High VT Group Research Articles

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome

ObjectiveEvidence only proves low surpasses high tidal volume (VT) for acute respiratory distress syndrome (ARDS). Intermediate VT is a common setting for ARDS patients and has been demonstrated as effective as low VT in non-ARDS patients. The effectiveness of intermediate VT in ARDS has not been studied and is the objective of this study. DesignA retrospective cohort study. SettingFive ICUs with their totally 130 beds in Taiwan. Patients or participantsARDS patients under invasive ventilation. InterventionsNo. Main variables of interest28-D mortality. ResultTotally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean VT=6.7ml/kg), intermediate (mean VT=8.9ml/kg) and high (mean VT=11.2ml/kg) VT groups. With similar baseline ARDS and ICU severities, intermediate and low VT groups did not differ in 28-D mortality (47% vs. 63%, P=0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high VT was independently associated with 28-D and 90-D mortality, but intermediate VT was not significantly associated with 28-D mortality (HR 1.34, CI 0.92–1.97, P=0.13) or 90-D mortality. When the intermediate and low VT groups were matched in propensity scores (n=66 for each group), their outcomes were also not significantly different. ConclusionIntermediate VT, with its outcomes similar to small VT, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials.

Role of Mitophagy-based TLR9 Signal Pathway in Neonatal Ventilator-induced Lung Injury

The study focused on the role of mitophagy in neonatal ventilator-induced lung injury (VILI). Immunoassays were used to study the TLR9 signaling pathway of neonatal VILI, expected to provide a feasible solution for neonatal VILI. The mice were randomly divided into four groups, group A: spontaneous breathing group; group B: normal tidal volume (VT) group (VT=9mL/kg); group C: high VT group (VT=39mL/kg); and group D: ODN2088 (400μg/ Only) intervention + high VT group. The four groups were compared for the expression of inflammatory factors. It was found that as the culture time increased, the expression of TLR9, MyD88, and NF-κBp65 in the lung tissue of the large VT group was significantly higher than those in the spontaneous breathing group and normal VT group, and the differences were statistically significant; and TLR9 inhibitors could activate the TLR9-MyD88 signaling pathway to up-regulate the expression of NF-κB, mediating the release of inflammatory factors to cause VILI.

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome.

ObjectiveEvidence only proves low surpasses high tidal volume (VT) for acute respiratory distress syndrome (ARDS). Intermediate VT is a common setting for ARDS patients and has been demonstrated as effective as low VT in non-ARDS patients. The effectiveness of intermediate VT in ARDS has not been studied and is the objective of this study.DesignA retrospective cohort study.SettingFive ICUs with their totally 130 beds in Taiwan.Patients or participantsARDS patients under invasive ventilation.InterventionsNo.Main variables of interest28-D mortality.ResultTotally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean VT = 6.7 ml/kg), intermediate (mean VT = 8.9 ml/kg) and high (mean VT = 11.2 ml/kg) VT groups. With similar baseline ARDS and ICU severities, intermediate and low VT groups did not differ in 28-D mortality (47% vs. 63%, P = 0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high VT was independently associated with 28-D and 90-D mortality, but intermediate VT was not significantly associated with 28-D mortality (HR 1.34, CI 0.92–1.97, P = 0.13) or 90-D mortality. When the intermediate and low VT groups were matched in propensity scores (n = 66 for each group), their outcomes were also not significantly different.ConclusionIntermediate VT, with its outcomes similar to small VT, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials.

A Study of Inflammatory Response and Lung Injury Induced by Variable Tidal Volumes in Mechanically Ventilated Children

Background We aimed to compare the effects of high tidal volume (Vt) versus low Vt mechanical ventilation (MV) on systemic interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF- α) cytokines production and induction of lung injury in mechanically ventilated children. Materials and Methods: Thisprospectiveobservational study was performed on 60 critically ill mechanically ventilated children from 2018 to 2019, at PICU of South Valley University and Minia University hospitals, Qena and Minia cities, Egypt. After application of the inclusion and exclusion criteria, we compared MV with high Vt of 9-11 ml (group I) versus low Vt of 5-7ml (group II) per kilogram of predicted body weight in critically ill children. Plasma levels of IL8 and TNF- α cytokines were estimated at the onset of MV and after 24 hours in both groups. Lung injury development was evidenced by change in oxygenation parameters. Results: Sixty patients on MV (30 with high Vt versus 30 with lower Vt) were enrolled in the study. Plasma levels of interleukin-8 and TNF- α were increased in both groups 24 hours after initiation of MV, but this rise was significantly higher in high Vt group (p <0.05). There were significant positive correlations between tidal volume and oxygenation index (p-value <0.05, r=0.32), and with plasma IL-8 (r=0.34, p= 0.01), while negative correlation between tidal volume and change in PaO2/fiO2 ratio after 24 hours MV (r= -0.34, p <0.05). Conclusion Mechanical ventilation with high Vt was associated with increased IL-8, and TNF- α cytokines production, and will induce lung injury as evidenced by acute hypoxemia and deterioration in oxygenation parameters (PaO2/FiO2 ratio less than 300 mmHg).

