Neutrophils play a critical role in ventilation-induced lung injury. This study was aimed to investigate the characteristics of neutrophils influx in lungs induced by high tidal volume ventilation. Anaesthetized rats ...Neutrophils play a critical role in ventilation-induced lung injury. This study was aimed to investigate the characteristics of neutrophils influx in lungs induced by high tidal volume ventilation. Anaesthetized rats were randomly divided into low tidal volume ventilation group (Vt: 7 mL/kg, LV group) or high tidal volume ventilation group (Vt:42mL/kg, HV group ) (n=40 in each). Rats in each group were ventilated for 0, 60, 90, 120 and 240 min. The wet/dry lung weight ratio (W/D) was measured. The levels of macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α), and the activity of myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA). The number of neutrophils in bronchoalveolar lavage fluid (BALF) was counted after Wright’s staining, and the percentage of netrophils in lung tissues calculated. Histopatholgical examination was used to observe the changes of lung tissues after different ventilations. The results showed that the W/D weight ratio was increased, and the levels of MIP-2 and TNF-α significantly enhanced in HV group at 90, 120 and 240 min. Neutrophils in BALF and the neutrophil percentage in lung tissues were also elevated at 120 and 240 min, which coincided with the enhanced activity of MPO in HV group. The lung injury was significantly related with the ventilation time and the infiltration of neutrophils in lungs in HV group. In conclusion, in ventilation-induced lung injury, neutrophil infiltration is present in a time-dependent manner and associated with the aggravated lung injury. Pulmonary structural damage may be the main reason for ventilation-induced lung injury.展开更多
Expiratory flow limitation(EFL), that is the inability of expiratory flow to increase in spite of an increase of the driving pressure, is a common and unrecognized occurrence during mechanical ventilation in a variety...Expiratory flow limitation(EFL), that is the inability of expiratory flow to increase in spite of an increase of the driving pressure, is a common and unrecognized occurrence during mechanical ventilation in a variety of intensive care unit conditions. Recent evidence suggests that the presence of EFL is associated with an increase in mortality, at least in acute respiratory distress syndrome(ARDS) patients, and in pulmonary complications in patients undergoing surgery. EFL is a major cause of intrinsic positive end-expiratory pressure(PEEPi), which in ARDS patients is heterogeneously distributed, with a consequent increase of ventilation/perfusion mismatch and reduction of arterial oxygenation. Airway collapse is frequently concomitant to the presence of EFL.When airways close and reopen during tidal ventilation, abnormally high stresses are generated that can damage the bronchiolar epithelium and uncouple small airways from the alveolar septa, possibly generating the small airways abnormalities detected at autopsy in ARDS. Finally, the high stresses and airway distortion generated downstream the choke points may contribute to parenchymal injury, but this possibility is still unproven. PEEP application can abolish EFL, decrease PEEPi heterogeneity, and limit recruitment/derecruitment.Whether increasing PEEP up to EFL disappearance is a useful criterion for PEEP titration can only be determined by future studies.展开更多
BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortalit...BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries （VILI） and to explore its potential mechanisms.METHODS： Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope.RESULTS： IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-a ray degree of group B was significantly higher than that in the other groups （P〈0.01）, especially in group C （P〉0.05）. The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B.CONCLUSION： Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.展开更多
Driving pressure(ΔP)is a core therapeutic component of mechanical ventilation(MV).Varying levels ofΔP have been employed during MV depending on the type of underlying pathology and severity of injury.However,ΔP lev...Driving pressure(ΔP)is a core therapeutic component of mechanical ventilation(MV).Varying levels ofΔP have been employed during MV depending on the type of underlying pathology and severity of injury.However,ΔP levels have also been shown to closely impact hard endpoints such as mortality.Considering this,conducting an in-depth review ofΔP as a unique,outcome-impacting therapeutic modality is extremely important.There is a need to understand the subtleties involved in making sureΔP levels are optimized to enhance outcomes and minimize harm.We performed this narrative review to further explore the various uses ofΔP,the different parameters that can affect its use,and how outcomes vary in different patient populations at different pressure levels.To better utilizeΔP in MV-requiring patients,additional large-scale clinical studies are needed.展开更多
