利多卡因-肺表面活性物质混合液对洗肺鼠呼吸衰竭的作用

目的　探讨利多卡因 (Li) 肺表面活性物质 (PS)混合液对洗肺鼠呼吸衰竭的作用。方法　 2 8只Wistar大鼠戊巴比妥钠腹腔内注射麻醉后 ,经气管切开孔插入导管行人工呼吸 ,吸气峰压(Ppeak)定为 1 4 7kPa ,吸呼比为 1∶1。将Ppeak及呼气末正压 (PEEP)分别调至 1 96kPa和 0 4 9kPa后 ,对所有动物行全肺灌洗 (生理盐水 3 7℃ ,4 0ml/kg) 8～ 10次。当动脉血氧分压 (PaO2 )降至 12kPa以下时 ,将动物随机分成四组 ,每组 7只。A组 :气管内注入Li( 2 5mg ,0 5ml) ;B组 :气管内注入PS( 2 5mg ,0 5ml) ;C组 :气管内注入PS( 2 5mg)与Li( 2 5mg)的混合液 0 5ml;D组 :气管内注入生理盐水 0 5ml。 12 0分钟后撤离PEEP ,并将Ppeak调至 1 4 7kPa ,测定动脉血气值、乳酸盐浓度及潮气量。结果　所有动物PaO2 经灌洗后由 5 5 0 7kPa降至 9 4 7kPa(P <0 0 5 )。治疗后A、B、C组的PaO2 均明显升高 (与灌洗后比较 ,P <0 0 5 ) ,以B、C组的升高显著 (恢复至灌洗前水平 ) ,但D组始终保持在8 8kPa以下。撤离PEEP后 ,A、B组PaO2 降至 18 8kPa以下 ,C组则一直维持在治疗后水平 (与其它三组比较 ,P <0 0 5 )。撤离PEEP后C组的乳酸盐浓度均低于其他三组 ,而平均动脉压明显高于其他三组。结论　Li PS混合液能改善洗肺鼠的呼     

肺表面活性物质及呼气末正压对呼吸衰竭的作用

目的　探讨肺表面活性物质 (PS)在不同呼气末正压 (PEEP)下对洗肺鼠呼吸衰竭的作用。方法　 5 6只Wistar大鼠 (体重 30 0～ 35 0 g)在戊巴比妥钠 (30mg/kg)腹腔内麻醉下人工呼吸并用生理盐水洗肺 ,共洗 8～ 11次 ,洗肺期间吸入峰压及PEEP分别调至 2 5cmH2 O和 7 5cmH2 O。当PaO2 降至 90mmHg以下时 ,随机分为八组 ,每组 7例。 1～ 4组经气道注入PS 2 5mg(0 5ml) ,5～ 8组则经气道注入等量的生理盐水 (0 5ml)。 1组和 5组的PEEP为 7 5cmH2 O ,2组和 6组的PEEP为5cmH2 O ,3组和 7组的PEEP为 2 5cmH2 O ,4组和 8组的PEEP为 0cmH2 O。结果　未注入PS的 5～ 8组的PaO2 在整个实验中未见明显变化 ,均在 10 0mmHg以下。注入PS的 1～ 4组中 ,无PEEP的第 4组及 2 5cmH2 OPEEP的第 3组的PaO2 未见明显改善 ,与 5～ 8组之间未见显著差异 (P >0 0 5 )。第 2组的PaO2 虽在注入PS后 15分钟明显升高至 (34 3 5 3± 132 2 6 )mmHg ,但以后逐渐下降至治疗前水平。只有第 1组的PaO2 在治疗后显著的升高至 40 0mmHg以上 (P <0 0 5 ) ,并维持此高值至实验结束。结论　单独PEEP不能改善洗肺鼠的低氧血症 ,补充PS并附加 7 5cmH2 O的PEEP可明显改善低氧血症     

