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。     

促炎症细胞因子对新生猪肺泡Ⅱ型上皮细胞相关生长因子表达的影响

目的 建立出生后1～3 d新生猪肺泡Ⅱ型上皮细胞(AEC-Ⅱ)体外分离纯化及鉴定方法,探讨促炎症细胞因子对AEC-Ⅱ长因子(GFs)的影响,比较不同消化酶溶液、纯化方法获得细胞产量、活力及AEC-Ⅱ纯度的差异.方法 原代培养AEC-Ⅱ24 h给予不同浓度IL-1β、IL-6刺激48 h,观察AEC-Ⅱ增殖变化,RT-PCR检测胰岛素样生长因子-1(IGF-Ⅰ)、血小板源性生长因子(PDGF)、表面活性物质蛋白(SP)-A及-B mRNA的表达情况,并检测IGF-Ⅰ抗体对AEC-Ⅱ增殖及SP-A、SP-B mRNA表达的影响.结果 30000 U/L弹力蛋白酶/0.1%胰酶在37℃下消化新生猪肺组织20 min获得细胞产量为(5.33±0.54)×106/g(肺重+心重),显著高于其他各组(P<0.01).免疫黏附法纯化AEC-Ⅱ产量明显高于Percoll法,为(38.0±28.0)×106/头新生猪.AEC-Ⅱ原代培养24～96 h状态最佳.随IL-1β、IL-6刺激浓度升高,AEC-Ⅱ增殖能力及IGF-Ⅰ及SP-A mRNA表达水平降低,但PDGF、SP-B mRNA的表达无明显变化.IGF-Ⅰ抗体刺激下,AEC-Ⅱ增殖能力及SP-A、SP-B mRNA表达水平均降低.结论 IL-1B、IL-6可能通过调节AEC-Ⅱ中IGF-Ⅰ mRNA的表达影响细胞的增殖及功能.     

Responses of pulmonary platelet-derived growth factor peptides and receptors to hyperoxia and nitric oxide in piglet lungs

The peptides platelet-derived growth factor-A (PDGF-A) and especially -B have important roles in lung development. The effect of hyperoxic exposure with and without inhaled nitric oxide (iNO) on lung expression of PDGF and its receptors is unknown. We hypothesized that hyperoxia exposure would suppress mRNA expression and protein production of these ligands and their receptors. The addition of iNO to hyperoxia may further aggravate the effects of hyperoxia. Thirteen-day-old piglets were randomized to breathe 1) room air (RA); 2) 0.96 fraction of inspired oxygen (O2), or 3) 0.96 fraction of inspired oxygen plus 50 ppm of NO (O2+NO), for 5 d. Lungs were preserved for mRNA, Western immunoblot, and immunohistochemical analyses for PDGF-A and -B and their receptors PDGFR-alpha and -beta. PDGF-B mRNA expression was greater than that of PDGF-A or PDGFR-alpha and -beta in RA piglet lungs (p<0.05). Hyperoxia with or without iNO reduced lung PDGF-B mRNA and protein expression relative to the RA group lungs (p<0.01). PDGF-B immunostain intensity was significantly increased in the alveolar macrophages, which were present in greater numbers in the hyperoxia-exposed piglet lungs, with or without NO (p<0.01). PDGFR-beta immunostaining was significantly increased in airway epithelial cells in O2- and O2+NO-exposed piglets. PDGF-A and PDGFR-alpha immunostain intensity and distribution pattern were unchanged relative to the RA group. Sublethal hyperoxia decreases PDGF-B mRNA and protein expression but not PDGF-A or their receptors in piglet lungs. iNO neither aggravates nor ameliorates this effect.     

The effect of endurance-type exercise training on growth mediators and inflammatory cytokines in pre-pubertal and early pubertal males