Independent lung ventilation,though infrequently used in the critical care setting,has been reported as a rescue strategy for patients in respiratory failure resulting from severe unilateral lung pathology.This involv...Independent lung ventilation,though infrequently used in the critical care setting,has been reported as a rescue strategy for patients in respiratory failure resulting from severe unilateral lung pathology.This involves isolating and ventilating the right and left lung differently,using separate ventilators.Here,we describe our experience with independent lung ventilation in a patient with unilateral diffuse alveolar hemorrhage,who presented with severe hypoxemic respiratory failure despite maximal ventilatory support.Conventional ventilation in this scenario leads to preferential distribution of tidal volume to the nondiseased lung causing over distension and inadvertent volume trauma.Since each lung has a different compliance and respiratory mechanics,instituting separate ventilation strategies to each lung could potentially minimize lung injury.Based on review of literature,we provide a detailed description of indications and procedures for establishing independent lung ventilation,and also provide an algorithm for management and weaning a patient from independent lung ventilation.展开更多
Objective：Mechanical ventilation （MV） has long been used as a life-sustaining approach for several decades.However,researchers realized that MV not only brings benefits to patients but also cause lung injury if use...Objective：Mechanical ventilation （MV） has long been used as a life-sustaining approach for several decades.However,researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly,which is termed as ventilator-induced lung injury （VILI）.This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms.Data Sources：This review was based on articles in the PubMed database up to December 2017 using the following keywords：＂ventilator-induced lung injury＂,＂pathogenesis＂,＂mechanism＂,and ＂biotrauma＂.Study Selection：Original articles and reviews pertaining to mechanisms of VILI were included and reviewed.Results：The pathogenesis of VILI was defined gradually,from traditional pathological mechanisms （barotrauma,volutrauma,and atelectrauma） to biotrauma.High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas,volutrauma,and atelectrauma.In the past two decades,accumulating evidence have addressed the importance of biotrauma during VILI,the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release,reactive oxygen species production,complement activation as well as mechanotransduction.Conclusions：Barotrauma,volutrauma,atelectrauma,and biotrauma contribute to VILI,and the molecular mechanisms are being clarified gradually.More studies are warranted to figure out how to minimize lung injury induced by MV.展开更多
Background： Ventilator-induced lung injury （VILI） is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated, This study e...Background： Ventilator-induced lung injury （VILI） is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated, This study examined the relationship between inflammatory cytokines （interleukin JILl-6, tumor necrosis factor [TNF]-α, and IL-10） and adherens junctions （E-cadherin, p 120-catenin）, which were ameliorated by glutamine in VILI, both in vitro and in vivo. Methods： For the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table （n = 6 in each group）： control （Group C）; low tidal volume （Group L）; low tidal volume ＋ glutamine （Group L ＋ G）; high tidal volume （Group H）; and high tidal volume ＋ glutamine （Group H ＋ G）. Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 （MLE- 12） cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence. Results： In vivo, compared with Group C, total cell counts （t= -28.182, P 〈 0.01）, the percentage of neutrophils （t = -28.095, P 〈 0.01）, IL-6 （t = -28.296, P 〈 0.01 ）, and TNF-α（t = - 19.812, P 〈 0.01 ） in bronchoalveolar lavage （BAL） fluid, lung injury scores （t = -6.708, P 〈 0.01）, and the wet-to-dry ratio （t = - 15.595, P 〈 0.01 ） were increased in Group H; IL- 10 in BAL fluid （t = 9.093, P 〈 0.01 ） and the expression of E-cadherin （t= 10.044, P 〈 0.01） and p120-catenin （t = 13.218, P 〈 0.01） were decreased in Group H. Compared with Group H, total cell counts （t - 14.844, P 〈 0.01 ）, the percentage of neutrophils （t = 18.077, P 〈 0.0 l ）, IL-6 （t - 18.007, P 〈 0.01 ）, and TNF-α （t =1 0.171, P 〈 0.01 ） in BAL fluid were decreased in Group H ＋ G; IL-10 in BAL fluid （t - -7.531, P 〈 0.01 ） and the expression of E-cadherin （t = - 14.814, P 〈 0.01 ） and p 120-catenin （t = -9.114, P 〈 0.01 ） were increased in Group H ＋ G. In vitro, compared with the nonstretching group, the levels of IL-6 （t = 21.111, P 〈 0.01 ） and TNF-α （t - 15.270, P 〈 0.01 ） were increased in the 20% cyclic stretching group; the levels of IL- 10 （t = 5.450, P 〈 0.01 ） and the expression of E-cadherin （t = 17.736, P 〈 0.01 ） and p 120-catenin （t = 16.136, P 〈 0.01 ） were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 （t = 11.818, P 〈 0.01） and TNF-α （t = 8.631, P 〈 0.01 ） decreased in the glutamine group; the levels of IL- 10 （t = 3.203, P 〈 0.05） and the expression of E-cadherin （t= 13.567, P 〈 0.01） and p 120-catenin （t = -10.013, P 〈 0.01） were increased in the glutamine group. Conclusions： High tidal volume mechanical ventilation and 20% cyclic stretching could cause VIM. Glutamine regulates VIM by improving cytokines and increasing the adherens junctions, protein E-cadherin and p 120-catenin, to enhance the epithelial barrier function.展开更多
Background Nitric oxide （NO） plays an important role in acute lung injury （ALl）, acute respiratory distress syndrome （ARDS）, and in ventilator-induced lung injury （VILI）. A change in the balance of endothelin...Background Nitric oxide （NO） plays an important role in acute lung injury （ALl）, acute respiratory distress syndrome （ARDS）, and in ventilator-induced lung injury （VILI）. A change in the balance of endothelin-1 （ET-1） and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model. Methods Models of oleic acid induced ALl were established in dogs; these models were then randomized into three groups undergone different tidal volume （VT） mechanical ventilation, which included a VT6 group （VT equaled to 6 ml/kg body weight, positive end expiratory pressure （PEEP） equaled to 10 cmH20, n=-6）, a VT10 group （VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH20, n=-4） and a VT20 group （VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH20, n=-6） for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial. Results PaO2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALl models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation （P 〈0.05） while the serum NO levels were similar in the three groups （all P 〉0.05）. There was no significant difference in serum ratio of ET-1/NO between any two out of three groups （P 〉0.05）, although there was a significant positive relationship between serum ET-1 and serum NO （r=0.80, P 〈0.01）. The levels of ET-1 and NO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that in the VT6 group and VT10 group （both P 〈0.05） while there was no significant difference in lung NO levels between two groups （P〉0.05）. In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation （P 〈0.05） as there was a significant positive relationship between ET-1 and NO in the lung （r=0.54, P 〈0.05）. Conclusions The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1 levels increased much more than the NO levels in the lung, though there was a significant positive relationship between levels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model and changing the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.展开更多
Background： Subsequent neutrophil （polymorphonuclear neutrophil [PMN]）-predominant inflammatory response is a predominant feature of ventilator-induced lung injury （VILI）, and mesenchymal stem cell （MSC） can im...Background： Subsequent neutrophil （polymorphonuclear neutrophil [PMN]）-predominant inflammatory response is a predominant feature of ventilator-induced lung injury （VILI）, and mesenchymal stem cell （MSC） can improve mice survival model of endotoxin-induced acute lung injury, reduce lung impairs, and enhance the repair inflammatory in the VILI is still unknown. This study aimed to inflammatory in the mechanical VILI. of VILI. However, whether MSC could attenuate PMN-predominant test whether MSC intervention could attenuate the PMN-predominate Methods： Sprague-Dawley rats were ventilated for 2 hours with large tidal volume （20 mL/kg）. MSCs were given before or after