⅠ～Ⅱ级)40例,根据机械通气方式不同,随机分为两组。LV+P组(A组):低潮气量+小PEEP(呼气末正压),潮气量(VT)为7 ml/kg PBW(预测体重),PEEP为5 cmH2O;常规大潮气量组(B组),VT 12 ml/kg PBW,PEEP为0。分别于气管插管后机械通气5 min、3 h这2个时点,采集静脉血测定血清IL-6、IL-8浓度。结果两组肺顺应性(CL)均随着时间延长呈下降趋势,B组明显低于A组(P0.01)。机械通气3 h时A组肺外周血IL-6、IL-8增加量较B组明显降低(P=0.000,P=0.002)。结论在老年病人腹部手术中低潮气量加小PEEP机械通气与常规大潮气量均可引起老年病人血浆IL-6和IL-8水平升高,肺顺应性降低,但低潮气量加小PEEP可以减轻该变化。     

高容量通气对兔肺组织肿瘤坏死因子-α、白介素-1β、转化生长因子-β1表达的作用

目的:探讨高容量机械通气对大白兔肺组织TNF-α、IL-1β、TGF-β1的作用.方法:将30只3月龄雄性大白兔随机分成3组:对照组、常规潮气量组及大潮气量组,每组各10只.对照组插管后不机械通气,另2组插管后机械通气.常规潮气量组VT8 mL/kg,大潮气量组VT 25 mL/kg,其它参数相同,通气时间24 h.观察实验前后动脉血pH值、PaO2及PaCO2的变化、ELISA法测定肺组织TNF-α、IL-1β,SABC法测定TGF-β1、测定肺组织湿/干重(W/D)值、观察肺组织病理学变化.结果:与对照组比较,大潮气量组通气24 h后动脉血pH、PaO2和PaCO2变化显著(均P＜0.05),肺组织W/D、TNF-α、IL-1β、TGF-β1升高(均P＜0.01),肺组织水肿,常规潮气量组相应指标无显著变化(P＞0.05).结论:大潮气量机械通气易发生呼吸机相关性肺损伤(VILI),表现为动脉氧分压、肺组织W/D、肺组织病理变化,同时肺组织TNF-α、IL-1β、TGF-β1升高,表明VILI与TNF-α、IL-1β、TGF-β1炎性细胞因子有关.     

低潮气量低呼气末正压治疗急性肺创伤术后急性呼吸窘迫综合征疗效观察

目的 :探讨急性肺创伤术后并发急性呼吸窘迫综合征 (ARDS)患者的机械通气对策 ;方法 :将6 1例急性肺创伤术后并发ARDS患者随机分为A、B两组 ,A组 31例 ,采用传统机械通气模式 (VT10～ 13.5ml/kg ,PEEP 10～ 18cmH2 O) ;B组 30例 ,采用低潮气量、低呼气末正压 (VT7～ 8ml/kg ,PEEP 5～ 10cmH2 O)、许可性高碳酸血症通气 (动脉血PaCO2 10 .18± 1.14kPa ,pH 7.30±0 .0 5 )对策。通过调节同步间歇指令通气频率使两组患者的分钟通气量保持对等 (9～ 12L/min) ,对两组患者进行疗效比较。结果 :A组病死率和机械通气所致并发症发生率均明显高于B组 (P<0 .0 5或 <0 .0 1)。结论 :低VT、低PEEP机械通气对策可明显降低急性肺创伤术后并发ARDS患者的病死率。     

