Effects of partial liquid ventilation on lipopolysaccharide-induced inflammatory responses in rats

To determine whether partial liquid ventilation (PLV) modified lung inflammatory response, we analyzed blood cytokine levels and cytokine mRNA expression in the lungs, using a rat model of endotoxemia. Thirty-six rats were allocated into one of four groups. The first group received conventional gas ventilation (CV group), the second group received 10 ml/kg perflubron intratracheally in combination with mechanical gas ventilation (PLV group), the third group received 20 mg/kg Escherichia coli lipopolyssacharide (LPS) intravenously in combination with mechanical gas ventilation (LPS group), and the fourth group received PLV and LPS (PLV + LPS group). Blood levels of TNF-alpha, IL-1beta, IL-6, IL-10, INF-gamma and IL-1 receptor antagonist were significantly increased in LPS and PLV + LPS groups. mRNA expression of pro- and anti-inflammatory cytokines in the lung tissue was also significantly increased in these groups. mRNA expression of IL-6 in PLV + LPS group was significantly increased in comparison with LPS group. Other cytokine mRNA expression including IL-10 and IL-1beta was also potentiated in PLV + LPS group, however this was not significant. Our results suggest that PLV does not protect the lungs against inflammation in systemic endotoxemia in rats.     

Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model.

We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus. 55 Sprague-Dawley rats were randomized to either intravenous saline or lipopolysaccharide (LPS). After 50 min of spontaneous respiration, the lungs were excised and randomized to 2 h of ventilation with one of four strategies: (a) control (C), tidal volume (Vt) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), Vt = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), Vt = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), Vt = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNFalpha, IL-1beta, IL-6, IL-10, MIP-2, and IFNgamma were measured by ELISA. Zero PEEP in combination with high volume ventilation (HVZP) had a synergistic effect on cytokine levels (e.g., 56-fold increase of TNFalpha versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three-fold increase in TNFalpha, whereas MVZP produced a six-fold increase in lavage TNFalpha. Northern blot analysis revealed a similar pattern (C, MVHP < MVZP < HVZP) for induction of c-fos mRNA. These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung, and thus may play a role in initiating or propagating a local, and possibly systemic inflammatory response.     

Effects of positive end-expiratory pressure in an experimental model of acute myocardial infarct in wistar rats

ABSTRACT: Our purpose in this study was to access the pulmonary effects of mechanical ventilation with positive end-expiratory pressure (PEEP; 10 cmH2O) or without PEEP (zero PEEP-ZEEP) in a rat model of acute myocardial infarction that resulted in hypotension but not in pulmonary congestion. METHODS: Wistar rats were anesthetized (1.5% isoflurane) and myocardial infarct was induced by ligature of the anterior interventricular coronary artery. Rats with myocardial infarct were compared with sham-operated (Sham) and closed thorax groups. RESULTS AND CONCLUSION: There was a significant decrease in MAP in the acute myocardial infarct group (92.5 +/- 4.2 mmHg) when compared with closed chest group (113.0 +/- 4.4 mmHg). There was no significant difference between acute myocardial infarct and Sham groups in PEEP or ZEEP. Mechanical ventilation for 120 min resulted in a significant increase in respiratory system elastance in the groups ventilated with ZEEP (2.59 +/- 0.17 and 2.32 +/- 0.17 cmH2O.mL, Sham and acute myocardial infarct groups, respectively). This effect of mechanical ventilation was not observed in the presence of PEEP in both groups. There was no significant increase in the amount of perivascular pulmonary edema measured in all groups studied. Mean airspace linear intercept and lung tissue distortion index also did not show statistically significant difference between Sham and acute myocardial infarct groups. We conclude that in this experimental model of acute myocardial infarct (12.4 +/- 4.1% area of necrotic tissue and 26.4 +/- 4.0% area of ischemic tissue), there was a protective pulmonary effect of PEEP.     