Recent studies demonstrate an unexpected reduction in circulating levels of IGF-I after 5 wk of endurance-type exercise training in adolescent boys and girls and prepubertal girls. We hypothesized that the reduction in IGF-I would be accompanied by a training-associated stimulation of proinflammatory cytokines IL-1beta, IL-6, or tumor necrosis factor-alpha (TNF-alpha), each of which can inhibit the GH-->IGF-I axis. Healthy boys (age range 9-11 y old, mean Tanner 1.7) volunteered for the study and were randomized to control (n = 14) and training groups (n = 12) for 5 wk. After the intervention, significant increase in fitness was observed in the training group but not control group. Although IGF-I was correlated at baseline to peak oxygen consumption in all subjects, there was a significant decrease in IGF-I and IGF binding protein-3 in the training subjects (-12.8 +/- 7.3% and -17.5 +/- 7%, respectively, p < 0.05). In contrast, IGF binding protein-2, known to inhibit anabolic effects of IGF-I, increased in the training subjects (27.8 +/- 11%, p < 0.02) as did IL-1beta and TNF-alpha (51.5 +/- 30.22%, p < 0.02, and 44.5 +/- 23.2%, p < 0.02, respectively). Finally, we also found that GHBP was inversely correlated with fitness, suggesting altered GH function in more-sedentary boys. Thus, these data support the hypothesis that a sustained increase in physical activity can stimulate proinflammatory cytokines, which may contribute to suppression of the GH-->IGF-I axis. Physical activity can influence growth and development through its influence on anabolic and catabolic mediators.     

Lung inflammatory responses to intratracheal interleukin-1alpha in ventilated preterm lambs

Interleukin-1alpha is an early response proinflammatory cytokine that has been associated with chorioamnionitis and preterm labor, brain injury, and bronchopulmonary dysplasia. However, IL-1alpha also can increase expression of surfactant proteins and induce lung maturation in the preterm fetus. We measured the effects of IL-1alpha given by intratracheal instillation (IT) and compared the responses with injection of i.v. IL-1alpha in surfactant-treated and ventilated premature lambs. IT recombinant ovine IL-1alpha at doses of 5 and 50 microg/kg caused a similar large recruitment of neutrophils into the bronchoalveolar lavage fluid. The neutrophils expressed CD11b, CD14, and CD44, but did not produce increased amounts of H(2)O(2). Cells from the bronchoalveolar lavage fluid had increased expression of proinflammatory cytokines, which also were increased in mRNA from lung tissue. The IT IL-1alpha also suppressed the expression of surfactant protein-C mRNA. Systemic effects were decreased neutrophils in blood, decreased lung function, increased heart rate, and hypotension or death in the 50 microg/kg IL-1alpha IT group and only decreased neutrophils in the blood in the 5 microg/kg IL-1alpha IT group. The i.v. IL-1alpha caused no lung inflammation or injury but did result in severe neutropenia and hypotension leading to early death. IT IL-1alpha can cause intense lung inflammation and systemic shock in ventilated preterm lungs.     

Postnatal lung inflammation increased by ventilation of preterm lambs exposed antenatally to Escherichia coli endotoxin

Chorioamnionitis resulting in exposure of the fetal lung to inflammation is frequent before preterm delivery. The initiation of mechanical ventilation in the preterm recruits granulocytes to the lungs and increases proinflammatory cytokine expression in the lungs. We hypothesized that when the prematurely born newborn with chorioamnionitis was ventilated, inflammation would increase. Therefore, we asked whether inflammatory exposure to the fetal lung caused by intra-amniotic endotoxin (10 mg, Escherichia coli 055:beta 5) given at 100 d gestation would alter the inflammatory responses to the mechanical ventilation in surfactant-treated preterm lambs delivered at 130 d gestation. Cells in alveolar washes, proinflammatory cytokine expression, and surfactant protein mRNA expression were not different for saline and endotoxin exposed lambs that were not ventilated. The endotoxin- and saline-exposed control animals had similar lung function for 6 h of ventilation. Bronchoalveolar lavage fluid from the ventilated and antenatal endotoxin-exposed animals contained 5.7 times more monocytes, 12 times more lymphocytes, and a nonsignificant increase in neutrophils. Cells from the bronchoalveolar lavage fluid expressed 3-fold more IL-6 and IL-8 mRNA than did cells from the saline exposed comparison animals. An antenatal exposure of the fetal lung to endotoxin enhanced the subsequent inflammatory response of the ventilated preterm lung.     