肺表面活性物质对胎粪吸入鼠肺功能的影响

目的：探讨外源性肺表面活性物质（PS）对胎粪吸入鼠肺功能的影响。方法：28只Wistar大白鼠进行人工通气，经气道注入3－4ml/kg胎粪溶液，PaO2降至20kPa以下后将动物随机分为4组（每组7只）。A组，气道内注入PS 150mg/kg(50mg/ml,3ml/kg)；B组，气道内注入等量生理盐水；C组，用PS稀溶液75mg/kg(5mg/ml,15ml/kg)进行支气管肺泡灌洗，重复2次；D组，用15ml/kg的生理盐水灌洗双肺。治疗后15min,30min,60min,120min,180min采血进行血气分析。180min后测定各组潮气量，并进行支气管肺泡灌洗（BAL），检测BAL液中总蛋白（TP）和TNF－α含量。结果：治疗后A和C组PaO2均明显升高，而B和D组在治疗后几乎不变，A、C组与B、D组相比，P＜0．05。A与C组间差异均无显著性。A和C组的潮气量明显高于B和D组（P＜0．05）。A和C组的BAL液中TP含量明显低于B和D组（P＜0．05）。TNF－α含量各组间无差异。结论：补充PS明显改善胎粪吸入鼠肺的氧合和顺应性。PS稀溶液灌洗法优于气道注入法。     

肺表面活性物质替代疗法进展

肺表面活性物质（ＰＳ）替代疗法已广泛应用于新生儿呼吸窘迫综合征（ＲＤＳ）的临床治疗中，在ＡＲＤＳ和其它重症呼吸道疾病已见该疗法的成功应用。就近年来这方面的进展分制剂、给药途径及体内分布、剂量及时间、并发症、对内源性ＰＳ的影响、治疗效应及临床应用等作专项介绍。     

呼气末正压对外源性肺表面活性物质功能的影响

目的 探讨PEEP对外源性肺表面活性物质（PS）功能的影响。方法 用血清将PS稀释溶解配制成4.0、24 mg/ml的实验液体。同时将PS溶解于醋酸林格液中配成相同的浓度,作为对照。实验I:设定PEEP为 0,未成熟胎兔18只随机分为2组（每组9只）:A1组,经气道内注入溶解于醋酸林格液的PS24 mg/ml;B1组,注入溶于血清的PS24 mg/ml,实验Ⅱ设定PEEP为2.5cm H2O ,未成熟胎兔24只随机分为3组（每组8只）:A2组,经气道内注入溶解于醋酸林格液的 PS4.0 mg/ml;B2组,注入溶于血清的PS4.0 mg/ml;C2组未注入任何物质。人工通气后 5、10、15、20min测定动物潮气量。结果 人工通气 20 min时,A1组动物的潮气量大于15 ml/kg,而B1组小于8.0 ml/kg（P<0.05）;A2和B2组动物的潮气量均超过20 ml/kg,而 C2组小于2.0 ml/kg。结论PEEP可以增强PS的活性,拮抗血清对PS的抑制。     

急性呼吸窘迫综合征的肺表面活性物质替代治疗研究…

本文介绍了肺表面活性物质（ＰＳ）的组成，功能及其在急性呼吸窘迫综合征（ＡＲＤＳ）发病中的异常改变，并对外源性ＰＳ治疗ＡＲＤＳ的动物实验，临床儿及其对内源性ＰＳ的合成，分泌和功能的影响作了评价。     

肺泡表面活性物质肺灌洗治疗急性呼吸窘迫综合征

目的研究肺泡表面活性物质肺灌洗治疗急性呼吸窘迫综合征（ARDS）的效果。方法用12ml／kg 0．0225N的盐酸经气管注入新西兰白兔肺内,纯氧机械通气1h后,将符合PaO2／FiO2≤150mmHg的动物随机分成五组,每组5只。分别用生理盐水（Ⅰ组）、浓度为1g／L（Ⅱ组）、3g／L（Ⅲ组）、6g／L（Ⅳ组）、12g／L（Ⅴ组）的肺泡表面活性物质肺灌洗,灌洗容量为10ml／kg,观察每组治疗后的PaO2／FiO2的变化情况,并对肺标本行病理切片检查。结果Ⅰ组、Ⅱ组治疗后PaO2／FiO2没有改善,而Ⅲ组、Ⅳ组、Ⅴ组肺灌洗后PaO2／FiO2均显著改善,但这种效果随时间推移逐渐消失,病理切片显示Ⅲ组、Ⅳ组、Ⅴ组中肺泡间质充血水肿和肺泡腔渗出均较Ⅰ组、Ⅱ组明显减轻。结论采用浓度为3g／L以上的外源性肺泡表面活性物质对盐酸诱导的ARDS行肺灌洗有明显疗效,但效果不能持久。     