单肺通气模式下不同水平PEEP对肺损伤的影响

目的探讨单肺通气模式下不同水平呼气末正压通气(PEEP)对肺损伤的影响。方法选择拟单肺通气剖胸手术患者60例,随机分成三组,每组20例。A组单肺通气6 mL/kg+PEEP为0 cmH2O,B组单肺通气6mL/kg+PEEP为4 cmH2O,C组单肺通气6 mL/kg+PEEP为8 cmH2O,术中均为持续性单肺通气,并排除肺功能差或有肺部疾病者。通过监测单肺通气前(T1)、单肺通气30 min(T2)、单肺通气60 min(T3)、单肺通气90 min(T4)、单肺通气结束前(T5)、出室前(T6)的SpO2、MAP、HR。采集颈内静脉血5 mL进行肿瘤坏死因子(TNF-α)、IL-6检测。结果三组治疗不同时间点MAP、HR、SpO2无统计学差异(P均>0.05)。B、C两组从T3开始相对于A组炎性因子水平较低且有统计学差异(P均<0.05),而B、C两组间炎性因子水平比较无统计学差异(P均>0.05)。结论单肺通气6 mL/kg+PEEP 4 cmH2O对肺损伤影响最小。     

核因子κB在呼吸机致急性肺损伤大鼠肺组织巨噬细胞炎症蛋白-1α表达中的作用

目的 通过观察不同潮气量机械通气大鼠肺组织核因子κB(NF κB)p65蛋白和巨噬细胞炎症蛋白-1 α(MIP-1α)mRNA表达水平,探讨NF-κB活化对呼吸机致急性肺损伤大鼠肺组织MIP-1α表达的调控作用.方法 24只雄性健康Wistar大鼠随机分为对照组、小潮气量组和大潮气量组.分别采用原位杂交和免疫组织化学染色法检测各组大鼠肺组织MIP-1α mRNA及NF-κB p65蛋白的表达水平.结果 大潮气量组大鼠肺组织细支气管上皮NF-κB p65蛋白和MIP-1α mRNA阳性表达细胞百分比均明显高于小潮气量组和对照组(P值均<0.01).对照组与小潮气量组比较差异无统计学意义.相关性分析结果表明,各组大鼠细支气管上皮NF-κB p65蛋白阳性表达细胞百分比与MIP-1α mRNA阳性表达细胞百分比之间呈正相关(r=0.482,P<0.05).结论 大潮气量机械通气引发肺组织MIP-1α mRNA高表达在呼吸机所致肺损伤发生中具有一定作用,肺组织MIP 1α表达在一定程度上可能受NF-κB的调控.     

肺复张后呼气末正压通气不同模式对腹腔镜结直肠癌根治术肥胖患者呼吸力学和血流动力学的影响

目的探讨肺复张后呼气末正压通气(PEEP)不同模式对腹腔镜结直肠癌根治术肥胖患者呼吸力学和血流动力学的影响。方法 90例拟行腹腔镜结直肠癌根治术肥胖患者随机分为传统组、PEEP5组和PEEP10组,设置潮气量(VD)8 ml/kg,分别在肺复张后不给予PEEP、PEEP 5 cm H2O和PEEP 10 cm H2O。观察气腹建立前(T0)、气腹建立后10 min(T1)、气腹后头低足高位20 min(T2)和气腹结束(T3)时的气道峰压(Ppeak)、平台压(Pplat)、有效静态总顺应性(Cst)、气道阻力(Raw)、氧合指数(PaO_2/FiO_2)、死腔量(VD/VT)和肺内分流量。结果与传统组比较,PEEP5组和PEEP10组T1时Ppeak、Raw、VD/VT和Qs/Qt增加,Cst和PaO_2/FiO_2下降,T2和T3时VD/VT和Qs/Qt下降,PaO_2/FiO_2增加(P<0.05);与PEEP5组比较,PEEP10组T3时Ppeak、VD/VT和Qs/Qt下降,PaO_2/FiO_2增加(P<0.05)。结论肺复张后给予小VD(8 ml/kg)+PEEP可以改善腹腔镜结直肠癌根治术肥胖患者呼吸力学和血流动力学指标,且PEEP 10 cmH2O效果更优。     

A decremental PEEP trial for determining open-lung PEEP in a rabbit model of acute lung injury