High frequency oscillatory ventilation suppresses inflammatory response in lung tissue and microdissected alveolar macrophages in surfactant depleted piglets

The impact of high frequency oscillatory ventilation (HFOV) compared with intermittent mandatory ventilation (IMV) on oxygenation and pulmonary inflammatory response was studied in a surfactant depleted piglet model. After establishment of lung injury by bronchoalveolar lavage, piglets either received HFOV (n =5) or IMV (control; n = 5) for eight hours. PaO(2) was higher and mean pulmonary arterial pressure (MPAP) was lower with HFOV (HFOV versus control, mean +/- SEM; endpoint PaO(2): 252 +/- 73 versus 68 +/- 8.4 mm Hg; p < 0.001; MPAP: 22 +/- 2.3 versus 34 +/- 2.5 mm Hg; p < 0.01). mRNA expression of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, TGF-beta 1, Endothelin-1, and adhesion molecules (E-selectin, P-selectin, ICAM-1) in lung tissue was quantified by real time PCR normalized to beta-actin and hypoxanthine-guanine-phosphoribosyl-transferase (HPRT). mRNA expression of all cytokines and adhesion molecules/HPRT was higher in controls (e.g.: HFOV versus control, mean +/- SEM; IL-1 beta/HPRT: 1.6 +/- 0.3 versus 23.1 +/- 8.6 relative units (RU), p < 0.001; IL-8/HPRT: 8.5 +/- 2.0 versus 63.5 +/- 15.2 RU, p < 0.001). IL-8/HPRT gene expression was quantified in microdissected single cells. With HFOV, IL-8 gene expression was highly reduced in alveolar macrophages: 10 +/- 3.4 copies IL-8 mRNA/copy HPRT mRNA versus 356 +/- 142; p < 0.05 (bronchiolar epithelial cells: 33 +/- 16 versus 208 +/- 108; alveolar septum: 2.1 +/- 1.3 versus 26 +/- 11; bronchiolar smooth muscle cells: 1.3 +/- 0.3 versus 2.8 +/- 1.0; vascular smooth muscle cells: 0.7 +/- 0.3 versus 1.1 +/- 0.4). In conclusion, HFOV improved oxygenation, reduced pulmonary arterial pressure and attenuated pulmonary inflammatory response.     

Effect of exercise on cytokines and growth mediators in prepubertal children.

Many of the anabolic effects of exercise are mediated through insulin-like growth factor-I (IGF-I), but in adolescents, brief exercise training leads to reductions, rather than the expected increase, in circulating IGF-I. Certain cytokines--interleukin-(IL) 1beta (IL-1beta), IL-6 (IL-6), and tumor necrosis factor-alpha--are increased by exercise in adults and are known to inhibit IGF-I. To test the hypothesis that these cytokines might play a role in the adaptation to exercise, we measured the acute effects of exercise on selected cytokines and growth factors in 17 healthy 8- to 11-y-old children (4 females). Designed to mimic patterns and intensity of exercise found in the real lives of American children, the exercise protocol consisted of a 1.5-h soccer practice (of which about 40 min constituted of vigorous exercise). Pre- and postexercise urine and saliva samples were obtained in all subjects and both blood and urine in nine subjects. The exercise led to significant increases in circulating tumor necrosis factor-alpha (18 +/- 7%, p < 0.05) and IL-6 (125 +/- 35%, p < 0.01) as well as a significant increase in the antiinflammatory cytokine IL-1 receptor antagonist (33 +/- 10%, p < 0.01). Urine levels of IL-6 were also substantially increased by exercise (440 +/- 137%, p < 0.0001). Circulating levels of IGF-I were reduced to a small but significant degree (-6.4 +/- 3.2%, p < 0.05), although IGF-binding protein-1 (known to inhibit IGF-I) was substantially increased (156 +/- 40%, p < 0.001). Cytokines are systemically increased after relatively brief exercise in healthy children. This increase may alter critical anabolic agents such as IGF-I and its binding proteins.     

Positive end-expiratory pressure modifies response to recombinant and natural exogenous surfactant in ventilated immature newborn rabbits

BACKGROUND AND OBJECTIVES: Different types of surfactant preparations were shown not to exert uniform response in preterm infants suffering from respiratory distress syndrome (RDS). Therefore, the effects of a recombinant surfactant protein C (rSP-C) based preparation and a natural surfactant were compared applying different levels of positive end-expiratory pressure (PEEP) in experimental RDS. METHODS: Preterm rabbits (n = 7-14 per group; 27 days gestation; term 30 days) were randomized for receiving either 100 mg/kg rSP-C or natural bovine surfactant and were compared with saline treated controls. Animals were ventilated for 30 min with either 0.3 or 0 kPa PEEP at standardized tidal volumes and lung mechanics were measured as well as lung histology and mRNA expression of surfactant associated proteins B and C by real-time PCR. RESULTS: The PEEP level applied (0.3 vs. 0 kPa) largely influenced dynamic compliance after administration of rSP-C surfactant (4.45 vs. 2.58 ml/kg), whereas natural surfactant improved compliance regardless of the PEEP applied (4.86 vs. 4.24 ml/kg) compared to controls (2.41 vs. 1.55 ml/kg). Accordingly, administration of PEEP significantly increased alveolar count in all groups as well as SP-C mRNA expression, whereas SP-B expression and protein content both remained unchanged. CONCLUSION: Response to rSP-C surfactant depends on the PEEP level applied in our model of neonatal RDS. These findings should be considered for the conception of clinical trials regarding treatment strategies in neonatal RDS.     

