乌司他丁对脓毒症大鼠肺损伤的保护作用

目的探讨乌司他丁(UTI)对脓毒症性急性肺损伤(ALI)的保护作用。方法采用盲肠结扎穿孔(CLP)制作SD大鼠脓毒症ALI模型,随机分ALI组、糖皮质激素(GC)治疗(GC)和UTI治疗(UTI)组。成模后3 h、6 h、12 h开腹抽血行动脉血气分析,提取支气管肺泡灌洗液(BALF)检测总蛋白(TP)、总磷脂(TPL)、饱和磷脂酰胆碱(DSPC)含量,测定肺组织湿/干重(W/D)比值和肺组织匀浆中髓过氧化物酶(MPO)、丙二醛(MDA)含量,血浆中肿瘤坏死因子(TNF-α)、白介素-6(IL-6)含量,观察与比较各组肺组织病理改变。结果UTI组PaCO_2、PaO_2、HCO_3~-、BE与GC组差异无统计学意义(P＞0．05),但高于ALI组(P＜0．05);两组W/D均明显低于ALI组(P＜0．01),BALF中TP显著低于ALI组(P＜0．01),TPL和DSPC/TPL高于ALI组(P＜0．05、P＜0．01),但两组间差异无统计学意义(P＞0．05);两组肺组织匀浆中MPO、MDA含量均明显低于ALI组(P＜0．01),UTI组MPO含量还明显高于GC组(P＜0．05);两组血浆TNF-α、IL-6水平均低于ALI组(P＜0．01),UTI组IL-6高于GC组(P＜0．05);两组病理变化均较ALI组轻(P＜0．01)。结论UTI能改善缺氧、过度通气和酸中毒,减轻肺水肿和肺组织病理损伤,具有抗氧化和抑制炎性细胞因子释放作用,其抗炎作用与GC相似。     

乌司他丁对体外循环过程中肺保护作用的影响

目的体外循环导致急性肺损伤，本研究在体外循环过程中应用乌司他丁后观察肺组织损伤程度的变化，及探讨肺损伤与丝裂原激活蛋白激酶（MAPK）的变化规律的关系。方法100例风湿性心脏病行二尖瓣人工机械瓣置换的病人分为Ⅰ、Ⅱ组。Ⅰ组50例，行常规体外循环，心脏阻断40—55分钟，术中持续肺灌注低温氧合机器血；Ⅱ组50例，体外循环方法同Ⅰ组，在Ⅱ组术中用乌司他丁加低温氧合机器血行肺灌注；分别在不同时段取二组病人血液标本，测量P38MAPK活性，炎症细胞因子IL-6、ID8，及术后气道峰值压力、氧指数等。结果Ⅰ组P38MAPK活性明显增高，Ⅰ组肺损伤与Ⅱ组相比加重（出现统计学差异）。结论体外循环过程中，抑制P38MAPK活性表达可减轻肺损伤，术中应用乌司他丁肺灌注有抑制肺损伤的作用，为体外循环术中肺保护提供一种切实可行的方法。     

经肺动脉持续灌注低温含氧血及乌司他丁对肺的保护作用

目的:观察持续肺动脉灌注低温含氧血混和乌司他丁对肺功能的保护作用。方法:130例瓣膜病患者随机分为肺保护组70例,对照组60例。肺保护组在升主动脉阻断后,经主肺动脉持续灌注低温含氧血混和乌司他丁。对照组常规进行瓣膜置换手术。分别在麻醉诱导期、转流结束即刻、转流结束后6、12、24h取桡动脉血,应用放射免疫法测定肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)水平;同时记录机械辅助通气时间。结果:两组患者体外循环后上述参数水平开始升高,24h仍高于术前(P<0.01),但肺保护组TNF-α、IL-6、IL-8水平上升幅度在各时间点均低于对照组(P<0.05或P<0.01)。肺保护组机械辅助通气时间显著低于对照组(P<0.01)。结论:持续肺动脉灌注低温含氧血混和乌司他丁能够减轻体外循环术后肺损伤。     