部分液体通气对急性肺损伤兔肺表面活性物质的影响

目的 研究部分液体通气(PLV)对油酸诱导的急性肺损伤肺表面活性物质的影响。方法 24只健康成年日本大白兔随机分成三组,每组8只:正常对照单纯机械通气组(C组);油酸肺损伤机械通气组(MV组)和油酸肺损伤部分液体通气组(PLV组)。中心静脉滴注油酸150μg/kg诱导急性肺损伤(ALI)模型,1h后当PaO_2/FiO_2<300时,认为造模成功,再连续通气4h,用多导生理监测仪连续记录血压和心率的变化,并测定基础、肺损伤及治疗后1、2、4h动脉血气。治疗4h立即处死动物,描记肺的压力-容积曲线,行右肺支气管灌洗,测量灌洗液中双饱和磷脂酰胆碱(DPPC)、肺表面活性物质相关蛋白A(SP-A)、总蛋白(TP)的浓度。结果 PLC组经PLV治疗后,PaO_2提高(P<0.01),各时段PaO_2高于MV组(P<0.01);PLV组PaCO_2逐渐降低,治疗后4h,PaCO_2与MV组差异有显著性(P<0.05)。PLV组灌洗液中DPPC、SP-A的含量高于MV组(P<0.01),而TP的含量低于MV组(P<0.01)。PLV组肺的顺应性较MV组提高。结论 PLV可增加油酸性急性肺损伤肺泡Ⅱ型上皮细胞分泌肺泡表面活性物质,改善肺功能。     

肺泡表面活性物质肺灌洗对急性呼吸窘迫综合征PaCO_2及PIP的影响

目的 研究肺泡表面活性物质肺灌洗治疗急性呼吸窘迫综合征(ARDS)的效果.方法 用12 ml/kg 0.0225 N的盐酸注入新两兰白兔气管内,纯氧机械通气1h后,将符合PaO_2/FiO_2≤150mm Hg的动物随机分成五组.每组5只.分别用生理盐水(NS组)、浓度为1 g/L(S_1组)、3g/l(S_3组)、6g/L(S_6组)、12g/L(S_(12)组)的肺泡表面活性物质肺灌洗.灌洗容量为10 ml/kg.观察治疗后的PaCO_2和气道吸气峰压(PIP)变化,并对肺标本行病理切片检查.结果 S_3组、S_6组、S_(12)组肺灌洗后PaCO_2明显改善,但效果不能持久.S_3组、S_6组、S_(12)组中肺泡间质允血水肿较NS组、S_1组明显减轻.结论 采用浓度为3g/L以上的外源性肺泡表而活性物质对盐酸诱导的ARDS行肺灌洗治疗可以改善肺通气,但效果不能持久.     

含氯胺酮的肺表面活性物质剂对洗肺鼠呼吸衰竭的作用

目的 探讨含氯胺酮的肺表面活性物质剂（ＰＳ）对洗肺鼠呼吸衰竭的作用。方法 ２０只Ｗｉｓｔａｒ大鼠经戊巴比妥钠腹腔内麻醉后,经气管切开孔插入导管行人工呼吸。吸气峰压（ＰＩＰ）定为１．４７ｋＰａ,呼吸比为１：１。将ＰＩＰ及呼气终末正压（ＰＥＥＰ）分别调至１．９６ｋＰａ和０．４９ｋＰａ后对所有动物行全肺灌洗（３７℃生理盐水,４０ｍｌ．ｋｇ＾－１）８～１０次。当动脉血氧分压（ＰａＯ２）降至１２ｋＰａ对下时     

The effects of multiple small doses of exogenous surfactant on experimental respiratory failure induced by lung lavage in rats