Aerosolized perfluorocarbon suppresses early pulmonary inflammatory response in a surfactant-depleted piglet model.

The effect of new ventilation strategies on initial pulmonary inflammatory reaction was studied in a surfactant-depleted piglet model. Sixty minutes after induction of lung injury by bronchoalveolar lavage, piglets received either aerosolized FC77 (aerosol-PFC, 10 mL/kg/h, n = 5) or partial liquid ventilation (PLV) with FC77 at functional residual capacity volume (FRC-PLV, 30 mL/kg, n = 5), or at low volume (LV-PLV, 10 mL/kg per hour, n = 5), or intermittent mandatory ventilation (control, n = 5). After 2 h, perfluorocarbon application was stopped and intermittent mandatory ventilation continued for 6 h. After a total experimental period of 8 h, animals were killed and lung tissue obtained. mRNA expression of IL-1beta, IL-6, IL-8, and TGF-beta in porcine lung tissue was quantified using TaqMan real-time PCR and normalized to beta-actin (A) and hypoxanthine-guanine-phosphoribosyl-transferase (H). In the aerosol-PFC group, IL-1beta, IL-6, IL-8, and transforming growth factor (TGF)-beta mRNA expression in lung tissue was significantly lower than in the control group. Reduction was 95% for IL-1beta/H (p < 0.001), 73% for IL-6/H (p < 0.05), 87% for IL-8/H (p < 0.001), and 38% for TGF-beta/H (p < 0.01). A lower mRNA gene expression was also determined for IL-1beta and IL-8 when the aerosol-PFC group was compared with the LV-PLV group [91% for IL-1beta/H (p < 0.001), 75% for IL-8/H (p < 0.001)]. In the FRC-PLV group, mRNA expression of IL-1beta was significantly lower than in the control (p < 0.05) and LV-PLV (p < 0.01) group. In a surfactant-depleted piglet model, aerosol therapy with perfluorocarbon but not LV-PLV reduces the initial pulmonary inflammatory reaction at least as potently as PLV at FRC volume.     

Cytokine expression of cord and adult blood mononuclear cells in response to Streptococcus agalactiae

Neonatal bacterial sepsis is often characterized by a fulminant clinical course and highly elevated plasma levels of proinflammatory cytokines. To evaluate in vitro activation of the neonatal immune system by specific infectious stimuli, cord blood cells from healthy neonates were examined for expression of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, and IL-8 in response to Streptococcus agalactiae (GBS), lipopolysaccharide (LPS), and lipoteichoic acid (LTA). Cytokine-expression was compared in mononuclear cells from cord and adult peripheral blood. TNF-alpha and IL-6 levels in the supernatant of cord blood cell cultures were significantly higher after stimulation with heat-killed GBS (10(7)/mL) than with LPS (2 microg/mL) or LTA (2 microg/mL) (TNF-alpha: 2215 versus 267.5 versus 40 pg/mL, p = 0.001; IL-6: 9667 versus 4909 versus 919 pg/mL, p = 0.006). mRNA expression of TNF-alpha, IL-1beta, IL-6, and IL-8 was equally pronounced after stimulation with either GBS, LPS, or LTA in cord or adult blood cells at various times. A MAb directed against the monocyte receptor molecule CD14 did not inhibit the release of cytokines in cord blood mononuclear cells after stimulation with GBS. In summary, activation of cord blood cells by infectious stimuli is comparable to the adult immune response in terms of expression of proinflammatory cytokines. GBS in particular proves to be a potent activator of the neonatal immune system when compared with LPS and LTA. CD14 seems not to be a crucial molecule for activation of cord blood cells by GBS.     