Effects of cyclic opening and closing at low- and high-volume ventilation on bronchoalveolar lavage cytokines

OBJECTIVE: To examine the mechanisms of ventilator-induced lung injury at low and high lung volumes. DESIGN: Prospective, randomized, laboratory study. SETTING: University research laboratory. SUBJECTS: Eighty-eight adult male Sprague-Dawley rats. INTERVENTIONS: Mechanical ventilation using low and high lung volumes. MEASUREMENTS AND MAIN RESULTS: An ex vivo rat lung model was used. In study I (ventilation at low lung volumes), rat lungs (n = 40) were randomly assigned to various modes of ventilation: a) opening and closing with positive end-expiratory pressure (PEEP; control): tidal volume 7 mL/kg and PEEP 5 cm H2O; b) opening and closing from zero end-expiratory pressure (ZEEP): tidal volume 7 mL/kg and PEEP 0; or c) atelectasis. Peak inspiratory pressure was monitored at the beginning and end of 3 hrs of ventilation. At the end of 3 hrs of ventilation, the lungs were lavaged, and the concentrations of tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6 cytokines were measured in the lavage. In study II (ventilation at high volumes), rat lungs (n = 45) were randomly assigned to a) cyclic lung stretch: pressure-controlled ventilation, peak inspiratory pressure 50 cm H2O, and PEEP 8 cm H2O; b) continuous positive airway pressure at 50 cm H2O (CPAP50); or c) CPAP at the mean airway pressure of the cyclic stretch group (CPAP 31 cm H2O). Bronchoalveolar lavage cytokine concentrations (tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6) were measured at the end of 3 hrs of ventilation. In the low volume study, there was no difference in bronchoalveolar lavage cytokine concentrations between the PEEP group and the atelectatic group. All cytokines were significantly higher in the ZEEP group compared with the atelectasis group. Macrophage inflammatory protein-2 was significantly higher in the ZEEP group compared with the PEEP group. Lung compliance, as reflected by change in peak inspiratory pressure, was also significantly worse in the ZEEP compared with the PEEP group. In the high-volume study, tumor necrosis factor-alpha and interleukin-6 were significantly higher in the cyclic stretch group compared with the CPAP 31 group. There was no significant difference between the cytokine concentrations in the cyclic stretch group compared with the CPAP 50 group. CONCLUSION: We conclude that at low lung volumes, cyclic opening and closing from ZEEP leads to greater increases in bronchoalveolar lavage cytokines than atelectasis. With high-volume ventilation, over time, the degree of overdistension is more associated with increases in bronchoalveolar lavage cytokines than cyclic opening and closing alone.     

Effects of protective and conventional mechanical ventilation on pulmonary function and systemic cytokine release after cardiopulmonary bypass

Objective To evaluate the effects of protective and conventional ventilation with or without positive end-expiratory pressure (PEEP), on systemic tumor necrosis factor-, interleukin-6 levels and pulmonary function during open heart surgery.Design Prospective, randomized clinical study.Setting Single university hospital.Patients and participants Forty-four patients undergoing elective coronary artery bypass grafting surgery with cardiopulmonary bypass.Interventions Patients ventilated with (1) protective tidal volumes (6 ml/kg, respiratory rate: 15 breaths/min, PEEP 5 cmH₂O, n=15) group PV; (2) conventional tidal volumes (10 ml/kg, respiratory rate: 9 breaths/min, PEEP 5 cmH₂O, n=14) group CV+PEEP and (3) conventional tidal volumes (10 ml/kg, respiratory rate: 9 breaths/min, n=15) without PEEP, group CV+ZEEP. Various pulmonary parameters, systemic TNF- and IL-6 levels were determined throughout the study.Measurements and results There were no differences among the groups regarding the systemic TNF- and IL-6 levels. The plateau airway pressures of group PV were lower than those of groups CV+PEEP (p=0.02) and CV+ZEEP (p=0.001) after cardiopulmonary bypass. The shunt fraction of group PV was significantly lower than that of group CV+ZEEP 24 h after surgery (p<0.05). Oxygenation and the alveolar-arterial oxygen difference were better in both PEEP groups than in group CV+ZEEP 24 h after the operation.Conclusions We could not find any evidence that protective mechanical ventilation prevents some of the adverse effects of cardiopulmonary bypass on the lung, nor systemic cytokine levels, postoperative pulmonary function or length of hospitalization.This research is partially supported by Fresenius—Kabi and Aventis Pharma.     