A positive end-expiratory pressure (PEEP) above the lower inflection point (LIP) of the pressure-volume curve has been thought necessary to maintain recruited lung volume in acute lung injury (ALI). We used a strategy to identify the level of open-lung PEEP (OLP) by detecting the maximum tidal compliance during a decremental PEEP trial (DPT). We performed a randomized controlled study to compare the effect of the OLP to PEEP above LIP and zero PEEP on pulmonary mechanics, gas exchange, hemodynamic change, and lung injury in 26 rabbits with ALI. After recruitment maneuver, the lavage-injured rabbits received DPTs to identify the OLP. Animals were randomized to receive volume controlled ventilation with either: (a) PEEP = 0 cm H2O (ZEEP); (b) PEEP = 2 cm H2O above OLP (OLP + 2); or (c) PEEP = 2 cm H2O above LIP (LIP + 2). Peak inspiratory pressure and mean airway pressure were recorded and arterial blood gases were analyzed every 30 min. Mean blood pressure and heart rate were monitored continuously. Lung injury severity was assessed by lung wet/dry weight ratio. Animals in OLP + 2 group had less lung injury as well as relatively better compliance, more stable pH, and less hypercapnia compared to the LIP + 2 and ZEEP groups. We concluded that setting PEEP according to the OLP identified by DPTs is an effective method to attenuate lung injury. This strategy could be used as an indicator for optimal PEEP. The approach is simple and noninvasive and may be of clinical interest.     

Effect of PEEP on the arterial minus end-tidal carbon dioxide gradient

The effect of PEEP on the arterial minus end-tidal carbon dioxide gradient (PaCO2-PetCO2) was evaluated in 13 adult patients with acute respiratory failure. The morphologic study of the pressure-volume (P-V) curves allowed separation of the patients into two groups: group 1 (n = 7) with initial inflection point in the (P-V) curve, and group 2 without inflection point. We hypothesized that the profile of the PaCO2-PetCO2 gradient would indicate an appropriate PEEP level only in patients with recruitable air spaces. We ventilated group 1 patients with zero end expiratory pressure (ZEEP), PEEP corresponding to inflection point pressure (PEEPPi) and PEEP5 cm H2O above PEEPPi, and group 2 patients with ZEEP, 6 cm H2O PEEP and 12 cm H2O PEEP. The PaCO2-PetCO2 gradient changed significantly in group 1 (ZEEP: 13.59 mm Hg; PEEPPi: 8.33 mm Hg; PEEPPi + 5 cm H2O: 10.54 mm Hg), but not in group 2 (ZEEP: 14.15 mm Hg; PEEP 6 cm H2O: 14.20 mm Hg; PEEP 12 cm H2O: 16.53 mm Hg). Our results show that the PaCO2-PetCO2 gradient may be useful in selecting a PEEP level which produces alveolar recruitment, but only in those patients with initial inflection point in the P-V curve.     

Effects of PEEP on respiratory mechanics after open heart surgery.

Respiratory dysfunction, particularly atelectasis, is common after open heart surgery. Routine use of PEEP (5 to 10 cm H2O) in these patients has been advocated. We studied the effects of different levels of PEEP on respiratory mechanics in ten mechanically ventilated open heart surgery patients in the immediate postoperative period. PEEP was studied in increasing increments and decreasing decrements. This procedure was repeated three times. Flow, tidal volume, and airway pressure were measured. We used the rapid airway occlusion technique to determine static compliance of the respiratory system (Cst,rs) and intrinsic PEEP (PEEPi). The changes in end-expiratory lung volume (delta EELV) were measured with respiratory inductive plethysmography. Recruitment of lung units (Vrec) was estimated as the difference in lung volume between PEEP and zero end-expiratory (ZEEP) for the same static inflation pressure (15 cm H2O). We found that (1) Cst,rs at ZEEP was significantly reduced (60 +/- 2 ml/cm H2O); (2) while PEEP of 5 cm H2O did not cause significant recruitment, higher levels of PEEP (10 to 15 cm H2O) were effective; (3) Cst,rs, Vrec, and delta EELV were higher during stepwise PEEP decrease; (4) after the first and second stepwise PEEP increase-decrease run, there was a small persistent increase in EELV and Cst,rs at ZEEP. No further changes were found after the third run. We conclude that after open heart surgery, PEEP less than 10 cm H2O is not effective to reopen atelectatic lung units.     

