Protective effect of pentoxifylline on volume-induced lung injury in newborn piglets

To evaluate the efficacy of pentoxifylline (PTXF) in the attenuation of lung inflammation during volume-induced lung injury (VILI) in newborn piglets, 17 newborn piglets were mechanically ventilated with a large tidal volume (50 ml/kg) for a period of 8 h. They were randomly assigned to a placebo (PL, n = 9) or a treatment group (PTXF, n = 8) that received PTXF (20 mg/kg as a bolus, followed by a continuous infusion of 5 mg/kg/h). Hemodynamics, lung mechanics and arterial blood gases were measured during the 8 h of study. Serum and tracheoalveolar fluid (TAF) platelet-activating factor (PAF) and thromboxane (TXB(2)) levels were obtained at baseline and at 8 h, while lung tissue myeloperoxidase (MPO) and wet to dry weight were assessed after the completion of the study. In the PL group, a marked increase in TAF PAF and TXB(2) levels was observed only in TAF, suggesting that the inflammatory process was localized within the lungs. A significant decrease in lung tissue MPO activity (p < 0.005) and lung wet to dry weight ratio (p < 0.04) was observed in the PTXF group. There were no differences in hemodynamics, arterial blood gases or lung mechanics measurements between groups. A significant reduction in pulmonary inflammatory response was observed during VILI in the PTXF pretreated animals. These results suggest that PTXF may be effective in modulating lung inflammation associated with mechanical ventilation in neonates.     

Partial liquid ventilation versus conventional mechanical ventilation with high PEEP and moderate tidal volume in acute respiratory failure in piglets

This prospective randomized pilot study aimed to test the hypotheses that partial liquid ventilation combined with a high positive end-expiratory pressure (PEEP) and a moderate tidal volume results in improved gas exchange and lung mechanics without negative hemodynamic influences compared with conventional mechanical ventilation in acute lung injury in piglets. Acute lung injury was induced in 12 piglets weighing 9.0 +/- 2.4 kg by repeated i.v. injections of oleic acid and repeated lung lavages. Thereafter, the animals were randomly assigned either to partial liquid ventilation (n = 6) or conventional mechanical ventilation (n = 6) at a fractional concentration of inspired O(2) of 1.0, a PEEP of 1.2 kPa, a tidal volume < 10 mL/kg body weight (bw), a respiratory rate of 24 breaths/min, and an inspiratory/expiratory ratio of 1:2. Perfluorocarbon liquid 30 mL/kg bw was instilled into the endotracheal tube over 10 min followed by 5 mL/kg bw/h. Continuous monitoring included ECG, mean right atrial, pulmonary artery, pulmonary capillary, and arterial pressures, arterial blood gas, and partial pressure of end-tidal CO(2) measurements. When compared with control animals, partial liquid ventilation resulted in significantly better oxygenation with improved cardiac output and oxygen delivery. Dead space ventilation appeared to be lower during partial liquid ventilation compared with conventional mechanical ventilation. No significant differences were observed in airway pressures, pulmonary compliance, and airway resistance between both groups. The results of this pilot study suggest that partial liquid ventilation combined with high PEEP and moderate tidal volume improves oxygenation, dead space ventilation, cardiac output, and oxygen delivery compared with conventional mechanical ventilation in acute lung injury in piglets but has no significant influence on lung mechanics.     

Lipopolysaccharide exposure modifies high tidal volume ventilation-induced proinflammatory mediator expression in newborn rat lungs

Infection/inflammation and mechanical ventilation have both independently been shown to increase cytokine/chemokine levels in lung tissue and blood samples of premature patients. Little is known about the combined effect of systemic inflammation and mechanical ventilation on cytokine expression in the lung. We tested whether pre-existing inflammation induced by lipopolysaccharide (LPS) exposure would modify cytokine/chemokine response in newborn rat lungs to high tidal volume ventilation (HTVV). Newborn rats were randomly assigned to four groups: groups I and II (saline); groups III and IV: 3 mg/kg LPS. Groups II and IV were 24h later subjected to 3h of ventilation with a tidal volume of 25 mL/kg. HTVV alone increased IL-1beta, IL-6 and the chemokine (C-X-C motif) ligand 2 (CXCL2) mRNA expression. Although the cytokine response to LPS alone had disappeared after 24 h, the combination of LPS pretreatment and HTVV significantly increased the expression of IL-6 and IL-1beta mRNA when compared with HTVV alone. TNF-alpha expression was increased neither by HTVV alone nor in combination with LPS. IL-6 protein content in bronchoalveolar lavage increased due to the combined treatment. Thus, a subtle pre-existing inflammation combined with HTVV amplifies the proinflammatory cytokine/chemokine expression in the newborn rat lung compared with HTVV alone.     