Effects of body temperature on ventilator-induced lung injury

PURPOSE: To evaluate the effects of body temperature on ventilator-induced lung injury. MATERIAL AND METHODS: Thirty-four male Sprague-Dawley rats were randomized into 6 groups based on their body temperature (normothermia, 37 +/- 1 degrees C; hypothermia, 31 +/- 1 degrees C; hyperthermia, 41 +/- 1 degrees C). Ventilator-induced lung injury was achieved by ventilating for 1 hour with pressure-controlled ventilation mode set at peak inspiratory pressure (PIP) of 30 cmH2O (high pressure, or HP) and positive end-expiratory pressure (PEEP) of 0 cmH2O. In control subjects, PIP was set at 14 cmH2O (low pressure, or LP) and PEEP set at 0 cmH2O. Systemic chemokine and cytokine (tumor necrosis factor alpha , interleukin 1 beta , interleukin 6, and monocyte chemoattractant protein 1) levels were measured. The lungs were assessed for histological changes. RESULTS: Serum chemokines and cytokines were significantly elevated in the hyperthermia HP group compared with all 3 groups, LP (control), normothermia HP, and hypothermia HP. Oxygenation was better but not statistically significant in hypothermia HP compared with other HP groups. Cumulative mean histology scores were higher in hyperthermia HP and normothermia HP groups compared with control and normothermia HP groups. CONCLUSIONS: Concomitant hyperthermia increased systemic inflammatory response during HP ventilation. Although hypothermia decreased local inflammation in the lung, it did not completely attenuate systemic inflammatory response associated with HP ventilation.     

Low tidal volume ventilation induces proinflammatory and profibrogenic response in lungs of rats

Objective We examined whether mechanical ventilation with low tidal volume induces polymorphonuclear infiltration and proinflammatory and profibrogenic responses in rat lungs compared dependent and nondependent lung region to expression of interleukin-1 (IL-1) and -1 procollagen III (PC III) mRNA.Design An experimental, randomized and controlled protocol with previously normal rats.Interventions Three groups of ten animals were studied. Two groups were ventilated (FIO₂=0.3) in supine position for 1 h without positive end expiratory pressure, one group with a low tidal volume (6 ml/kg), and the other with a high tidal volume (24 ml/kg). In the third group animals were kept in spontaneous ventilation for 1 h.Measurements and results After ventilation the right lung was used to quantify polymorphonuclear infiltration. The left lung was divided into dependent and nondependent regions, and expression of IL-1 and PC III mRNA was quantified by northern blot analysis. The group ventilated with low tidal volume had greater polymorphonuclear infiltration IL-1 and PC III mRNA expression than the nonventilated group. Similar results were observed with high tidal volumes. There was no difference between low and high tidal volume ventilation. Expression levels of IL-1 and PC III mRNA were higher in the nondependent region of ventilated groups and equal in the nonventilated group.Conclusions Even a low tidal volume mode of mechanical ventilation induces proinflammatory and profibrogenic response, with a nondependent predominance for IL-1 and PC III mRNA expression in supine, ventilated, previously normal rats.     