Alveolar instability causes early ventilator-induced lung injury independent of neutrophils

Intratracheal instillation of Tween causes a heterogeneous surfactant deactivation in the lung, with areas of unstable alveoli directly adjacent to normal stable alveoli. We employed in vivo video microscopy to directly assess alveolar stability in normal and surfactant-deactivated lung and tested our hypothesis that alveolar instability causes a mechanical injury, initiating an inflammatory response that results in a secondary neutrophil-mediated proteolytic injury. Pigs were mechanically ventilated (VT 10 cc/kg, positive end-expiratory pressure [PEEP] 3 cm H2O), randomized to into three groups, and followed for 4 hours: Control group (n = 3) surgery only; Tween group (n = 4) subjected to intratracheal Tween (surfactant deactivator causing alveolar instability); and Tween + PEEP group (n = 4) subjected to Tween with increased PEEP (15 cm H2O) to stabilize alveoli. The magnitude of alveolar instability was quantified by computer image analysis. Surfactant-deactivated lungs developed significant histopathology only in lung areas with unstable alveoli without an increase in neutrophil-derived proteases. PEEP stabilized alveoli and significantly reduced histologic evidence of lung injury. Thus, in this model, alveolar instability can independently cause ventilator-induced lung injury. To our knowledge, this is the first study to directly confirm that unstable alveoli are subjected to ventilator-induced lung injury whereas stable alveoli are not.     

Surfactant treatment for ventilation-induced lung injury in rats: effects on lung compliance and cytokines

The objective of this study was to determine if exogenous surfactant therapy could prevent the harmful effects of ventilation at high tidal volumes without positive end-expiratory pressure (PEEP). Rats were randomized to either a nontreated control group (8 mL/kg 4 cm H2O PEEP), a nontreated injuriously ventilated group (20 mL/kg 0 cm H2O PEEP) or a treatment group of either 50 mg/kg, 50 mg/kg + 5% surfactant-associated protein A, 100 mg/kg exogenous surfactant followed by injurious ventilation. Isolated lungs from animals in all 5 groups were ventilated in a humidified box at 37 degrees C for 2 hours. Pressure-volume curves and light microscopy showed that surfactant treatment reduced the ventilation-induced lung injury (VILI). Inflammatory cytokines (tumor necrosis factor-alpha [TNFalpha], interleukin [IL]-1beta, and IL-6) in the lavage were significantly higher in injuriously ventilated lungs compared to the control group. However the 3 treatment groups had cytokine concentrations that were similar to the injuriously ventilated group. We conclude that surfactant treatment is beneficial in preventing VILI; however, it does not prevent the release of inrflammatory cytokines during mechanical ventilation.     