ventilation. The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation, and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation. Results： Mechanical ventilation （MV） caused significant lung injury reflected by increasing in PMN pulmonary sequestration, inflammatory chemokines （tumor necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein 2） in the bronchoalveolar lavage fluid, and injury score of the lung tissue. These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity, production of radical oxygen series. MSC intervention especially pretreatment attenuated subsequent lung injury, systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation. Conclusions： MV causes profound lung injury and PMN-predominate inflammatory responses. The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.展开更多
The standard treatment for acute respiratory distress syndrome(ARDS) is supportive in the form of low tidal volume ventilation applied after significant lung injury has already developed. Nevertheless, ARDS mortality ...The standard treatment for acute respiratory distress syndrome(ARDS) is supportive in the form of low tidal volume ventilation applied after significant lung injury has already developed. Nevertheless, ARDS mortality remains unacceptably high(> 40%). Indeed, once ARDS is established it becomes refractory to treatment, and therefore avoidance is key. However, preventive techniques and therapeutics to reduce the incidence of ARDS in patients at high-risk have not been validated clinically. This review discusses the current data suggesting that preemptive application of the properly adjusted mechanical breath can block progressive acute lung injury and significantly reduce the occurrence of ARDS.展开更多
目的探讨幼兔机械通气、内毒素及机械通气复合内毒素肺损伤时,肺组织核因子-κB(NF-κB)活化及其对TNF-α和IL-8表达的影响。方法60只普通级幼兔随机等分为对照组(NMV)、大潮气量组(LVMV)、内毒素组(ENMV)和复合损伤组(EMV)(n=15),检测...目的探讨幼兔机械通气、内毒素及机械通气复合内毒素肺损伤时,肺组织核因子-κB(NF-κB)活化及其对TNF-α和IL-8表达的影响。方法60只普通级幼兔随机等分为对照组(NMV)、大潮气量组(LVMV)、内毒素组(ENMV)和复合损伤组(EMV)(n=15),检测各时相肺组织NF-κB活性、IκBα含量、TNF-α和IL-8的基因表达和蛋白含量变化,并观察肺组织病理改变。结果NF-κB活性在NMV较底,ENMV致伤后2 h NF-κB活性达最高,而LVMV通气4 h NF-κB活性达高峰;EMV伤后各时相点NF-κB活性强度显著高于其它两组(P<0.01)。IκBα含量在NMV较高,ENMV致伤后4 h IκBα含量降至最低;出现显著下降的时间早于LVMV;EMV在通气后2、4、6 h的IκBα含量降低程度显著大于其它两组(P<0.01)。TNF-α、IL-8 mRNA和蛋白含量在NMV较低,在ENMV和EMV肺组织伤后TNF-α、IL-8 mRNA和蛋白含量峰值早于LVMV,EMV伤后2、4、6 h TNF-αmRNA表达和蛋白含量显著高于其它两组(P<0.05,P<0.01)。结论机械通气和内毒素可能通过不同的途径使NF-κB活化,启动致炎细胞因子的转录,导致肺损伤。机械通气和内毒素先后作用于机体对NF-κB的活化可能有相互反应后效应的加强,加重肺损伤。展开更多
目的评价甲泼尼龙对呼吸机相关性肺损伤(VILI)大鼠肺组织瞬时受体电位香草酸4 (TRPV4)/基质金属蛋白酶2/9(MMP-2/MMP-9)信号通路的影响。方法清洁级雄性SD大鼠100只,采用随机数字表法分为5组(n=20):对照组(C组)、机械通气组(V组)、甲泼...目的评价甲泼尼龙对呼吸机相关性肺损伤(VILI)大鼠肺组织瞬时受体电位香草酸4 (TRPV4)/基质金属蛋白酶2/9(MMP-2/MMP-9)信号通路的影响。方法清洁级雄性SD大鼠100只,采用随机数字表法分为5组(n=20):对照组(C组)、机械通气组(V组)、甲泼尼龙组(Mp组)、甲泼尼龙+GSK1016790A组(MpG组)、HC-067047组(H组)。C组不行机械通气,自主呼吸空气4 h;V组机械通气(RR 40次/min,VT 40 m L/kg,I∶E 1∶1,PEEP 0,Fi O221%) 4 h;Mp组在机械通气前20 min静脉输注甲泼尼龙10.0 mg/kg;MpG组在给予甲泼尼龙前20 min静脉输注GSK1016790A 0.025 mg/kg;H组机械通气前30 min静脉输注HC-067047 10.0 mg/kg。机械通气4 h时,检测支气管肺泡灌洗液(BALF)中白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)、总蛋白浓度,测定肺通透指数(LPI)、肺湿/干质量比(W/D),观察肺组织病理学结果。Western blot法检测肺组织TRPV4、MMP-2、MMP-9的表达水平。结果与C组比较,V组和MpG组BALF中IL-1(ng/m L:84.56±5.35 vs. 144.85±9.39、121.56±7.69)、TNF-α(ng/m L:179.65±45.73 vs. 486.18±94.79、316.93±69.71)、总蛋白(mg/m L:321.29±28.76 vs. 687.78±65.78、476.39±46.67)升高,肺组织LPI [(2.47±0.17)×10^(-3)vs.(6.19±0.29)×10^(-3)、(4.24±0.25)×10^(-3)]、W/D比值(4.42±0.19 vs. 8.83±0.61、6.32±0.41)升高,TRPV4(1.85±0.25 vs.5.81±0.92、3.87±0.65)、MMP-2 (0.44±0.06 vs. 1.16±0.23、0.85±0.11)、MMP-9(0.19±0.03 vs. 0.46±0.09、0.34±0.07)表达上调(P<0.05);与V组比较,Mp组、MpG组和H组BALF中IL-1(ng/m L:144.85±9.39 vs. 89.78±5.91、121.56±7.69、94.23±6.78)、TNF-α(ng/m L:486.18±94.79 vs. 186.42±49.37、316.93±69.71、193.71±51.41)、总蛋白(mg/m L:687.78±65.78 vs. 348.78±31.52、476.39±46.67、359.68±36.12)降低,肺组织LPI [(6.19±0.29)×10^(-3)vs.(2.85±0.14)×10^(-3)、(4.24±0.25)×10^(-3)、(2.97±0.21)×10^(-3)]、W/D比值(8.83±0.61 vs. 4.75±0.22、6.32±0.41、4.82±0.25)降低,TRPV4(5.81±0.92 vs. 2.13±0.29、3.87±0.65、2.35±0.37)、MMP-2 (1.16±0.23 vs. 0.48±0.08、0.85±0.11、0.52±0.08)、MMP-9(0.46±0.09 vs. 0.22±0.04、0.34±0.07、0.25±0.05)表达下调(P<0.05),肺组织病理损伤减轻;与Mp组比较,MpG组BALF中IL-1 (ng/m L:89.78±5.91 vs. 121.56±7.69)、TNF-α(ng/m L:186.42±49.37 vs. 316.93±69.71)、总蛋白(mg/m L:348.78±31.52 vs. 476.39±46.67)升高,肺组织LPI [(2.85±0.14)×10^(-3)vs.(4.24±0.25)×10^(-3)]、W/D比值(4.75±0.22 vs. 6.32±0.41)升高,TRPV4(2.13±0.29 vs. 3.87±0.65)、MMP-2(0.48±0.08 vs. 0.85±0.11)、MMP-9(0.22±0.04 vs. 0.34±0.07)表达上调(P<0.05)。结论甲泼尼龙可减轻大鼠VILI,与其抑制TRPV4/MMP-2/MMP-9信号通路有关。展开更多
基金supported by a grant from the Natural Science Foundation of Shandong Province of China(No.Y2007C119)