机械通气对急性肺损伤大鼠细胞凋亡的影响

目的 研究不同潮气量及不同呼气末正压(PEEP)水平对急性肺损伤(AU)大鼠支气管和肺组织细胞凋亡的影响,并初步探讨细胞凋亡在呼吸机相关性肺损伤(VILI)中的作用机制.方法 选用40只SD大鼠,制作ALI模型,随机(随机数字法)分为:(1)小潮气量组(LV组),潮气量8 mL/kg,不加PEEP;(2)大潮气量组,潮气量30 mL./kg,不加PEEP;(3)小潮气量+ 2PEEP组(LV2P组),潮气量8 mL/kg,同时给PEEP 2 cmH2O(1 crnH2O =0.098 kPa);(4)小潮气量+5PEEP组(LV5P组),潮气量8 mL/kg,同时给PEEP 5 cmH2O;(5)小潮气量+8PEEP组(LV8P组),潮气量8 mL/kg,同时给PEEP 8 cmH2O.通气2h后处死动物,留取肺标本.用脱氧核糖核苷酸末端转移酶介导的末端标记法(TUNEL)分析肺组织中的细胞凋亡情况,用免疫组化法检测肺组织中caspase-3蛋白的表达及分布.结果 大潮气量组支气管和肺组织细胞凋亡的明显增加(P＜0.01),caspase-3蛋白酶表达最强.采用PEEP后,支气管和肺组织细胞凋亡减少,capase-3蛋白酶表达弱阳性,以LV5P组最为显著(P＜0.01).结论 小潮气量对肺组织有保护作用,采用PEEP后保护作用更加明显,细胞凋亡在VILI的发生中有重要作用.     

High-molecular-weight hyaluronan – a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats

Introduction

Mechanical ventilation with even moderate-sized tidal volumes synergistically increases lung injury in sepsis and has been associated with proinflammatory low-molecular-weight hyaluronan production. High-molecular-weight hyaluronan (HMW HA), in contrast, has been found to be anti-inflammatory. We hypothesized that HMW HA would inhibit lung injury associated with sepsis and mechanical ventilation.

Methods

Sprague–Dawley rats were randomly divided into four groups: nonventilated control rats; mechanical ventilation plus lipopolysaccharide (LPS) infusion as a model of sepsis; mechanical ventilation plus LPS with HMW HA (1,600 kDa) pretreatment; and mechanical ventilation plus LPS with low-molecular-weight hyaluronan (35 kDa) pretreatment. Rats were mechanically ventilated with low (7 ml/kg) tidal volumes. LPS (1 or 3 mg/kg) or normal saline was infused 1 hour prior to mechanical ventilation. Animals received HMW HA or low-molecular-weight hyaluronan via the intraperitoneal route 18 hours prior to the study or received HMW HA (0.025%, 0.05% or 0.1%) intravenously 1 hour after injection of LPS. After 4 hours of ventilation, animals were sacrificed and the lung neutrophil and monocyte infiltration, the cytokine production, and the lung pathology score were measured.

Results

LPS induced lung neutrophil infiltration, macrophage inflammatory protein-2 and TNFα mRNA and protein, which were decreased in the presence of both 1,600 kDa and 35 kDa hyaluronan pretreatment. Only 1,600 kDa hyaluronan completely blocked both monocyte and neutrophil infiltration and decreased the lung injury. When infused intravenously 1 hour after LPS, 1,600 kDa hyaluronan inhibited lung neutrophil infiltration, macrophage inflammatory protein-2 mRNA expression and lung injury in a dose-dependent manner. The beneficial effects of hyaluronan were partially dependent on the positive charge of the compound.

Conclusions

HMW HA may prove to be an effective treatment strategy for sepsis-induced lung injury with mechanical ventilation.     