乌司他丁对急性百草枯中毒大鼠肺病理改变的作用研究

目的通过研究乌司他丁（utinastatin,UTI）对急性百草枯（paraquat,PQ）中毒大鼠肺病理学改变的作用研究,探讨乌司他丁对PQ中毒大鼠的肺损伤是否具有保护作用。方法取SD大鼠72只,随机均分为三组,中毒组、乌司他丁组和正常对照组。中毒组及乌司他丁组用百草枯120mg/kg灌胃,一次性染毒;乌司他丁组从染毒后2h开始,腹腔内注射乌司他丁7.5万U/kg,1次/d,至处死前;中毒组及正常对照组用等体积无菌生理盐水腹腔内注射,1次/d,至处死前。分三个不同时间点（6、24、72h）处死大鼠（每组每个时间点8只）,并取肺组织制备标本后分别在光镜及电镜下观察肺组织的病理学改变。结果中毒组大鼠肺的病理学改变为急性弥漫性肺损伤,表现为肺泡腔内出血、渗出,炎性细胞浸润、肺泡隔炎性细胞浸润及纤维组织增生,Ⅰ型和Ⅱ型上皮细胞坏死脱落;乌司他丁组大鼠的病理学改变为局灶性肺泡隔少量炎性细胞浸润,而Ⅰ型上皮细胞完整,Ⅱ型上皮细胞也无明显损伤,未见纤维组织增生。结论从病理学角度观察,乌司他丁对百草枯中毒大鼠的肺损伤具有保护作用。     

乌司他丁对脓毒症急性肺损伤的保护作用研究

目的:观察乌司他丁对脓毒症急性肺损伤的保护作用,并探讨其可能的作用机制。方法:收集2017-04—2018-05期间接受治疗的脓毒症伴发急性肺损伤患者124例,按照患者入院顺序随机分为观察组和对照组,每组62例。对照组常规治疗,观察组在常规治疗基础上加用乌司他丁20万单位/d,静脉滴注。ELISA法检测p65、TNF-α、IL-6表达。结果:治疗前,两组p65、TNF-α和IL-6水平比较,差异无统计学意义(P0.05)。治疗后,观察组p65、TNF-α和IL-6水平分别为(24.36±4.33)μg/L、(31.38±6.06)μg/L和(18.52±3.38)μg/L,显著低于对照组的(38.24±7.25)μg/L、(46.36±7.54)μg/L和(32.16±5.23)μg/L(P0.01)。治疗前,两组PaO_2和PaO_2/FiO_2比较,差异无统计学意义(P0.05)。治疗后,观察组PaO_2和PaO_2/FiO_2分别为(80.23±12.63)mmHg、(387.82±62.33)mmHg,均显著高于对照组的(67.28±10.26)mmHg和(322.18±54.27)mm-Hg,差异有统计学意义(P0.05)。观察组有效率为90.3%(56/62),显著高于对照组的75.8%(47/62)。结论:乌司他丁可以抑制脓毒症急性肺损伤患者炎症反应,改善患者肺功能,临床疗效显著。     

乌司他丁对小儿体外循环术后肺损伤的保护作用

目的探讨乌司他丁（Ulinastatin,UTI）对小儿体外循环（cardiopulmonary bypass,CPB）术后肺损伤的保护作用。方法先天性心脏病择期手术患儿27例被随机分为对照组（C组）和试验组（U组）。C组不给药,U组于麻醉诱导后、CPB开始时和主动脉开放时分别给予乌司他丁总量的1／3（15000万U／kg）。于麻醉诱导后（T1）、CPB结束即刻（L）以及CPB术后1h（T3）、12h（T4）和24h（T5）测动脉血浆中IL-8和中性粒细胞弹性蛋白酶（Neutrophil Elastase,NE）水平。于CPB术后1h、2h及4h测动脉血气,并监测CPB术后肺功能指标肺泡．动脉氧分压差（PA-aO2）、氧合指数（OI）。结果CPB结束即刻和术后1h时间点U组NE水平均显著低于C组对应值（P〈0．05）。CPB术后1h时U组IL-8显著低于C组（P〈0．05）。CPB术后1h U组的OI、PA-aO2显著低于C组（P〈0．05）。结论乌司他丁可通过抑制IL-8和NE的过度释放,对小儿CPB诱发的肺损伤起一定的保护作用。     

乌司他丁对心肺转流术心脏手术患者肺损伤的保护作用

心肺转流术(CPB)后通常会出现一种早期难以解释的肺部并发症"泵肺"(pumplung).在进行冠状动脉(冠脉)旁路移植术(CABG)时,其他器官还会出现问题,这与CPB有关,本研究通过观察乌司他丁对CPB心脏手术患者急性肺损伤(ALI)的呼吸力学和氧代i射的影响,探讨其疗效和安全性.     