Aim: To test the effect on pulmonary gas exchange and mechanics of multiple small doses of exogenous surfactant as an alternative to bolus delivery in experimental respiratory failure induced by lung lavage.
Methods: After anesthesia, tracheostomy and constant volume ventilation, respiratory failure was induced by lung lavage in 20 rats. Animals were randomly assigned to an untreated control group or two experimental groups. Equal total doses of modified porcine surfactant (200 mg ·kg^-1 body weight,) were given by tracheal instillation, either as a single bolus or in four (50 mg·kg^-1 b.w.) fractional doses at 10-min intervals. Arterial pH and blood gases, and peak inspiratory pressure (PIP) were measured.
Results: After lavage, a rapid decrease in arterial pH and PaO₂, and an increase in PaCO₂ and PIP were observed in all animals. In both surfactant-treated groups, PaO₂ increased after surfactant instillation, and remained significantly higher than controls throughout the experiment. Arterial pH was significantly higher and PaCO₂ significantly lower only in the single bolus group. In the multiple dose group, these levels were similar to those of controls.
Conclusions: In surfactant-depleted rats with respiratory failure, instillation of four fractional surfactant doses did not result in the same enhancement on gas exchange and PIP, in the following 60 min, as same total dose given by a single bolus.     

急性呼吸窘迫综合征病人肺泡表面活性物质的变化

目的　研究患急性呼吸窘迫综合征 (ARDS)时病人肺泡表面活性物质的变化。方法　应用薄层色谱法测定ARDS早期病人 ( 5例 )和晚期病人 ( 5例 )肺泡灌洗液中肺泡表面活性物质 ,并和正常对照组 ( 5例 )作比较。结果　肺泡表面活性物质的含量在对照组、早期组、晚期组分别为6 7 6± 7 2、44 0± 7 3、31 3± 6 5 μg/ml肺灌洗液 ,呈递减改变。肺泡表面活性物质主要活性成份磷脂酰胆碱、磷脂酰甘油和二磷脂酰甘油的百分比在ARDS早期升高 ,分别达 5 6 2 %± 2 8%、9 2 %±1 5 %和 2 9%± 0 7%。在ARDS晚期 ,上述三种活性成份分别降至 39 7%± 5 2 %、5 6 %± 0 7%和 2 6 %± 0 6 %。结论　ARDS病人随着病情的进展加重 ,其肺泡表面活性物质的含量和主要活性成份逐渐减少。提示若使用外源性肺泡表面活性物质防治ARDS ,不仅要在数量上补足 ,而且需要恢复活性成份的比例 ,才有可能获得理想的疗效     

肺表面活性剂预防胃液误吸后急性呼吸衰竭的研究

目的：研究在误吸早期实施肺冲洗和肺表面活性物质替代疗法，对预防急性呼吸衰竭的作用。方法：在定压式人工呼吸条件下，经气管给大鼠肺内注入胃液（ｐＨ＝１．５）２．５ｍｌ／ｋｇ，造成误吸。然后将大鼠随机分为３组。Ｎ组及Ｓ组均在误吸３分钟后用生理盐水行支气管肺冲洗，其中Ｓ组在肺冲洗后立即注入肺表面活性剂。Ｇ组仅接受人工呼吸。结果：误吸后Ｇ组的动脉血气恶化，而Ｓ组由于应用了肺冲洗和肺表面活性剂有效地防止了急性呼吸衰竭的形成。单纯接受肺冲洗的Ｎ组血气没有得到改善。结论：应用此方法可以防止胃液误吸后急性呼吸衰竭的形成，降低死亡率。     

Aerosolized surfactant and dextran for experimental acute respiratory distress syndrome caused by acidified milk in rats