文摘Neutrophils play a critical role in ventilation-induced lung injury. This study was aimed to investigate the characteristics of neutrophils influx in lungs induced by high tidal volume ventilation. Anaesthetized rats were randomly divided into low tidal volume ventilation group (Vt: 7 mL/kg, LV group) or high tidal volume ventilation group (Vt:42mL/kg, HV group ) (n=40 in each). Rats in each group were ventilated for 0, 60, 90, 120 and 240 min. The wet/dry lung weight ratio (W/D) was measured. The levels of macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α), and the activity of myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA). The number of neutrophils in bronchoalveolar lavage fluid (BALF) was counted after Wright’s staining, and the percentage of netrophils in lung tissues calculated. Histopatholgical examination was used to observe the changes of lung tissues after different ventilations. The results showed that the W/D weight ratio was increased, and the levels of MIP-2 and TNF-α significantly enhanced in HV group at 90, 120 and 240 min. Neutrophils in BALF and the neutrophil percentage in lung tissues were also elevated at 120 and 240 min, which coincided with the enhanced activity of MPO in HV group. The lung injury was significantly related with the ventilation time and the infiltration of neutrophils in lungs in HV group. In conclusion, in ventilation-induced lung injury, neutrophil infiltration is present in a time-dependent manner and associated with the aggravated lung injury. Pulmonary structural damage may be the main reason for ventilation-induced lung injury.
文摘Expiratory flow limitation(EFL), that is the inability of expiratory flow to increase in spite of an increase of the driving pressure, is a common and unrecognized occurrence during mechanical ventilation in a variety of intensive care unit conditions. Recent evidence suggests that the presence of EFL is associated with an increase in mortality, at least in acute respiratory distress syndrome(ARDS) patients, and in pulmonary complications in patients undergoing surgery. EFL is a major cause of intrinsic positive end-expiratory pressure(PEEPi), which in ARDS patients is heterogeneously distributed, with a consequent increase of ventilation/perfusion mismatch and reduction of arterial oxygenation. Airway collapse is frequently concomitant to the presence of EFL.When airways close and reopen during tidal ventilation, abnormally high stresses are generated that can damage the bronchiolar epithelium and uncouple small airways from the alveolar septa, possibly generating the small airways abnormalities detected at autopsy in ARDS. Finally, the high stresses and airway distortion generated downstream the choke points may contribute to parenchymal injury, but this possibility is still unproven. PEEP application can abolish EFL, decrease PEEPi heterogeneity, and limit recruitment/derecruitment.Whether increasing PEEP up to EFL disappearance is a useful criterion for PEEP titration can only be determined by future studies.
基金Acknowledgements This study was supported by the National Natural Science Foundation of China （Grant No.30772085） and graduate innovation fund of Heilongjiang Province.
基金supported by grants from the Shanghai Health Bureau issues(2007102)
文摘BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries （VILI） and to explore its potential mechanisms.METHODS： Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope.RESULTS： IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-a ray degree of group B was significantly higher than that in the other groups （P〈0.01）, especially in group C （P〉0.05）. The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B.CONCLUSION： Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.
文摘Driving pressure(ΔP)is a core therapeutic component of mechanical ventilation(MV).Varying levels ofΔP have been employed during MV depending on the type of underlying pathology and severity of injury.However,ΔP levels have also been shown to closely impact hard endpoints such as mortality.Considering this,conducting an in-depth review ofΔP as a unique,outcome-impacting therapeutic modality is extremely important.There is a need to understand the subtleties involved in making sureΔP levels are optimized to enhance outcomes and minimize harm.We performed this narrative review to further explore the various uses ofΔP,the different parameters that can affect its use,and how outcomes vary in different patient populations at different pressure levels.To better utilizeΔP in MV-requiring patients,additional large-scale clinical studies are needed.