Mechanical ventilation effect on surfactant content, function, and lung compliance in the newborn rat

Studies of ventilator-associated lung injury in adult experimental animal models have documented that high tidal volume (TV) results in lung injury characterized by impaired compliance and dysfunctional surfactant. Yet, there is evidence that, in neonates, ventilation with a higher than physiologic TV leads to improved lung compliance. The purpose of our study was to evaluate how lung compliance and surfactant was altered by high TV ventilation in the neonate. We utilized a new model (mechanically air-ventilated newborn rats, 4-8 d old), and used 40 or 10 mL/kg TV strategies. Age-matched nonventilated animals served as controls. In all animals, dynamic compliance progressively increased after initiation of mechanical ventilation and was significantly greater than basal values after 60 min (p < 0.01). Lung lavage total surfactant with both TV strategies (p < 0.05) and the large aggregate fraction (only in TV = 40 mL/kg; p < 0.01) were significantly increased by 60 min of mechanical ventilation, compared with control animals. Ventilation with 40 mL/kg TV for 60 min adversely affected the lung surfactant surface-tension lowering properties (p < 0.01). After 180 min of ventilation with 40 mL/kg TV, the lung total surfactant content and dynamic compliance values were no longer distinct from the nonventilated animals' values. We conclude that, in the newborn rat, mechanical ventilation with a higher than physiologic TV increases alveolar surfactant content and, over time, alters its biophysical properties, thus promoting an initial but transient improvement in lung compliance.     

Monocyte chemoattractant protein-1 and its receptor CCR-2 in piglet lungs exposed to inhaled nitric oxide and hyperoxia.

Monocyte chemoattractant protein-1 (MCP-1), acting through its C-C chemokine receptor 2 (CCR-2), has important roles in inflammation, angiogenesis, and wound repair. The individual and combined effects of inhaled nitric oxide (NO) and hyperoxia on lung MCP-1 and CCR-2 in relation to lung leukocyte dynamics are unknown. Because MCP-1 gene is up-regulated by oxidants, we hypothesized that inhaled NO with hyperoxia will increase MCP-1 production and CCR-2 expression more than either gas alone. We randomly assigned young piglets to breathe room air (RA), RA+50 ppm NO (RA+NO), O(2), or O(2)+NO for 1 or 5 d before sacrifice. Lungs were lavaged and tissues preserved for hybridization studies, Western blotting, histology, and immunohistochemistry. The results show that lung MCP-1 production and alveolar macrophage count were significantly elevated in the 5-d O(2) and O(2)+NO groups relative to the RA group (p < or = 0.05). In contrast, lung CCR-2 abundance was diminished in the O(2) group (p 相似文献   

电阻抗测量评估不同的通气频率和呼气末正压时局部肺容量变化的研究

目的 机械通气期间气体的不均匀分布,特别是由于肺不张引起的不均匀的通气可引起健康肺泡的过度通气,导致急性肺损伤和慢性肺疾病,因而增加了病死率和发病率.特别是早产儿需要长期应用机械通气的更是处于危险的状态.新的策略主要是持续监护局部通气可解决不均匀充气的问题.方法对6个健康的新生猪(4 d±1 d,1.66±0.31 kg)应用8个电极分布于肺的四个部分(上、下、左、右)进行电阻抗测量(EIM).潮气阻抗和功能残气阻抗随着呼气末正压(PEEP)水平的变化[2、4、6和8 cm H2O(1 cm H2O=0.098 kPa)]和呼吸机频率从0.5到15 Hz的变化进行观察.同时评估总的肺和局部肺的变化.结果从肺的4个部分获得的局部潮气阻抗总和明显反映了与在改变呼吸机频率和PEEP期间由肺体积扫描术测得的潮气量(r2=0.98),PEEP从4 cm H2O降至2 cm H2O,引起总潮气阻抗(TTI)明显增加,同样潮气量(VT)也增加,而呼吸频率从0.5升至15 Hz,引起TTI和VT明显降低.增加频率发现有一个较均匀的气体分布作用,但高的PEEP不会引起更均匀的通气,获得的最小阻抗值代替功能残气量(FRC)显示在6 h的实验期间持续下降.结论 EIM对评估胸腔气体容量显示很好的适应性,这种方法提示作为一种非损伤性的床边的方法持续监护新生儿任何模式下的机械通气中局部肺通气的变化,可获得一定的影响,对临床有一定的参考价值.     