分侧肺通气时不同呼气末正压和潮气量对单侧肺损伤犬循环的影响

目的 观察不同步分侧肺通气和同步分侧肺通气对单侧急性肺损伤(ALI)犬循环的影响.方法 取健康杂种犬12只,建立盐酸所致单侧肺损伤动物模型,行容积控制通气,将犬按随机数字表法分为不同步分侧肺通气组(NS组)和同步分侧肺通气组(S组).参数:患侧潮气量3.5 ml/kg保持不变,呼气末正压(PEEP)选择15、20、25 cm H2O(1 cm H2O=0.098 kPa);患侧PEEP 10 cm H2O不变,潮气量用随机数字表法选择5、7.5、10 ml/kg.健侧通气参数始终不变,检测不同通气条件下两组犬血流动力学和氧动力学指标.结果 (1)患侧潮气量3.5 ml/kg不变,PEEP为15、20 cm H2O时,两组血流动力学和氧动力学参数差异无统计学意义.当患侧PEEP为25 cm H2O时,NS组心率、体循环平均压(mABP)、心输出量、氧合指数和混合静脉血氧饱和度(SvO2)分别为(98±8)次/min、(84±6)mm Hg(1 mm Hg=0.133 kPa)、(1.10±0.13)L/min、(199±14)mm Hg和(55±6)%,明显低于S组[分别为(124±9)次/min、(103±7)mm Hg、(1.52±0.28)L/min、(221±15)mm Hg和(62±4)%,t值分别为-7.852、-16.561、-15.043、-13.314和-5.653,均P＜0.01].(2)患侧PEEP 10 cm H2O不变,潮气量分别为5、7.5 ml/kg时,两组的血流动力学和氧动力学参数比较差异无统计学意义.当患侧潮气量为10 ml/kg时,NS组HR、mABP、心输出量、氧合指数和SvO2均低于S组(均P＜0.01).结论 在本实验动物模型中,患侧与健侧所用PEEP水平相差≤20 cm H2O或患侧潮气量≤7.5 ml/kg时,同步和非同步分侧肺通气均能保持循环稳定.若需要更高水平PEEP时,建议选用同步分侧肺通气.     

Positive end-expiratory pressure after a recruitment maneuver prevents both alveolar collapse and recruitment/derecruitment

We tested the hypothesis that collapsed alveoli opened by a recruitment maneuver would be unstable or recollapse without adequate positive end-expiratory pressure (PEEP) after recruitment. Surfactant deactivation was induced in pigs by Tween instillation. An in vivo microscope was placed on a lung area with significant atelectasis and the following parameters measured: (1) the number of alveoli per field and (2) alveolar stability (i.e., the change in alveolar size from peak inspiration to end expiration). We previously demonstrated that unstable alveoli cause lung injury. A recruitment maneuver (peak pressure = 45 cm H2O, PEEP = 35 cm H2O for 1 minute) was applied and alveolar number and stability were measured. Pigs were then separated into two groups with standard ventilation plus (1) 5 PEEP or (2) 10 PEEP and alveolar number and stability were again measured. The recruitment maneuver opened a significant number of alveoli, which were stable during the recruitment maneuver. Although both 5 PEEP and 10 PEEP after recruitment demonstrated improved oxygenation, alveoli ventilated with 10 PEEP were stable, whereas alveoli ventilated with 5 PEEP showed significant instability. This suggests recruitment followed by inadequate PEEP permits unstable alveoli and may result in ventilator-induced lung injury despite improved oxygenation.     

Alveolar derecruitment at decremental positive end-expiratory pressure levels in acute lung injury: comparison with the lower inflection point, oxygenation, and compliance.

We examined the hypothesis that recording multiple elastic pressure-volume (Pel/V) curves and calculating alveolar derecruitment (V(DER)) induced by decreasing positive end-expiratory pressure (PEEP) may allow determination of alveolar closing pressures, thus helping to select the optimal PEEP level. V(DER) measured in 16 patients with acute lung injury (ALI) was compared with the lower inflection point (LIP) and oxygenation changes. A modified automated method was used to record multiple Pel/V curves at low constant flow. PEEP was decreased in 5-cm H(2)O steps, from 20 or 15 cm H(2)O to 0 cm H(2)O (ZEEP). V(DER) was the volume loss between the curves recorded from PEEP and from ZEEP at the same Pel. Derecruitment occurred at each PEEP decrement, being spread almost uniformly over the 20/15 to 0 cm H(2)O range. V(DER) was not correlated with LIP. V(DER) changes correlated with Pa(O(2))/FI(O(2)) changes (rho = 0.6, p = 0.02). Linear compliance at ZEEP was correlated to V(DER) at PEEP 15 cm H(2)O (rho = 0.9, p = 0.001), suggesting that compliance above LIP may reflect the amount of recruitable lung. Thus, alveolar closure in ALI occurs over a wide range of pressures, and LIP is a poor predictor of alveolar closure.     