俯卧位通气联合呼气末正压治疗急性呼吸窘迫综合征家猪的疗效研究

目的 探讨俯卧位通气联合呼气末正压(PEEP)治疗急性呼吸窘迫综合征(ARDS)的疗效及其机制.方法 12头家猪静脉注射油酸建立ARDS模型,分为仰卧位组和俯卧位组,均给予0(ZEEP)、10(PEEP10)、20 cm H2O(PEEP20,1 cm H2O=0.098 kPa)PEEP的机械通气15 min,监测家猪血流动力学、肺气体交换和呼吸力学指标;处死动物观察肺组织病理学变化.结果 俯卧位组ZEEP、PEEP10时氧合指数(PaO2/FiO2)明显优于仰卧位组[ZEEP:(234.00±72.55)mm Hg比(106.58±34.93)mm Hg,PEEP10:(342.97±60.15) mm Hg比(246.80±83.69)mm Hg,1 mm Hg=0.133 kPa,P均<0.05];PEEP20时两组PaO2/FiO2差异无统计学意义(P>0.05).PEEP10时两组肺复张容积(RV)差异无统计学意义(P>0.05);但PEEP20时俯卧位组RV显著高于仰卧位组[(378.55±101.80)ml比(302.95±34.31)ml,P<0.05].两组间心率(HR)、平均动脉压(MAP)、心排血指数(CI)、呼吸系统顺应性(Cst)及动脉血二氧化碳分压(PaCO2)差异均无统计学意义(P均>0.05);仰卧位组背侧肺组织的肺损伤总评分明显高于俯卧位组[(12.00±1.69)分比(6.03±1.56)分,P<0.05].结论 俯卧位通气联合合适的PEEP可改善ARDS家猪氧合,并且不影响血流动力学和呼吸力学,肺组织损伤的重新分布可能是其机制之一.     

白细胞介素-10对急性肺损伤炎症/抗炎介质表达的影响

目的探讨白细胞介素-10(IL—10)对急性肺损伤(ALI)大鼠炎症介质／抗炎介质表达的影响。方法向气道内滴注内毒素(LPS，10mg／kg)建立大鼠ALI模型。54只雄性SD大鼠随机分为对照组、LPS损伤组、LPS加IL-10组，每组18只，各组又分为2、6和24h3个亚组，每个亚组各6只。按各时间点观察大鼠动脉血氧分压(PaO2)、支气管肺泡灌洗液(BALF)中细胞总数及分类计数、肺系数、BALF总蛋白水平及肺病理，同时用逆转录-聚合酶链反应(RT—PCR)方法检测肺组织中炎症介质／抗炎介质的表达。结果①LPS损伤组大鼠PaO2呈进行性降低；肺系数、BALF总蛋白水平及BALF中细胞总数均明显增加，分类以中性粒细胞为主；肺病理示肺内中性粒细胞大量浸润，伴出血、透明膜形成。LPS加IL-10组的各项指标均较LPS损伤组减轻。②LPS损伤组肺组织肿瘤坏死因子-α(TNF—α)mRNA表达于2h达高峰，随后迅速下降；白细胞介素-1β(IL—1β)mRNA表达于2h显著升高，6h达高峰，随后迅速下降；IL-1受体拮抗剂(IL—1ra)mRNA表达6h开始升高，且为峰值。24h仍高于对照组。LPS加IL-10组肺组织TNF—αmRNA、IL-1βmRNA表达受抑，而IL—1ra mRNA表达不受影响。结论①ALI早期TNF—αmRNA、IL-1βmRNA表达明显增加，而IL—1ra mRNA表达滞后，提示在无外来干预情况下，ALI早期存在炎症介质／抗炎介质的失衡。②IL-10可明显抑制炎症介质表达，不影响抗炎介质表达，有利于重建炎症介质／抗炎介质平衡，减轻LPS所致ALI。     