How safe is intermittent positive pressure ventilation in preterm babies ventilated from delivery to newborn intensive care unit?

Objectives: To examine whether clinically determined ventilator settings will produce acceptable arterial blood gas values on arrival, in preterm infants ventilated from delivery to the newborn intensive care unit (NICU). Further, to examine the usefulness of tidal volume and minute ventilation measurements at this time. Design: A prospective observational cohort study in a tertiary level 3 NICU. Patients: Twenty six preterm infants requiring intubation and mechanical ventilation at the point of delivery to the NICU. Setting: Infants who required mechanical ventilation were monitored with a blinded Ventrak 1550 dynamic lung function monitor from the point of delivery to the NICU. A Dräger Babylog 2000 transport ventilator was set up to achieve adequate chest wall movement, and FIO₂ was adjusted to achieve preductal SaO₂ of 90–98%. Dynamic lung function monitoring data were recorded and related to the arterial blood gas taken on arrival. Results: Mean gestation was 28 weeks (range 23–34) and mean birth weight was 1180 g (range 480–4200). A quarter (26% (95% confidence interval (CI) 12% to 48%)) were hypocarbic, with 20% (95% CI 7% to 39%) below 25 mm Hg, and 38% (95% CI 20% to 60%) had hyperoxia. Some (20% (95% CI 7% to 39%)) were both hypocarbic and hyperoxic. Total minute ventilation per kilogram correlated significantly with the inverse of PaCO₂ (p < 0.001). Conclusions: Clinically determining appropriate mechanical ventilation settings from the point of delivery to the NICU is difficult, and inadvertent overventilation may be common. Severe hyperoxia can occur in spite of adjustment of the FIO₂ concentration to achieve an SaO₂ range of 90–98%. Limiting minute ventilation during resuscitation may prevent hypocarbia.     

Dynamics of breathing during partial liquid ventilation in spontaneously breathing rabbits supported by elastic and resistive unloading

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and in humans with lung disease. This study tests the hypothesis that PLV combined with respiratory mechanical unloading results in stable ventilation and gas exchange in spontaneously breathing animals. Ten adult anesthetized, intubated, and spontaneously breathing rabbits received ventilatory support by respiratory mechanical unloading (Fi(O2) 1.0). Minute ventilation, respiratory rate, esophageal pressure, heart rate, and arterial blood pressure were recorded continuously during gas ventilation for 1 h. Next, 30 mL/kg of perfluorocarbon was instilled into the endotracheal tube. Thereafter, data were recorded again for 1 h (PLV). Arterial blood gases were obtained at the end of each period. Variability of recorded data was assessed by calculating coefficients of variation using data obtained each minute. Compared with gas ventilation, minute ventilation was larger during PLV (275 +/- 93 versus 368 +/- 89 mL/kg/min.; p < 0.01). This was because of a higher respiratory rate during PLV (58 +/- 23 versus 74 +/- 18 breaths/min; p < 0.05), while tidal volume was similar. Compared with gas ventilation, Pa(O2) was lower during PLV (61.31 +/- 5.32 versus 47.35 +/- 8.38 kPa; p < 0.05). Pa(CO2), peak esophageal pressure deflections, heart rate, mean arterial blood pressure, and coefficients of variation for minute ventilation, tidal volume, respiratory rate, and peak esophageal pressure were not significantly different between modes. Compliance was decreased and resistance and work of breathing were increased during PLV. We conclude that stable ventilation and gas exchange may be achieved during PLV combined with mechanical unloading in spontaneously breathing animals without lung disease.     