乌司他丁对大鼠急性肺损伤保护作用的实验研究

乌司他丁作为一个具有广泛抑制各种细胞因子产生的药物,在急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)方面的治疗作用日益受到重视,本研究拟探讨其保护作用机制,报告如下.     

乌司他丁对急性肺损伤患者的免疫调节作用

目的:评价乌司他丁对急性肺损伤(ALI)患者的免疫调节作用。方法:将符合ALI诊断标准的30例患者随机分成对照组(14例)和治疗组(16例)。对照组给予常规治疗,治疗组在常规治疗的基础上加用乌司他丁,疗程为7 d。两组患者治疗前后进行急性病生理学和慢性健康状况评分系统Ⅱ(APACHEⅡ)评分,计算氧合指数;采用酶联免疫吸附法检测血清肿瘤坏死因子(tumor necrosis factor-α,TNF-α)与白细胞介素-6(interleukin-6,IL-6)、IL-8、IL-10水平;采用流式细胞术检测外周血T淋巴细胞亚群百分比(CD3+、CD4+、CD8+);检测免疫球蛋白IgA、IgG、IgE、IgM。统计患者住重症监护病房(ICU)时间及病死率。结果:与对照组比较,治疗组治疗后APACHEⅡ评分下降更明显,氧合指数增加更明显;与治疗前相比,治疗组治疗后CD3+表达明显上升,CD8+下降;治疗组血清TNF-α、IL-6、IL-8水平较对照组显著下降,IL-10水平升高;治疗组患者住ICU时间减少,差异有统计学意义(P<0.05)。两组患者的免疫球蛋白IgA、IgG、IgE、IgM水平及病死率差异无统计学意义(P>0.05)。结论:乌司他丁可在一定程度上改善ALI患者的免疫机能,尤其能增强细胞免疫。     

乌司他丁在食道癌根治术中肺保护作用的研究

目的探讨乌司他丁对食道癌根治术所致肺损伤的保护作用。方法 40例限期行食道癌根治术患者,随机分为乌司他丁组(U组,n=20)和对照组(C组,n=20)。于手术开始前U组按1万U/kg静脉给予乌司他丁,C组给予等容量的生理盐水。于单肺通气开始时(T0)、单肺通气1h(T1)、双肺通气15min(T2)、术后24h(T3)各监测时间点抽取静脉血5ml,并于T0、T1、T2时间点收集支气管肺泡灌洗液(BALF)3ml。用酶联免疫吸附法(ELISA)法测定血浆中TNF-α、IL-6、IL-8、IL-10及BALF中IL-8的浓度。结果血浆中,两组患者T1、T2、T3时点的TNF-α、IL-6、IL-10及T2、T3时点的IL-8浓度均较T0明显升高(P<0.05);乌司他丁组TNF-α、IL-6、IL-8增高幅度较C组小,而IL-10增高幅度大于C组,差异均T1有统计学意义(P<0.05)。BALF中,C组T1、T2时间点、U组T2时间点IL-8浓度较T0均升高(P<0.05)。U组患者在T1、T2时间点IL-8浓度较C组明显降低(P<0.05)。结论乌司他丁可抑制血浆中TNF-α、IL-6、IL-8及BALF中IL-8浓度,并增加血浆中IL-10的浓度,从而减轻食道癌根治术引发的肺损伤。     

乌司他丁丹参注射液联合治疗创伤后急性肺损伤的临床研究

目的 探讨乌司他丁、丹参注射液联合治疗对创伤后急性肺损伤(ALI)的效果及机制.方法 将60例急诊胸腹部创伤患者随机分为治疗组和对照组,每组30例,两组常规治疗相同.治疗组加用乌司他丁600 kU/d、丹参注射液30 mL/d静脉注射.观察两组患者治疗前后血气分析、住院时间、住ICU时间、急性呼吸窘迫综合征(ARDS)发生率和病死率,并测定血浆肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平.结果 治疗组住院时间、住ICU时间、ARDS发生率和病死率均显著优于对照组(P<0.01);治疗组呼吸频率、动脉血氧分压、氧合指数改善程度均显著优于对照组(P<0.01);治疗组TNF-α、IL-6水平均显著低于对照组(P<0.01).结论 乌司他丁、丹参注射液联合治疗能显著改善创伤后急性肺损伤预后,缩短治疗时间,具有积极推广价值.     