文摘Independent lung ventilation,though infrequently used in the critical care setting,has been reported as a rescue strategy for patients in respiratory failure resulting from severe unilateral lung pathology.This involves isolating and ventilating the right and left lung differently,using separate ventilators.Here,we describe our experience with independent lung ventilation in a patient with unilateral diffuse alveolar hemorrhage,who presented with severe hypoxemic respiratory failure despite maximal ventilatory support.Conventional ventilation in this scenario leads to preferential distribution of tidal volume to the nondiseased lung causing over distension and inadvertent volume trauma.Since each lung has a different compliance and respiratory mechanics,instituting separate ventilation strategies to each lung could potentially minimize lung injury.Based on review of literature,we provide a detailed description of indications and procedures for establishing independent lung ventilation,and also provide an algorithm for management and weaning a patient from independent lung ventilation.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81372036, No. 81671890, No. 81601669, and No. 81500064）.
文摘Objective：Mechanical ventilation （MV） has long been used as a life-sustaining approach for several decades.However,researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly,which is termed as ventilator-induced lung injury （VILI）.This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms.Data Sources：This review was based on articles in the PubMed database up to December 2017 using the following keywords：＂ventilator-induced lung injury＂,＂pathogenesis＂,＂mechanism＂,and ＂biotrauma＂.Study Selection：Original articles and reviews pertaining to mechanisms of VILI were included and reviewed.Results：The pathogenesis of VILI was defined gradually,from traditional pathological mechanisms （barotrauma,volutrauma,and atelectrauma） to biotrauma.High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas,volutrauma,and atelectrauma.In the past two decades,accumulating evidence have addressed the importance of biotrauma during VILI,the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release,reactive oxygen species production,complement activation as well as mechanotransduction.Conclusions：Barotrauma,volutrauma,atelectrauma,and biotrauma contribute to VILI,and the molecular mechanisms are being clarified gradually.More studies are warranted to figure out how to minimize lung injury induced by MV.
基金This work was supported by grants from the National Natural Science Foundation of China （Nos. 81570074, 81770076）.
文摘Background： Ventilator-induced lung injury （VILI） is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated, This study examined the relationship between inflammatory cytokines （interleukin JILl-6, tumor necrosis factor [TNF]-α, and IL-10） and adherens junctions （E-cadherin, p 120-catenin）, which were ameliorated by glutamine in VILI, both in vitro and in vivo. Methods： For the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table （n = 6 in each group）： control （Group C）; low tidal volume （Group L）; low tidal volume ＋ glutamine （Group L ＋ G）; high tidal volume （Group H）; and high tidal volume ＋ glutamine （Group H ＋ G）. Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 （MLE- 12） cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence. Results： In vivo, compared with Group C, total cell counts （t= -28.182, P 〈 0.01）, the percentage of neutrophils （t = -28.095, P 〈 0.01）, IL-6 （t = -28.296, P 〈 0.01 ）, and TNF-α（t = - 19.812, P 〈 0.01 ） in bronchoalveolar lavage （BAL） fluid, lung injury scores （t = -6.708, P 〈 0.01）, and the wet-to-dry ratio （t = - 15.595, P 〈 0.01 ） were increased in Group H; IL- 10 in BAL fluid （t = 9.093, P 〈 0.01 ） and the expression of E-cadherin （t= 10.044, P 〈 0.01） and p120-catenin （t = 13.218, P 〈 0.01） were decreased in Group H. Compared with Group H, total cell counts （t - 14.844, P 〈 0.01 ）, the percentage of neutrophils （t = 18.077, P 〈 0.0 l ）, IL-6 （t - 18.007, P 〈 0.01 ）, and TNF-α （t =1 0.171, P 〈 0.01 ） in BAL fluid were decreased in Group H ＋ G; IL-10 in BAL fluid （t - -7.531, P 〈 0.01 ） and the expression of E-cadherin （t = - 14.814, P 〈 0.01 ） and p 120-catenin （t = -9.114, P 〈 0.01 ） were increased in Group H ＋ G. In vitro, compared with the nonstretching group, the levels of IL-6 （t = 21.111, P 〈 0.01 ） and TNF-α （t - 15.270, P 〈 0.01 ） were increased in the 20% cyclic stretching group; the levels of IL- 10 （t = 5.450, P 〈 0.01 ） and the expression of E-cadherin （t = 17.736, P 〈 0.01 ） and p 120-catenin （t = 16.136, P 〈 0.01 ） were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 （t = 11.818, P 〈 0.01） and TNF-α （t = 8.631, P 〈 0.01 ） decreased in the glutamine group; the levels of IL- 10 （t = 3.203, P 〈 0.05） and the expression of E-cadherin （t= 13.567, P 〈 0.01） and p 120-catenin （t = -10.013, P 〈 0.01） were increased in the glutamine group. Conclusions： High tidal volume mechanical ventilation and 20% cyclic stretching could cause VIM. Glutamine regulates VIM by improving cytokines and increasing the adherens junctions, protein E-cadherin and p 120-catenin, to enhance the epithelial barrier function.