Tracheal gas insufflation as a lung-protective strategy: physiologic, histologic, and biochemical markers.

OBJECTIVE: Conventional mechanical ventilation in acute lung failure potentiates lung injury, which can be assessed by physiologic, histologic, and biochemical markers. Thus, new ventilation strategies are directed at reducing lung injury. Tracheal gas insufflation has been shown to reduce endotracheal tube prosthetic deadspace and peak inspiratory pressure during conventional mechanical ventilation. Our objective was to use physiologic, histologic, and biochemical markers to test the hypothesis that tracheal gas insufflation in acute lung injury is lung protective. DESIGN: Animal experiment. SETTING: University setting. SUBJECTS: Juvenile rabbits (n = 12; 1.95 +/- 0.1 SE kg). INTERVENTIONS: Rabbits were anesthetized, instrumented, paralyzed, and ventilated with Fio(2) = 1.0. Lung injury was induced with repeated saline lavage (10 mL/kg per lavage until Pao(2) 相似文献   

Hyperoxia effects on pulmonary pressure: volume characteristics and lavage surfactant phospholipid in the newborn rabbit

The effect of hyperoxia (greater than 95%) on surfactant phospholipid recovered by lavage and pulmonary pressure:volume characteristics was studied in rabbits exposed from birth through 4 days of life. Decreased surfactant phospholipid (microgram/mg dry lung weight) in the airways was observed as early as 6 h and persisted through 96 h of life in hyperoxia-exposed animals. The composition of lavage phospholipids and fatty acid profile of phosphatidylcholine was not altered by hyperoxia. Pressure:volume analysis revealed a decrease in maximum lung distensibility (V30, volume at 30 cm pressure) at 48 and 96 h and a decrease in inflation compliance (P30i, pressure on inflation to 30% V30) at 48 h of life in newborn pups exposed to hyperoxia. Pressure:volume changes in both male and female newborns were observed with hyperoxia exposure. However, only female pups exhibited a decrease in lavage phospholipid content as measured at 48 h. These data suggest that the newborn rabbit surfactant system is susceptible to oxygen toxicity. In addition to age-related differences, sex differences may exist with regard to susceptibility to hyperoxia. Subtle alterations in the surfactant system at this critical time of rapid lung development could have long lasting effects on lung function.     

Therapeutic hypercapnia is not protective in the in vivo surfactant-depleted rabbit lung

Permissive hypercapnia because of reduced tidal volume is associated with improved survival in lung injury, whereas therapeutic hypercapnia-deliberate elevation of arterial Pco2-protects against in vivo reperfusion injury and injury produced by severe lung stretch. No published studies to date have examined the effects of CO2 on in vivo models of neonatal lung injury. We used an established in vivo rabbit model of surfactant depletion to investigate whether therapeutic hypercapnia would improve oxygenation and protect against ventilator-induced lung injury. Animals were randomized to injurious (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O) or protective ventilatory strategy (tidal volume, 5 mL/kg; positive end-expiratory pressure, 12.5 cm H2O), and to receive either control conditions or therapeutic hypercapnia (fraction of inspired CO2, 0.12). Oxygenation (alveolar-arterial O2 difference, arterial Po2), lung injury (alveolar-capillary protein leak, impairment of static compliance), and selected bronchoalveolar lavage and plasma cytokines (IL-8, growth-related oncogene, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha) were measured. Injurious ventilation resulted in a large alveolar-arterial O2 gradient, elevated peak airway pressure, increased protein leak, and impaired lung compliance. Therapeutic hypercapnia did not affect any of these outcomes. Tumor necrosis factor-alpha was not increased by mechanical stretch in any of the groups. Therapeutic hypercapnia abolished the stretch-induced increase in bronchoalveolar lavage monocyte chemoattractant protein-1, but did not affect any of the other mediators studied. Therapeutic hypercapnia may attenuate the impairment in oxygenation and inhibit certain cytokines. Because hypercapnia inhibits certain cytokines but does not alter lung injury, the pathogenic role of these cytokines in lung injury is questionable.     