脑肠肽 Ghrelin 对呼吸机相关性肺损伤大鼠的保护作用机制研究

目的：研究脑肠肽 Ghrelin 预处理对呼吸机相关性肺损伤大鼠的保护作用及机制。方法36只雄性 Sprague-Dawley 大鼠,体质量(300±20)g,随机分为3组(n =12);对照组;呼吸机相关性肺损伤组(VILI)组;Ghrelin 预处理组。其中对照组给予常规机械通气(通气设置：潮气量10 ml/kg,频率40次/分,吸入氧浓度21%),VILI 组和 Ghrelin 预处理组给予高潮气量机械通气(通气设置：潮气量30 ml/kg,频率40次/分,吸入氧浓度21%)。Ghrelin 预处理组在行机械通气前30 min 皮下注射50 ng/kg Ghrelin,对照组和 VILI 组于机械通气前30 min 皮下注射等体积生理盐水;所有动物在机械通气4 h 后处死,取肺组织,光镜检查病理改变,计算肺湿干比重及检测组织髓化过氧化物酶(MPO)水平,收集 BALF,检测总蛋白总量和炎性因子肿瘤坏死因子α(TNF-α)和 IL-6的水平,取血液标本行血气分析并计算氧合指数(PaO 2/FiO 2)。结果光镜下可见：同对照组相比, VILI 组肺组织病理损伤严重,BALF 中蛋白总量及炎性因子 TNF-α和 IL-6水平明显升高(P 值均<0.05),肺组织湿干比及 MPO 水平明显升高(P <0.05),氧合指数明显降低(P <0.05)。而经Ghrelin 处理后的 VILI 大鼠肺组织病理学改变明显减轻,BALF 中蛋白总量及细胞计数均较 VILI 组明显降低,氧合指数明显改善(P <0.05)。结论皮下注射脑肠肽 Ghrelin 可降低呼吸机相关性肺损伤,其主要作用机制是通过抗炎而发挥保护作用的。     

Positive end-expiratory pressure preserves surfactant function in preterm lambs.

Ventilation style influences lung injury and the amount of large-aggregate biophysically active surfactant in adult lungs. We asked how positive end-expiratory pressures (PEEP) would influence clinical responses and surfactant pools in surfactant-treated preterm lambs ventilated for 7 h with tidal volumes (VT) of 10 ml/kg. The 126-d gestation preterms were delivered and treated with 100 mg/kg recombinant human surfactant protein C (rSP-C) containing surfactant and ventilated with zero, 4, or 7 cm H(2)O of PEEP. A comparison group was treated with natural sheep surfactant and ventilated with zero PEEP. Physiologic measurements were similar for lambs treated with rSP-C surfactant and natural surfactant. PEEP 4 and 7 improved oxygenation and compliance relative to either group of lambs ventilated with PEEP zero. The maximal lung volumes measured at 40 cm H(2)O pressure after 7 h ventilation for the PEEP 4 and 7 groups were more than double those measured for either PEEP zero group. Alveolar surfactant pools were larger for the PEEP 7 group, and the large-aggregate fraction was increased for the PEEP 4 and 7 groups, resulting in large-aggregate pool sizes that were 3-fold higher for the PEEP 4 and 4-fold higher for the PEEP 7 groups relative to the PEEP zero group treated with rSP-C surfactant. All large-aggregate surfactants lowered minimal surface tensions of a captive bubble to less than 5 mN/m. In preterm surfactant-treated lambs PEEP improved lung function and maintained more of an rSP-C surfactant in the biophysically active form.