评分法选择PEEP对ARDS病人的临床价值

目的：研究评分法选择PEEP对ARDS病人的临床价值。方法：对1999年～2004年88例ARDS病人随机使用两种方法选择PEEP进行机械通气。其中评分组（实验组）51例，根据评分法四项指标得分数总和，如评分大于等于6分则PEEP用20-25cmHO；3～5分则PEEP用12～20cmH2O；评分小于等于2分则PEEP用5～12cmH2O；传统方法组（对照组）37例，PEEP均使用5～12cmH2O。分别检测两组病例通气开始时、通气后24h时的血气分析，计算两组病例入ICU30d时病死率，观察其并发症发生情况。结果：实验组较对照组痛死率明显下降，具有极显著差异，P〈0．01；且实验组中采用低PEEP小组的病死率亦较对照组低，具有显著差异，P〈0．05。实验组与对照组在通气24h时都能较通气开始时改善病人的血气情况，且实验组较对照组PaO2升高更明显，具有极显著差异，P〈0．001，而pH、PaCO2在两组无显著差异，P〉0．05。两组均未发生气压伤，实验组较对照组并发MOF的发生率低，具有显著差异，P〈0．05；血压明显下降的发生率高，具有显著差异，P〈0．05，但能纠正。结论：采用评分法选择PEEP较传统方法有更高的临床价值，可明显降低削RDS病人痛死率，改善病人的氧合情况，并且并发症较少或可控制。     

Respiratory mechanics in brain-damaged patients

Objective To assess respiratory mechanics on the 1st and 5th days of mechanical ventilation in a cohort of brain-damaged patients on positive end-expiratory pressure (PEEP) of 8 cmH₂O or zero PEEP (ZEEP).Design and setting Physiological study with randomized control trial design in a multidisciplinary intensive care unit of a university hospital.Patients and measurements Twenty-one consecutive mechanically ventilated patients with severe brain damage and no acute lung injury were randomly assigned to be ventilated with ZEEP (n = 10) or with 8 cmH₂O of PEEP (n = 11). Respiratory mechanics and arterial blood gases were assessed on days 1 and day 5 of mechanical ventilation.Results In the ZEEP group on day 1 static elastance and minimal resistance were above normal limits (18.9 ± 3.8 cmH₂O/l and 5.6 ± 2.2 cmH₂O/l per second, respectively); on day 5 static elastance and iso-CO₂ minimal resistance values were higher than on day 1 (21.2 ± 4.1 cmH₂O/l; 7.0 ± 1.9 cmH₂O/l per second, respectively). In the PEEP group these parameters did not change significantly. One of the ten patients on ZEEP developed acute lung injury. On day 5 there was a significant decrease in PaO₂/FIO₂ in both groups.Conclusions On day 1 of mechanical ventilation patients with brain damage exhibit abnormal respiratory mechanics. After 5 days of mechanical ventilation on ZEEP static elastance and minimal resistance increased significantly, perhaps reflecting “low lung volume” injury. Both could be prevented by administration of moderate levels of PEEP.This work was supported by the Thorax foundation.This article is discussed in the editorial available at:     

外源性呼气末正压对气道压力的影响

目的探讨外源性呼气末正压（PEEP）对气过压力影响的规律。方法通过模拟肺（静态顺应性为28ml／cmH2O,气道阻力为0．8cmH2O·L－1·S-1）试验,设置不同的PEEP,观察气道压力（修压、平均压、平台压）的变化。结果外源性PEEP从0增加至3cmH2O时,气过压力增幅最大,平均每增加1cmH2OPEEP,气道峰压、平台压增加3．5～4．1cmH2O,当PEEP增加至12cmH2O时,气道峰压和平台压增加了20cmH2O以上。结论外源性PEEP对气造压力的影响,可产生一种“扩大”效应,这种“扩大”效应在低水平的PEEP时尤为显著。在使用人工机械通气时,如需设置外源性PEEP时,必须严密监测气道压力的变化,以防止肺损伤。     

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.     