Effects of metaproterenol on pulmonary mechanics, oxygenation, and ventilation in infants with chronic lung disease

Changes in pulmonary resistance, dynamic compliance, tidal volume, and transcutaneous PO2 and PCO2 after nebulized administration of metaproterenol were evaluated in eight newborn infants (birth weight 650 to 1060 g, gestational age 25 to 28 weeks) with chronic lung disease receiving mechanical ventilation. The infants were monitored continuously before and for 15 minutes after nebulization of metaproterenol during 3 consecutive days at mean age 34 days. There were significant increases in compliance, tidal volume, and tcPO2, and significant decreases in pulmonary resistance and tcPCO2. These data show that bronchospasm contributes significantly to the high pulmonary resistance in preterm infants with chronic lung disease and that metaproterenol is beneficial in the therapy of infants with chronic lung disease requiring mechanical ventilation.     

Pneumothorax and pulmonary intersticial emphysema: treatment with selective bronchial occlusion and high frequency ventilation

OBJECTIVE: Our purpose was to report the use of selective bronchial occlusion with a balloon catheter, associated with high frequency ventilation for a successful treatment of a persistent left hypertensive pneumothorax associated with left bronchopleural fistula and severe bilateral pulmonary intersticial emphysema.METHODS: A newborn infant of 20 hours of age was referred to our ICU for treatment of severe respiratory distress and hemodynamic failure after spontaneous hypertense left pneumothorax. Despite being submitted to conventional mechanical ventilation, volume resuscitation and vasoactive drugs infusion, the patient worsened. Therefore, he underwent selective occlusion of the main left bronchus, a measure that can be effective to interrupt gas flow to the affected lung in situations like lung injury with air leak. In order to avoid worsening intersticial emphysema and air leak, high frequency ventilation was associated. This method is characterized by very low tidal volume, lower than the rest functional capacity, and is indicated in acute respiratory failure associated with air leak syndrome.RESULTS: Selective left main bronchus occlusion and high frequency ventilation were successfully used to treat the patient who, after that, presented a favorable outcome with full hemodynamic and respiratory recovery.CONCLUSION: Selective left main bronchus occlusion permitted mechanical ventilation of the contralateral side and high frequency ventilation allowed adequate oxygenation and ventilation maintenance with decrease of the risk of lung injury and also allowed recovery from the interstitial emphysema.     

Alveolar recruitment promotes homogeneous surfactant distribution in a piglet model of lung injury.

Uneven distribution of exogenous surfactant contributes to a poor clinical response in animal models of respiratory distress syndrome. Alveolar recruitment at the time of surfactant administration may lead to more homogeneous distribution within the lungs and result in a superior clinical response. To investigate the effects of three different volume recruitment maneuvers on gas exchange, lung function, and homogeneity of surfactant distribution, we studied 35 newborn piglets made surfactant deficient by repeated airway lavage with warm saline. Volume recruitment was achieved by either a temporal increase in tidal volume or an increase in end-expiratory pressure during surfactant administration, yielding an increase in dynamic compliance of the respiratory system of 77% in the first group and an increase in functional residual capacity of 108% in the second group. A third group of piglets (all n = 7) received a combination of both volume recruitment maneuvers, with increases in dynamic compliance of the respiratory system of 100% and in functional residual capacity of 192%. Those animals subjected to increased tidal volume showed an improved surfactant response in terms of oxygenation, ventilation, lung volumes, lung mechanics, and homogeneity of surfactant distribution. Increased end-expiratory volume augmented the surfactant effect only to some extent. The combination of both volume recruitment maneuvers, however, needed lung volumes beyond total lung capacity (approximately 56 mL/kg), thus probably inducing early sequelae of ventilator-induced lung injury. We conclude that volume recruitment by means of increased tidal volumes at the time of surfactant administration leads to a superior surfactant effect owing to more homogeneous surfactant distribution within a collapsed lung.     