Injury responses to different surfactants in ventilated premature lamb lungs

The lung of the preterm infant is easily injured and an initial indication of the injury is an inflammatory response. Surfactant treatment and gentle ventilation will minimize the initiation and progression of injury. We asked if the initial lung injury response differed when preterm ventilated lambs were treated with complete natural sheep surfactant, a lipid extract of sheep surfactant, a surfactant used to treat RDS (Survanta), or a synthetic surfactant containing recombinant SP-C (Venticute). We used a gentle style of ventilation and a positive end expiratory pressure of 4 cmH(2)0 to minimize injury. The surfactants were not distinguishable based on gas exchange, compliance or lung gas volumes over the 6h ventilation period. When compared with unventilated controls the ventilated lambs had increased protein and inflammatory cells in alveolar lavages. The cells from the alveolar lavages produced more H(2)0(2), expressed more surface adhesion antigens and CD-14 receptors, and expressed more mRNA for the pro-inflammatory cytokines IL-1 beta and IL-8 than did cells from unventilated lungs. Lung tissue expressed primarily increased IL-6 mRNA relative to unventilated controls. However, there were no consistent differences in any of the inflammatory indicators between the different surfactant treated groups. Because endotoxin free natural surfactant containing SP-A was not superior to three other surfactants containing differing amounts of the surfactant proteins, additions of these proteins to clinical surfactants may not decrease the indicators of lung inflammation that accompany the initiation of ventilation of the preterm lung.     

KGF and FGF-10 stimulate liquid secretion in human fetal lung.

During fetal life, the pulmonary epithelium secretes liquid that distends the airways and is important for normal lung growth and development. The factors regulating human fetal lung liquid secretion are poorly understood; however, recent studies in murine models show that keratinocyte growth factor (KGF, FGF-7) and fibroblast growth factor 10 (FGF-10) stimulate liquid secretion. We asked whether KGF and FGF-10 stimulate liquid secretion in human fetal lung. First trimester fetal lung explants developed dose-dependent increases in intraluminal volume in response to KGF and FGF-10. Although there were no acute changes in explant transepithelial potential difference in response to KGF (0.1-1000 ng/mL), exposure to 5-50 ng/mL KGF over 60 h depolarized transepithelial potential difference compared with controls. We used ribonuclease protection assays to quantitate the ontogeny and regulation of mRNA expression for KGF and its receptor. Both mRNA were expressed in fetal and postnatal lung. Because the promoter region of the human KGF gene contains cAMP and IL-6 response elements, we asked whether cAMP or IL-6 stimulated expression of KGF or its receptor. We have previously shown that cAMP stimulates liquid secretion in this model. Both cAMP and IL-6 significantly increased expression of KGF but not KGF receptor during a 48-h experiment. Thus, stimulation of liquid secretion in explant models by cAMP may be mediated in part by induction of KGF expression. KGF and FGF-10 may be important paracrine factors regulating liquid secretion in human fetal lung.     

肺表面活性物质和吸入一氧化氮治疗家兔胎粪吸入性肺损伤

目的　观察在应用肺表面活性物质 (Surf)和吸入一氧化氮 (NO)预防性治疗家兔胎粪吸入性急性肺损伤 (ALI)并机械通气时的疗效。方法　将 3 3只成年家兔随机分为 5组进行治疗 :即对照组 (C ,n =8)、NO组 (n =6)、Surf组 (n =7)、NO +Surf组 (SNO ,n =6)、正常组 (N ,n =6)。前四组用胎粪生理盐水混悬液滴入气道内经机械通气造成ALI并随机分四组治疗 ;N组气道内滴入生理盐水替代 ;NO组连续吸入NO 1× 10 - 6 、10× 10 - 6 、2 0× 10 - 6 、40× 10 - 6 各 1h ,间隔停用 3 0min ;Surf组气道内滴入猪肺Surf10 0mg/kg ;SNO组联合NO吸入及Surf组治疗 ,各组均治疗 6h ,同时测定血气、肺呼吸力学判断疗效。化学发光法检测吸入气NO浓度。结果　在C组胎粪滴入 3 0min后动脉血氧合 (PaO2 /FiO2 )及呼吸顺应性 (DynamicCompliance ,Cdyn)显著变差 ,治疗后血氧合、Cdyn在SNO组显著改善 ,Surf和NO组略有改善。在湿化器前持续接入NO可在供气管道“Y”近端测得较为稳定的吸入NO浓度 ,受呼出气的影响最小 ,( 10～ 2 0 )× 10 - 6 NO吸入有较好的效果。结论　Surf联合NO治疗在有效预防ALI上优于单独应用Surf或NO。从呼吸机供气管路持续接入NO测定到稳定NO浓度与接入气和监测部位有关     