Low spatial resolution computed tomography underestimates lung overinflation resulting from positive pressure ventilation

OBJECTIVE: In acute lung injury, lung overinflation resulting from mechanical ventilation with positive end-expiratory pressure (PEEP) can be assessed using lung computed tomography. The goal of this study was to compare lung overinflation measured on low and high spatial resolution computed tomography sections. DESIGN: Lung overinflation was measured on thick (10-mm) and thin (1.5-mm) computed tomography sections obtained at zero end-expiratory pressure (ZEEP) and PEEP 10 cm H2O using a software including a color-coding system. SETTING: A 20-bed surgical intensive care unit of a university hospital. PATIENTS: Thirty mechanically ventilated patients with acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overinflated lung volume was measured as the end-expiratory volume of lung regions with computed tomography attenuations <-900 Hounsfield units. Lung overinflation, expressed in percentage of the total lung volume, was significantly underestimated by thick computed tomography sections compared with thin computed tomography sections (0.4 +/- 1.6% vs. 3.0 +/- 4.0% in ZEEP and 1.9 +/- 4% vs. 6.8 +/- 7.3% in PEEP, p < .01). In patients with a diffuse loss of aeration, the overinflated lung volumes of thick and thin computed tomography sections were, respectively, 0.6 +/- 0.8 mL vs. 16 +/- 10 mL in ZEEP (p < .01) and 8 +/- 9 mL vs. 73 +/- 62 mL in PEEP (p < .05). In patients with a focal loss of aeration, this underestimation was more pronounced: 18 +/- 56 mL vs. 127 +/- 140 mL in ZEEP (p < .01) and 85 +/- 161 mL vs. 322 +/- 292 mL in PEEP (p < .01). CONCLUSIONS: In patients with acute lung injury, an accurate computed tomography estimation of lung overinflation resulting from positive pressure mechanical ventilation requires high spatial resolution computed tomography sections, particularly when the lung morphology shows a focal loss of aeration.     

Injurious ventilation induces widespread pulmonary epithelial expression of tumor necrosis factor-alpha and interleukin-6 messenger RNA

OBJECTIVE: We examined the hypothesis that injurious strategies of mechanical ventilation alter the expression and distribution within the lung of tumor necrosis factor-alpha and interleukin-6 that are both duration and ventilation strategy dependent. SUBJECTS: Male Sprague Dawley rats. INTERVENTIONS: Lungs from rats were preserved immediately after death or were randomized to ex vivo ventilation with either a) noninjurious ventilation; b) high end-inspiratory lung volume with positive end-expiratory pressure (PEEP); c) high end-inspiratory lung volume without PEEP; or d) intermediate lung distension without PEEP, for periods ranging from 30 mins to 3 hrs. MEASUREMENT AND MAIN RESULTS: Changes in cytokines were assessed by in situ hybridization, immunocytochemistry, simultaneous in situ hybridization and immunocytochemistry, Northern analysis, and enzyme-linked immunosorbent assay. Whereas minimal expression of tumor necrosis factor-alpha and interleukin-6 mRNA was found in lungs subjected to noninjurious ventilation, the three injurious strategies resulted in a diffuse increase in expression of tumor necrosis factor-alpha and interleukin-6. The principal cells involved were the bronchial, bronchiolar, and alveolar epithelium. The changes in tumor necrosis factor-alpha mRNA and protein expression were dependent on both duration of ventilation and the ventilation strategy used. CONCLUSIONS: The vast pulmonary epithelium is a major contributor to ventilation-induced changes in cytokine production and may play an important role in the pathogenesis of lung injury and systemic sequelae in ventilated subjects.     