Reduction in alveolar macrophages attenuates acute ventilator induced lung injury in rats

Objective Alveolar macrophages are the sentinel cell for activation of the inflammatory cascade when the lung is exposed to noxious stimuli. We investigated the role of macrophages in mechanical lung injury by comparing the effect of high-volume mechanical ventilation with or without prior depletion of macrophages. Design and setting Randomized sham-controlled animal study in anesthetized rats. Methods Lung injury was induced by 15 min of mechanical ventilation (intermittent positive pressure ventilation) using high peak pressures and zero end-expiratory pressure. The mean tidal volume was 40 ± 0.7 ml/kg. One group of animals was killed immediately after this period of volutrauma (HV), while in a second group normoventilation was continued for 2 h at a tidal volume less than 10 ml/kg (HV-LV). One-half of the animals were depleted of alveolar macrophages by pretreatment with intratracheal liposomal clodronate (CL₂MDP). Measurements Arterial blood gas, blood pressure. After kill: lung static pressure volume curves, bronchoalveolar fluid concentration for protein, macrophage inflammatory protein 2, tumor necrosis factor α, and wet/dry lung weight ratio (W/D). Results During HV and HV+LV oxygenation, lung compliance, and alveolar stability were better preserved in animals pretreated with CL₂MDP. In both groups W/D ratio was significantly greater in ventilated than in nonventilated animals (4.5 ± 0.6), but the increase in W/D was significantly less in CL₂MDP treated HV and HV-LV groups (6.1 ± 0.4, 6.6 ± 0.6) than in the similarly ventilated nontreated groups (8.7 ± 0.2 and 9.2 ± 0.5). Conclusions Alveolar macrophages participate in the early phase of ventilator-induced lung injury. This research was performed at the University of South Alabama, Mobile, AL.     

Ulinastatin for acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis

AIM: To investigate the efficacy and safety of ulinastatin for patients with acute lung injury (ALI) and those with acute respiratory distress syndrome (ARDS).METHODS: A systematic review of randomized controlled trials (RCTs) of ulinastatin for ALI/ARDS was conducted. Oxygenation index, mortality rate [intensive care unit (ICU) mortality rate, 28-d mortality rate] and length of ICU stay were compared between ulinastatin group and conventional therapy group. Meta-analysis was performed by using Rev Man 5.1.RESULTS: Twenty-nine RCTs with 1726 participants were totally included, the basic conditions of which were similar. No studies discussed adverse effect. Oxygenation index was reported in twenty-six studies (1552 patients). Ulinastatin had a significant effect in improving oxygenation [standard mean difference (SMD) = 1.85, 95%CI: 1.42-2.29, P < 0.00001, I² = 92%]. ICU mortality and 28-d mortality were respectively reported in eighteen studies (987 patients) and three studies (196 patients). We found that ulinastatin significantly decreased the ICU mortality [I² = 0%, RR = 0.48, 95%CI: 0.38-0.59, number needed to treat (NNT) = 5.06, P < 0.00001], while the 28-d mortality was not significantly affected (I² = 0%, RR = 0.78, 95%CI: 0.51-1.19, NNT = 12.66, P = 0.24). The length of ICU stay (six studies, 364 patients) in the ulinastatin group was significantly lower than that in the control group (SMD = -0.97, 95%CI: -1.20--0.75, P < 0.00001, I² = 86%).CONCLUSION: Ulinastatin seems to be effective for ALI and ARDS though most trials included were of poor quality and no information on safety was provided.     