Meconium is a source of pro-inflammatory substances and can induce cytokine production in cultured A549 epithelial cells

Inflammation plays an important role in the pathogenesis of meconium aspiration syndrome, and pneumonitis is one of the major characteristics. We have previously shown that meconium has chemotactic properties because of the presence of IL-8. We hypothesize that IL-8 and other proinflammatory substances in meconium may amplify inflammation in meconium aspiration syndrome, inducing endogenous cytokine production by lung epithelial cells. We measured proinflammatory substances in first-pass meconium from healthy newborns and evaluated the effect of sterile meconium on cytokine production in cultured A549 alveolar epithelial cells in vitro. IL-1beta, IL-6, IL-8, and tumor necrosis factor-alpha were measured by ELISA, and heme was measured spectrophotometrically. After incubation of meconium samples with A549 cells, cytokine concentrations in the supernatant were measured. Meconium samples contained variable amounts of IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and heme. On stimulation of A549 cells with meconium, the IL-8 concentration in the culture supernatant significantly increased above baseline measurements, whereas tumor necrosis factor-alpha showed a variable pattern and IL-1beta or IL-6 remained unchanged. There was no quantitative relationship between the concentration of the measured cytokines and heme in meconium and cytokine release by the A549 cells after meconium exposure. Meconium contains proinflammatory substances. All samples induced IL-8 release and some induced tumor necrosis factor-alpha release in cultured A549 epithelial cells. We speculate that proinflammatory substances in meconium can induce lung inflammation in meconium aspiration syndrome in two ways: directly via cytokines and heme present in meconium and indirectly by inducing cytokine release by the epithelial lung cells.     

机械通气对小儿体外循环术后IL-6 IL-10及TNF-α的影响

目的：体外循环（CPB）术造成全身炎症因子水平升高,机械通气可能对其水平有一定影响。该文探讨不同机械通气模式对小儿CPB术后炎症因子的影响,为临床治疗提供参考。方法：60例CPB术后小儿随机分为A组和B组,每组30例,A组术后接受高潮气量-低PEEP机械通气,B组接受低潮气量-高PEEP机械通气,比较两组血浆中IL-6,IL-10及TNF-α的水平在不同时间点的差异。结果：两组患儿炎症因子在CPB结束时显著增高,在术后1 h达到峰值。术后1 h和6 h,A组炎症因子水平均高于B组。结论：不同的机械通气模式对CPB术后全身炎症因子水平有一定影响,低潮气量-高PEEP模式显著降低炎症因子水平。     

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.     

Contribution of pulmonary surfactant with inhaled nitric oxide for treatment of pulmonary hypertension

BACKGROUND: Combined therapy of inhaled nitric oxide (iNO) with pulmonary surfactant replacement was reported to improve oxygenation in patients or animal models of persistent pulmonary hypertension of the newborn with pulmonary surfactant deficiency lung. To evaluate the potential of iNO for the treatment of persistent pulmonary hypertension of the newborn, pulmonary arterial pressure (PAP) was measured during iNO before and after pulmonary surfactant replacement in an animal model of pulmonary hypertension with surfactant deficiency. METHODS: Seven newborn piglets were injected with L-nitro-arginine-methylester to produce an animal model of pulmonary hypertension. After PAP increased, iNO (30 p.p.m.) was introduced. Then iNO was stopped, and animals were subjected to lung lavage with saline. After recording the effect of iNO, all animals then received exogenous pulmonary surfactant installation. After surfactant treatment, iNO was again introduced. RESULTS: Pulmonary arterial pressure and systemic arterial pressure were increased significantly by >30% after infusion of L-nitro-arginine-methylester. During iNO only PAP was reduced significantly. Respiratory system compliance decreased significantly after lung lavage, and increased significantly after pulmonary surfactant replacement with concomitant increase of PaO2. In contrast, significant reduction of PAP with iNO before and after pulmonary surfactant replacement were also observed. The reduction ratios of PAP under each condition were 75.2 +/- 7.4%, 81.3 +/- 3.1%, and 79.1 +/- 5.3%, respectively (not significant among conditions). CONCLUSION: These results suggest that iNO is still a potent pulmonary arterial vasodilator even under pulmonary surfactant deficiency in an animal model of pulmonary hypertension.