肺保护性机械通气和传统机械通气治疗新生儿急性呼吸衰竭临床观察

目的观察传统机械通气和肺保护性机械通气治疗新生儿急性呼吸衰竭的临床情况。方法选择40例急性呼吸衰竭新生儿患儿，随机分为两组，A组用传统机械通气，B组用肺保护性机械通气。A组潮气量（VT）10～12ml／kg，气道峰压（PIP）〈25cmH2O，呼气末正气（PEEP）（5．0±1．5）cmH2O，呼吸频率（RR）60次／min；B组VT为5～8ml／kg，PEEP为（7．6±1．5）cmH2O，RR为40～60次／分。结果转归比较：两组所有病人均治愈。呼吸机参数比较：两组在维持SaO2在90％以上且PaCO2〈8．0kPa的呼吸机各项参数，A组的VT（10．11±1．20）ml／kg、PIP（24．01±2．10）cmH2O、PEEP（7．50±1．50）cmH2O，两组VT、PIP差异有非常显著性（P〈0．01），两组PEEP的差异无显著性（P〉0．05）。血气比较：pH值A组7．35±0．10，B组7．25±0．15；PaCO2为A组（6．90±0．72）kPa，B组（93．0±2.8）kPa；两组pH、PaCO2、SaCO2（％）值比较差异均无显著性（P均〉0．05）。两组并发症比较：A组肺损伤4例，循环系统并发症3例，B组无。结论传统策略和肺保护性策略通气均能治愈新生儿急性呼吸衰竭，但后者并发症较少。在维持PH、PaCO2、PaO2、SaO2基本相同的情况下，肺保护性通气的呼吸机参数VT和PIP较传统通气明显降低。     

Mechanical ventilation alters the immune response in children without lung pathology

OBJECTIVE: This study was undertaken to examine the hypothesis that mechanical ventilation in association with anesthesia would alter the cytokine profile in infants without preexisting lung pathology. DESIGN AND SETTING: Prospective observational study in pediatric intensive care unit in a university hospital. PATIENTS: Twelve infants who were subjected to an uncomplicated diagnostic cardiac catheterization procedure were studied. All subjects were ventilated with a volume control mode, 0.3 FIO(2), 4 cmH(2)O PEEP, and 10 ml/kg tidal volume. Volatile (servoflurane) anesthetics were given. MEASUREMENTS AND RESULTS: Tracheal aspirates and blood samples were obtained before and after 2 h of mechanical ventilation. In tracheal aspirates and in supernatants of stimulated whole-blood cultures cytokine concentrations were measured. In the tracheal aspirates the immune balance was characterized by a proinflammatory response pattern, with a significant increase in TNF-alpha and IL-6 concentrations; concentrations of anti-inflammatory mediators remained very low. The functional capacity of peripheral blood leukocytes to produce INF-gamma, TNF-alpha, and IL-6 in vitro was significantly decreased. This was accompanied by a significant decrease in the killing activity of natural killer cells. CONCLUSIONS: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. In the lungs the immune balance favors a proinflammatory response pattern without detectable concentrations of anti-inflammatory mediators. The Th1 immune response by peripheral blood leukocytes was decreased. The observed change in Th1/Th2 balance in favor of Th2 cytokine activity may be a systemic adaptation to the proinflammatory milieu in the lung.     

Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury

Abstract Objective. To investigate the kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury (ALI). Design. Prospective observational cross-over study. Setting. Intensive care unit of a university hospital. Patients. Twelve mechanically ventilated patients with ALI. Interventions. Mechanical ventilation was transiently changed from a lung protective setting with PEEP of 15 cmH₂O and a V_T of 5 ml/kg predicted body weight to a more conventional ventilatory setting with PEEP of 5 cmH₂O and V_T of 12 ml/kg predicted body weight for a period of 6 h. Measurements and results. We examined the profile of interleukin (IL)-1#, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor in the plasma of all patients, and in the bronchoalveolar lavage (mini-BAL) fluid of six of these patients. Measurements were performed at baseline, 1 h, and 6 h after each change of the ventilatory setting. Switching to conventional mechanical ventilation was associated with a higher PaO₂ (P <0.05) and a marked increase (P <0.05) of measured plasma cytokines in patients with and without mini-BAL with a maximum after 1 h. Similarly, intraalveolar cytokine concentrations increased with conventional mechanical ventilation. While plasma cytokine levels returned to baseline values, intraalveolar cytokine concentrations further increased when lung protective mechanical ventilation was reestablished. Conclusions. In patients with ALI, initiation of low PEEP and high V_T mechanical ventilation is associated with cytokine release into circulation which occurred within 1 h. It is independent from BAL procedures and can be reversed by reinstitution of lung protective mechanical ventilation.