文摘Background Nitric oxide （NO） plays an important role in acute lung injury （ALl）, acute respiratory distress syndrome （ARDS）, and in ventilator-induced lung injury （VILI）. A change in the balance of endothelin-1 （ET-1） and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model. Methods Models of oleic acid induced ALl were established in dogs; these models were then randomized into three groups undergone different tidal volume （VT） mechanical ventilation, which included a VT6 group （VT equaled to 6 ml/kg body weight, positive end expiratory pressure （PEEP） equaled to 10 cmH20, n=-6）, a VT10 group （VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH20, n=-4） and a VT20 group （VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH20, n=-6） for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial. Results PaO2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALl models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation （P 〈0.05） while the serum NO levels were similar in the three groups （all P 〉0.05）. There was no significant difference in serum ratio of ET-1/NO between any two out of three groups （P 〉0.05）, although there was a significant positive relationship between serum ET-1 and serum NO （r=0.80, P 〈0.01）. The levels of ET-1 and NO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that in the VT6 group and VT10 group （both P 〈0.05） while there was no significant difference in lung NO levels between two groups （P〉0.05）. In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation （P 〈0.05） as there was a significant positive relationship between ET-1 and NO in the lung （r=0.54, P 〈0.05）. Conclusions The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1 levels increased much more than the NO levels in the lung, though there was a significant positive relationship between levels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model and changing the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.
基金This study was supported by a grant from Natural Science Foundation of Guangdong Province （No. S2012040006274）.
文摘Background： Subsequent neutrophil （polymorphonuclear neutrophil [PMN]）-predominant inflammatory response is a predominant feature of ventilator-induced lung injury （VILI）, and mesenchymal stem cell （MSC） can improve mice survival model of endotoxin-induced acute lung injury, reduce lung impairs, and enhance the repair inflammatory in the VILI is still unknown. This study aimed to inflammatory in the mechanical VILI. of VILI. However, whether MSC could attenuate PMN-predominant test whether MSC intervention could attenuate the PMN-predominate Methods： Sprague-Dawley rats were ventilated for 2 hours with large tidal volume （20 mL/kg）. MSCs were given before or after ventilation. The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation, and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation. Results： Mechanical ventilation （MV） caused significant lung injury reflected by increasing in PMN pulmonary sequestration, inflammatory chemokines （tumor necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein 2） in the bronchoalveolar lavage fluid, and injury score of the lung tissue. These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity, production of radical oxygen series. MSC intervention especially pretreatment attenuated subsequent lung injury, systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation. Conclusions： MV causes profound lung injury and PMN-predominate inflammatory responses. The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.
文摘The standard treatment for acute respiratory distress syndrome(ARDS) is supportive in the form of low tidal volume ventilation applied after significant lung injury has already developed. Nevertheless, ARDS mortality remains unacceptably high(> 40%). Indeed, once ARDS is established it becomes refractory to treatment, and therefore avoidance is key. However, preventive techniques and therapeutics to reduce the incidence of ARDS in patients at high-risk have not been validated clinically. This review discusses the current data suggesting that preemptive application of the properly adjusted mechanical breath can block progressive acute lung injury and significantly reduce the occurrence of ARDS.