吸入一氧化氮对胎粪吸入综合征新生猪脑的保护作用

目的探讨机械通气下吸入一氧化氮（NO）对胎粪吸入综合征（MAS）新生猪脑不同部位胆碱能神经元的保护作用及对星形胶质细胞增殖的影响。方法 建立新生猪胎粪吸入模型,并予间歇正压通气,随机分为胎粪吸入组（n=10）和NO治疗组（n=4）,另设正常对照组（n=4）。HE染色计数大脑皮质、海马及基底节神经元细胞,免疫组化法检测皮层、海马及基底节胆碱乙酰基转移酶（ChAT）和胶质纤维酸性蛋白（GFAP）免疫阳性细胞数。结果 胎粪吸入组脑不同部位的神经元细胞和ChAT阳性细胞数均较正常对照组减少[神经元细胞：皮质（29.6±2.3）比（58.2±3.8）,海马（27.0±12.7）比（56.0±3.7）,基底节（25.0±4.6）比（56.0±4.6）;ChAT阳性细胞：皮质（16.7±3.9）比（38.3±9.0）,海马（17.5±2.7）比（34.3±11.6）,基底节（17.0±1.2）比（35.3±7.1）,P均〈0.01],GFAP阳性细胞数增多[皮质（54.8±11.0）比（22.0±5.5）,海马（54.9±14.7）比（21.0±1.7）,基底节（53.8±7.1）比（19.0±4.6）,P均〈0.001）]。NO治疗组神经元细胞数和ChAT阳性细胞数均多于胎粪吸入组,GFAP阳性细胞数少于胎粪吸入组,P均〈0.05。结论 新生猪MAS后吸入NO可减少脑不同部位胆碱能神经元的丢失及星形胶质细胞的增殖,提示吸入NO可能对MAS引起的脑损伤具有保护作用。     

Early pulmonary changes associated with high-frequency jet ventilation in newborn piglets

To assess the short-term effects of high-frequency jet ventilation (HFJV) on the neonatal lung, 28 newborn piglets were studied. Nine piglets were unventilated except during brief pulmonary measurements, nine animals were conventionally ventilated (arterial CO2 tension 35-45 torr, arterial O2 tension 70-80 torr) for 4 h, and 10 piglets were ventilated with HFJV for the same period. Pulmonary function was analyzed using a computerized technique and tracheobronchial aspirates were examined for biochemical indicators of lung injury; after 4 h, bronchoalveolar lavage was obtained for surfactant composition and activity, and lung sections were examined by light and electron microscopy. Results showed that HFJV provided adequate ventilation at lower inspiratory pressure compared with conventional ventilation (8.6 +/- 0.3 versus 13.8 +/- 1.3 cm H2O; p less than 0.01), while pulmonary mechanics did not vary significantly among the three animal groups. Tracheobronchial aspirates from HFJV animals had higher elastase activity versus unventilated piglets (118.5 +/- 14.1 versus 57.7 +/- 8.4 micrograms/mL; p less than 0.01), as well as higher albumin concentration versus unventilated animals (94.2 +/- 18.7 versus 23.2 +/- 6.5 micrograms/mL; p less than 0.01). In addition, there were small but statistically significant differences between all three groups in the distribution of surfactant phospholipids in bronchoalveolar lavage, although biophysical activity was normal. Scanning electron microscopy revealed flattening of Clara cells in the terminal bronchioles of HFJV animals due to loss of glycogen and secretory granules. These data indicate that despite lower peak inspiratory pressures, HFJV can cause subtle biochemical changes in lungs. Further studies are indicated to determine if these changes precede significant lung injury.     

Have changes in ventilation practice improved outcome in children with acute lung injury?