BACKGROUND: Inhibition of pulmonary surfactant by plasma-derived proteins is an important pathogenetic factor of acute respiratory distress syndrome (ARDS). Inhalation of aerosolized surfactant may be suitable for early treatment of ARDS. However, requirement of a high dose is a drawback. Because dextran reverses surfactant inhibition, we examined whether dextran improves the therapeutic effects of aerosolized surfactant in rats with experimental ARDS. METHODS: Acidified milk (pH 1.8, 1.5 ml kg(-1)) was injected into the trachea of the rats ventilated with pure oxygen using 2.45 kPa peak inspiratory pressure and 0.74 kPa positive end-expiratory pressure. When PaO2 decreased to <13 kPa, the rats were assigned to four groups: control group (n = 8), receiving no material; D-only group (n = 6), receiving aerosolized dextran for 45 min; S-only group (n = 8), receiving aerosolized modified natural surfactant (MNS) for 30 min; and S-plus-D group (n = 9), receiving aerosolized MNS for 30 min followed by aerosolized dextran for 15 min. RESULTS: In the control group and D-only groups, the mean PaO2 remained at <10 kPa for 180 min. In the S-only and S-plus-D groups, the PaO2 increased to 50 kPa (P < 0.01 vs. untreated). The PaO2 of the surfactant-only group gradually decreased to <17 kPa at 180 min, whereas the PaO2 of the S-plus-D group was maintained at >38 kPa for 180 min (P < 0.01 vs. S-only group). CONCLUSION: Inhalation of aerosolized dextran potentiates the effects of aerosolized surfactant by prolonging the therapeutic response.     

Effect of positive end-expiratory pressure on inflammatory response in oleic acid-induced lung injury and whole-lung lavage-induced lung injury

Purpose The present study investigated the effects of positive end-expiratory pressure (PEEP) on the inflammatory response in two different lung injury models: edematous lung induced by oleic acid (OA); and atelectatic lung induced by whole-lung lavage (LAV). Methods Japanese white rabbits (n = 28) were allocated to one of the two lung injury (OA or LAV) groups, and each group was treated with intermittent positive pressure ventilation, using zero end-expiratory pressure (ZEEP) or PEEP (1 cm H₂O above the lower inflection point [LIP]). Thus, the animals were divided into LAV-ZEEP, LAV-PEEP, OA-ZEEP, and OA-PEEP groups. Blood and bronchoalveolar lavage fluid (BALF) were sampled 3 h after ventilatory treatment to analyze interleukin (IL)-8 levels. Results Pa_{O 2} was significantly decreased after the induction of lung injury, but was significantly higher in the PEEP groups compared to the ZEEP groups for each lung injury. Serum IL-8 levels were elevated in both experimental models. Serum IL-8 levels were significantly lower in LAV-PEEP than in LAV-ZEEP, whereas no difference was noted between OA-PEEP and OA-ZEEP. BALF IL-8 levels were lower in LAV-PEEP than in LAV-ZEEP. PEEP above LIP attenuated the elevation of IL-8 in BALF and serum in atelectatic lungs, but did not attenuate these increases in the edematous lungs. Conclusion These results suggest that the protective effects of PEEP on injured lungs may depend on the underlying lung pathology.     

Aerosolized surfactant reverses respiratory failure in lung–lavaged rats

The effects of surfactant replacement by aerosol inhalation and by bolus instillation were compared in rats with respiratory failure induced by repeated lung lavage. The rats were anesthetized with pentobarbital sodium and mechanically ventilated with 100% oxygen. The Pao₂ of control rats not given surfactant (n = 9) remained below 13 kPa. A bolus instillation of a modified natural surfactant (75 mg kg^-1 b.w. in 1.5 ml–kg^-1 b.w. saline) into the airways rapidly reversed the respiratory failure; the mean Pao₂ value (n = 9) 15–180 min after instillation remained over 50 kPa ( P < 0.05 vs. controls). Inhalation of the aerosolized surfactant for 60 min through an ultrasonic nebulizer delivering 75 mg kg^-1 b.w. of the surfactant into the lungs gradually reversed the respiratory failure. The mean Pao₂ value (n = 9) 15 min after initiation of inhalation was 19.6 kPa (NS vs. controls), but after 60 min it rose to above 43 kPa ( P < 0.05 vs. controls; NS vs. bolus instillation). Treatment with surfactant either by continuous aerosol or by bolus led to significant increases of over 24% in the dynamic lung–thorax compliance. We conclude that aerosolized surfactant reverses respiratory failure induced by lung lavage, although the response is slower than after bolus instillation.