文摘目的探讨幼兔机械通气、内毒素及机械通气复合内毒素肺损伤时,肺组织核因子-κB(NF-κB)活化及其对TNF-α和IL-8表达的影响。方法60只普通级幼兔随机等分为对照组(NMV)、大潮气量组(LVMV)、内毒素组(ENMV)和复合损伤组(EMV)(n=15),检测各时相肺组织NF-κB活性、IκBα含量、TNF-α和IL-8的基因表达和蛋白含量变化,并观察肺组织病理改变。结果NF-κB活性在NMV较底,ENMV致伤后2 h NF-κB活性达最高,而LVMV通气4 h NF-κB活性达高峰;EMV伤后各时相点NF-κB活性强度显著高于其它两组(P<0.01)。IκBα含量在NMV较高,ENMV致伤后4 h IκBα含量降至最低;出现显著下降的时间早于LVMV;EMV在通气后2、4、6 h的IκBα含量降低程度显著大于其它两组(P<0.01)。TNF-α、IL-8 mRNA和蛋白含量在NMV较低,在ENMV和EMV肺组织伤后TNF-α、IL-8 mRNA和蛋白含量峰值早于LVMV,EMV伤后2、4、6 h TNF-αmRNA表达和蛋白含量显著高于其它两组(P<0.05,P<0.01)。结论机械通气和内毒素可能通过不同的途径使NF-κB活化,启动致炎细胞因子的转录,导致肺损伤。机械通气和内毒素先后作用于机体对NF-κB的活化可能有相互反应后效应的加强,加重肺损伤。
文摘目的评价甲泼尼龙对呼吸机相关性肺损伤(VILI)大鼠肺组织瞬时受体电位香草酸4 (TRPV4)/基质金属蛋白酶2/9(MMP-2/MMP-9)信号通路的影响。方法清洁级雄性SD大鼠100只,采用随机数字表法分为5组(n=20):对照组(C组)、机械通气组(V组)、甲泼尼龙组(Mp组)、甲泼尼龙+GSK1016790A组(MpG组)、HC-067047组(H组)。C组不行机械通气,自主呼吸空气4 h;V组机械通气(RR 40次/min,VT 40 m L/kg,I∶E 1∶1,PEEP 0,Fi O221%) 4 h;Mp组在机械通气前20 min静脉输注甲泼尼龙10.0 mg/kg;MpG组在给予甲泼尼龙前20 min静脉输注GSK1016790A 0.025 mg/kg;H组机械通气前30 min静脉输注HC-067047 10.0 mg/kg。机械通气4 h时,检测支气管肺泡灌洗液(BALF)中白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)、总蛋白浓度,测定肺通透指数(LPI)、肺湿/干质量比(W/D),观察肺组织病理学结果。Western blot法检测肺组织TRPV4、MMP-2、MMP-9的表达水平。结果与C组比较,V组和MpG组BALF中IL-1(ng/m L:84.56±5.35 vs. 144.85±9.39、121.56±7.69)、TNF-α(ng/m L:179.65±45.73 vs. 486.18±94.79、316.93±69.71)、总蛋白(mg/m L:321.29±28.76 vs. 687.78±65.78、476.39±46.67)升高,肺组织LPI [(2.47±0.17)×10^(-3)vs.(6.19±0.29)×10^(-3)、(4.24±0.25)×10^(-3)]、W/D比值(4.42±0.19 vs. 8.83±0.61、6.32±0.41)升高,TRPV4(1.85±0.25 vs.5.81±0.92、3.87±0.65)、MMP-2 (0.44±0.06 vs. 1.16±0.23、0.85±0.11)、MMP-9(0.19±0.03 vs. 0.46±0.09、0.34±0.07)表达上调(P<0.05);与V组比较,Mp组、MpG组和H组BALF中IL-1(ng/m L:144.85±9.39 vs. 89.78±5.91、121.56±7.69、94.23±6.78)、TNF-α(ng/m L:486.18±94.79 vs. 186.42±49.37、316.93±69.71、193.71±51.41)、总蛋白(mg/m L:687.78±65.78 vs. 348.78±31.52、476.39±46.67、359.68±36.12)降低,肺组织LPI [(6.19±0.29)×10^(-3)vs.(2.85±0.14)×10^(-3)、(4.24±0.25)×10^(-3)、(2.97±0.21)×10^(-3)]、W/D比值(8.83±0.61 vs. 4.75±0.22、6.32±0.41、4.82±0.25)降低,TRPV4(5.81±0.92 vs. 2.13±0.29、3.87±0.65、2.35±0.37)、MMP-2 (1.16±0.23 vs. 0.48±0.08、0.85±0.11、0.52±0.08)、MMP-9(0.46±0.09 vs. 0.22±0.04、0.34±0.07、0.25±0.05)表达下调(P<0.05),肺组织病理损伤减轻;与Mp组比较,MpG组BALF中IL-1 (ng/m L:89.78±5.91 vs. 121.56±7.69)、TNF-α(ng/m L:186.42±49.37 vs. 316.93±69.71)、总蛋白(mg/m L:348.78±31.52 vs. 476.39±46.67)升高,肺组织LPI [(2.85±0.14)×10^(-3)vs.(4.24±0.25)×10^(-3)]、W/D比值(4.75±0.22 vs. 6.32±0.41)升高,TRPV4(2.13±0.29 vs. 3.87±0.65)、MMP-2(0.48±0.08 vs. 0.85±0.11)、MMP-9(0.22±0.04 vs. 0.34±0.07)表达上调(P<0.05)。结论甲泼尼龙可减轻大鼠VILI,与其抑制TRPV4/MMP-2/MMP-9信号通路有关。