OBJECTIVES: To describe the changes that have occurred in mechanical ventilation in children with acute lung injury in our institution over the last 10-15 yrs and to examine the impact of these changes, in particular of the delivered tidal volume on mortality. DESIGN: Retrospective study. SETTING: University-affiliated children's hospital. PATIENTS: The management of mechanical ventilation between 1988 and 1992 (past group, n = 79) was compared with the management between 2000 and 2004 (recent group, n = 85). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The past group patients were ventilated with a significantly higher mean tidal volume (10.2 +/- 1.7 vs. 8.1 +/- 1.4 mL.kg actual body weight, p < .001), lower levels of positive end-expiratory pressure (6.1 +/- 2.7 vs. 7.1 +/- 2.4 cm H2O, p = .007), and higher mean peak inspiratory pressure (31.5 +/- 7.3 vs. 27.8 +/- 4.2 cm H2O, p < .001) than the recent group patients. The recent group had a lower mortality (21% vs. 35%, p = .04) and a greater number of ventilator-free days (16.0 +/- 9.0 vs. 12.6 +/- 9.9 days, p = .03) than the past group. A higher tidal volume was independently associated with increased mortality (odds ratio 1.59; 95% confidence interval 1.20, 2.10, p < .001) and reduction in ventilation-free days (95% confidence interval -1.24, -0.77, p < .001). CONCLUSIONS: The changes in the clinical practice of mechanical ventilation in children in our institution reflect those reported for adults. In our experience, mortality among children with acute lung injury was reduced by 40%, and tidal volume was independently associated with reduced mortality and an increase in ventilation-free days.     

小潮气量常规机械通气对发育肺生长因子和炎症因子表达的影响

目的：探讨小潮气量常规机械通气对发育肺生长因子（GFs）和炎症因子表达的影响。方法：分别将早产猪（85％孕龄）、足月新生猪及幼猪（4~5周龄）随机分为机械通气组（MV组）和自主呼吸对照组（NMV组）。调节呼吸机参数,使呼出气潮气量维持在6～8 mL/kg,机械通气6 h（早产猪）或24 h（新生猪、幼猪）后检测肺组织GFs（PDGF-B,IGF-I,KGF,HGF,VEGF,TGF-β1）及炎症因子（IL-1β,IL-6,IL-8,TNF-α）mRNA表达,免疫组化方法观察GFs蛋白表达与分布。多组间比较用单因素方差分析或Kruskal-Wallis检验,两组间比较用t检验或Mann-Whitney U检验。结果：①在早产组,MV组PDGF-B,IL-1β,IL-6,IL-8 mRNA水平较NMV组增高（5.11±0.10 vs 4.88±0.01, 4.95±0.27 vs 4.08±0.37, 4.76±0.27 vs 4.00±0.28, 5.31±0.57 vs 4.15±0.46; P<0.01或0.05）,IGF-I mRNA水平降低（3.54±0.13 vs 3.80±0.11; P<0.01）;②在足月新生组及幼年组,MV组GFs及炎症因子mRNA水平较NMV组差异均无显著性。结论： 生后早期机械通气干扰了早产肺GFs的表达,并诱发促炎因子表达,促进了肺损伤的发生;但对足月和幼年肺GFs和炎症因子表达无明显影响。     

Sublethal endotoxemia promotes pulmonary cytokine-induced neutrophil chemoattractant expression and neutrophil recruitment but not overt lung injury in neonatal rats

Gram-negative sepsis and septic shock remain major causes of morbidity and mortality in the newborn. Respiratory failure is a common feature in neonatal sepsis regardless of the presence or absence of associated pneumonia. In adult animal models, cytokine-induced neutrophil chemoattractant (CINC) is a potent chemoattractant for neutrophils and believed to play a role in endotoxin-induced lung injury. We examined this in a neonatal model. Ten-day-old Sprague-Dawley rats were injected with Salmonella enteritidis endotoxin (ETX) 0.03 mg/kg i.p. and sacrificed at baseline, 30 min, 1, 2, 4, 8 and 16 h post-ETX. Blood was collected by cardiac puncture. After bronchoalveolar lavage, lung tissue was collected and evaluated for neutrophil (polymorphonuclear leukocyte) recruitment by myeloperoxidase assay (MPO). Lung CINC expression was measured by Northern blot and ELISA. Peripheral blood leukocytosis was noted at 1 h (p < 0.001) with counts below baseline at 2 and 4 h. Differential counts revealed neutrophilia at 8 h (p < 0.001). MPO revealed pulmonary PMN recruitment peaking at 1 h (p < 0.05) and CINC RNA and protein expression peaked slightly later at 2 h (p < 0. 001). No overt lung injury was noted by bronchoalveolar lavage cell counts or by histology. Therefore, pulmonary CINC expression and neutrophil recruitment follows LPS exposure in neonatal rats. This may represent priming of the lung tissue and a secondary event may be necessary for injury to occur.