呼吸机致大鼠急性肺损伤的实验研究

目的探讨不同潮气量机械通气在大鼠急性肺损伤发生中的作用。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。分别在肉眼、光镜和电镜下观察各组大鼠肺组织病理学改变,测定动脉血气和BALF中性粒细胞计数(PMN)、蛋白含量和髓过氧化物酶(MPO)活性。结果小潮气量组肺组织在肉眼、光镜和电镜下观察与对照组比较差异无显著性;常规潮气量和大潮气量组肺组织在光镜和电镜下可观察到具有不同程度损伤改变,其BALF中PMN、MPO活性和蛋白含量均明显高于对照组和小潮气量组,而动脉血氧分压(PaO_2)明显低于对照组和小潮气量组(P＜0．01,P＜0．05);大潮气量组BALF中MPO活性和蛋白含量与常规潮气量组比较差异也有显著性(P＜0．01);小潮气量组各项指标与对照组比较差异均无统计学意义(P＞0．05)。结论小潮气量通气对正常肺组织无明显影响,但没有任何肺保护措施的常规潮气量通气对正常肺组织具有一定损伤作用,其损伤作用与中性粒细胞在肺内募集和活化有密切关系。     

Blood acidification enhances carbon dioxide removal of membrane lung: an experimental study

Purpose  Extracorporeal CO₂ removal is an effective procedure to allow a protective ventilatory strategy in ARDS patients, but it is technically challenging due to the high blood flow required. Increasing the CO₂ transfer through the membrane lung (ML) may lower the demand of extracorporeal blood flow and consequently allow for a wider clinical application of this technique. Since only the dissolved CO₂ (5% of the total CO₂ content) is easily removed by the ML, we tested whether acidifying the blood entering the ML to convert bicarbonate ions towards dissolved CO₂ could enhance the CO₂ transfer though the ML. Methods  Six pigs were connected to an extracorporeal circuit comprising a ML. The extracorporeal blood flow was 500 ml/min, while the gas flow was 10 l/min. A 15-min continuous infusion of 0.5 N lactic acid was added to the extracorporeal blood flow before the ML at a rate of 1, 2 and 5 mEq/min. Between steps we waited for a reequilibration time of at least 30 min. Results  Acid infusion at 0, 1, 2 and 5 mEq/min increased pCO₂ (56.19 ± 7.92, 68.24 ± 11.73, 84.28 ± 11.17 and 136.66 ± 18.46 mmHg, respectively) and decreased pH (7.39 ± 0.05, 7.30 ± 0.05, 7.20 ± 0.05 and 6.91 ± 0.05, respectively). ML CO₂ removal increased 11, 23 and 70% during acid infusion at 1, 2 and 5 mEq/min, respectively. Conclusions  Blood acidification at the inlet of a ML with infusion of 1, 2 and 5 mEq/min of lactic acid can increase the CO₂ removal capacity of the ML up to 70%. The procedure described here is part of a blood processing technique for which patents are pending, International Patent Application: PCT/EP 2008/003661, 7 May 2008 and Italy: MI2007A000913, 7 May 2007.     

乌司他丁联合无创正压通气治疗48例急性肺损伤患者血气指标分析及临床疗效比较

目的研究乌司他丁联合无创正压通气(NIPPV)治疗急性肺损伤(ALI)患者血气指标及临床疗效。方法选择ALI患者作为研究对象,随机分为观察组(给予乌司他丁联合NIPPV治疗)和对照组(乌司他丁联合气管插管、呼吸机辅助呼吸治疗),观察两组血气和药代动力学指标。结果观察组动脉血氧分压(PaO2)、氧和指数(PaO2/FiO2)、pH值、乌司他丁浓度峰值均明显高于对照组,动脉血二氧化碳分压(PaCO2)达到峰值的时间和半衰期明显低于对照组。结论乌司他丁联合NIPPV治疗ALI患者能够有效的改善血气指标、保证血药浓度,具有积极的临床价值。     

胆碱能抗炎通路对大鼠呼吸机相关性肺损伤的影响

目的 研究胆碱能抗炎通路对呼吸机相关性肺损伤(VILI)的影响.方法 36只SD大鼠按随机数字表法分为自主呼吸对照组、机械通气组、烟碱治疗组,每组12只.采用大潮气量(VT)通气制作大鼠VILI模型.于机械通气前10 min腹腔注射烟碱生理盐水2 mg/kg,其余两组注射等量生理盐水.各组大鼠均行血流动力学和动脉血气监测;通气2 h处死大鼠取肺组织,测定肺湿/干重(W/D)比值和髓过氧化物酶(MPO)活性,采用酶联免疫吸附法(ELISA)测定支气管肺泡灌洗液(BALF)中白细胞介素-8(IL-8)含量及肺组织匀浆细胞间黏附分子-1(ICAM-1)含量;苏木素-伊红(HE)染色观察肺组织病理改变,按修改后弥漫性肺泡损伤评分系统(DAD)进行评分.结果 机械通气期间,机械通气组和烟碱治疗组动脉血pH值呈升高趋势,动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、平均动脉压(MAP)均呈下降趋势.机械通气2 h,烟碱治疗组PaO2(mm Hg,1 mm Hg=0.133 kPa)显著高于机械通气组(85±4比76±3,P<0.05).机械通气组肺W/D比值和MPO活性显著高于对照组[W/D比值:5.66±0.33比4.53±0.21,P<0.01;MPO(U/g):1.73±0.50比0.89±0.17,P<0.05];烟碱治疗组肺W/D比值(5.02±0.37)和MPO活性(1.11±0.33)显著低于机械通气组(均P<0.05).与对照组比较,机械通气组和烟碱治疗组DAD评分(分:10.40±1.85、7.90±1.67比1.60±1.20)、IL-8(ng/L:1 625.3±271.7、965.5±310.5比428.5±120.6)及ICAM-1(μg/L:589.4±87.5、452.5±89.3比247.5±73.7)显著升高(均P<0.01),但烟碱治疗组各指标明显低于机械通气组(P<0.05或P<0.01).结论 胆碱能抗炎通路可抑制VILI大鼠肺组织中IL-8、ICAM-1的表达,减少中性粒细胞在肺内的黏附与渗出,从而减轻肺损伤.     

静脉注射内毒素致大鼠急性肺损伤模型的病理生理学指标评价

目的 观察静脉注射内毒素所致大鼠急性肺损伤（ALI）模型的病理生理学指标，全面评价该模型。方法 将33只Wistar大鼠随机分为实验组和对照组，对照组于静脉注射生理盐水后2h处死动物，实验组静脉注射革兰阴性菌脂多糖后分别于2、4和6h后处死，比较各组死亡率、呼吸频率、肺脏病理、血气指标、肺顺应性、右肺湿重／体重比值、血清和支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）水平。结果实验组6h动脉血氧分压（PaO）跌至69．18mmHg（1mmHg=0．133kPa）；肉眼肺脏可见明显淤血、出血点和水肿；光镜下肺泡正常结构消失，间质水肿增宽，大量炎性细胞浸润，毛细血管明显扩张、充血，白细胞附壁；肺顺应性跌至正常值的47％，右肺湿重／体重比值相当于正常值的137％；血清、BALF中TNF-α水平急剧升高。结论以肺部特征性病理改变和PaO2下降大于30％（与基线值相比）作为判定大鼠ALI模型是否成功的主要指标；以肺顺应性、湿重／体重比值作为辅助指标，可能更适合于大鼠ALI模型。     

机械能：评估呼吸机相关肺损伤的新思路

机械能是指呼吸机为实现肺通气而传递给呼吸系统的能量，能量大小可以通过P-V环的曲线下面积得到，也可以将能量表示为包含呼吸机参数和肺部特性的函数。近年来，有研究者认为机械能或许是一个从总体上评估呼吸机相关肺损伤的良好指标，进而用于指导最佳的机械通气策略。     

Positive end-expiratory pressure alters the severity and spatial heterogeneity of ventilator-induced lung injury: An argument for cyclical airway collapse

Purpose

Ventilator-induced lung injury (VILI) is a recognized complication of mechanical ventilation. Although the specific mechanism by which mechanical ventilation causes lung injury remains an active area of study, both alveolar overdistension and cyclical airway collapse and recruitment have been suggested as contributing causes. We hypothesized that mechanical ventilation in the absence of positive end-expiratory pressure (PEEP) causes VILI to be more severe and regionally variable as compared with PEEP = 8 cm H₂O.

Materials and Methods

To test this hypothesis, anesthetized, supine rabbits were mechanically ventilated with an end-inspiratory pressure of 28 cm H₂O and either 0 or 8 cm H₂O PEEP for 4 hours. Regional lung injury was determined by histologic scoring.

Results

In the absence of PEEP, lung injury was regionally variable and greatest in the dorsal-caudal lung. This regional injury heterogeneity was abolished by the addition of PEEP = 8 cm H₂O.

Conclusions

These results suggest that VILI is regionally heterogeneous and spatially correlates with regions in which cyclical airway collapse and recruitment is most likely to occur.