Effects of mechanical ventilation with different tidal volumes on right ventricular hemodynamics in acute respiratory distress syndrome rats

To explore the effect of different tidal volumes (VT) on the hemodynamics of right heart in acute respiratory distress syndrome (ARDS) rats induced by oleic acid (OA). Sixty adult male Sprague-Dawley (SD) rats were divided into control group (n = 20), ARDS model group (n = 20), low VT (LVT) group (n = 10) and high VT (HVT) group (n = 10) by random number table. ARDS model was reproduced by injecting OA 0.15 mL/kg through a jugular vein. The control group was given the same amount of normal saline. The success of modeling was judged by the oxygenation index (PaO2/FiO2) 2 hours after modeling, at the same time, the lung tissues were collected, the wet/dry weight (W/D) ratio was determined, and the lung histopathological changes were measured by lung injury score. The rats in the LVT group and HVT group were given mechanical ventilation with VT of 6 mL/kg or 20 mL/kg for 4 hours, respectively at 2 hours after modeling. The rats in the control group and the ARDS model group maintained spontaneous breathing. After mechanical ventilation for 4 hours, the heart rate (HR), right ventricular systolic pressure (RVSP), the maximum rate of rising of right ventricular pressure (dp/dt max), and the blood pressure (BP) were measured. Meanwhile, arterial blood samples were collected for blood gas analysis, including pH value, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) and PaO2/FiO2. The rats in the ARDS model group showed symptoms of respiratory distress 1 hour after modeling, and the lung tissue samples showed obvious patchy bleeding 2 hours after modeling, while the control group showed no such changes. The PaO2/FiO2 in the ARDS model group was significantly lower than that in the control group [mmHg (1 mmHg = 0.133 kPa): 294.3±5.9 vs. 459.0±4.4, P < 0.01], and the lung W/D ratio and lung injury score were significantly higher (lung W/D ratio: 8.24±0.25 vs. 4.48±0.13, lung injury score: 0.60±0.03 vs. 0.12±0.02, both P < 0.01). It indicated that ARDS model was successfully reproduced. The arterial blood gas analysis and hemodynamic parameters of the ARDS model group were significantly worse than those of the control group. After 4-hour mechanical ventilation, the blood gas parameters of the LVT group were better than those of the ARDS model group and the HVT group [pH value: 7.36±0.02 vs. 7.24±0.02, 7.13±0.01; PaO2 (mmHg): 92.4±2.1 vs. 61.8±2.3, 76.6±2.2; PaCO2 (mmHg): 49.6±1.7 vs. 61.8±1.8, 33.6±1.3; PaO2/FiO2 (mmHg): 440.0±10.2 vs. 274.3±21.4, 364.7±10.5; all P < 0.05]. HR, BP and dp/dt max in the LVT group were significantly higher than those in the ARDS model group and the HVT group [HR (bpm): 346.9±5.4 vs. 302.3±10.1, 265.5±12.2; BP (mmHg): 125.4±2.2 vs. 110.0±2.5, 89.2±2.8; dp/dt max (mmHg/s): 1 393.3±30.3 vs. 1 236.4±20.5, 896.1±19.5; all P < 0.05], and RVSP was significantly lower than that in the ARDS model group and the HVT group (mmHg: 31.3±0.4 vs. 34.0±1.0, 38.8±0.9, both P < 0.05). Mechanical ventilation with low VT can improve the hemodynamic parameters of the right ventricle and protect the function of the right heart in ARDS rats.

Role and mechanism of Ly6Chigh monocyte in ventilator-induced lung injury in mice

To investigate the role and mechanism of Ly6Chigh monocyte in mice with ventilator-induced lung injury (VILI). Forty-eight healthy male SPF C57BL/6 mice were divided into spontaneous breathing group (n = 8), normal tidal volume (VT) group (VT was 8 mL/kg, n = 8), and high VT group (VT was 20 mL/kg, n = 32). The mice in the high VT group were subdivided into 1, 2, 3 and 4 hours subgroups, with 8 mice in each subgroup. All mice underwent direct tracheal intubation, those in the spontaneous breathing group maintained spontaneous breathing, and those in the normal VT group and high VT group were mechanically ventilated with different VT. After ventilation for 4 hours, bronchoalveolar lavage fluid (BALF) was collected to determine total protein, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme-linked immune sorbent assay (ELISA). The lung tissues were harvested to determine the wet/dry (W/D) ratio, and lung tissue injury was assessed in terms of lung histopathologic examination after hematoxylin-eosin (HE) staining under the light microscope. The protein expressions of monocyte chemotactic protein-1 (MCP-1) and CC-chemokine receptor 2 (CCR2) in lung tissues were determined by Western Blot. Flow cytometry was used to detect the proportion of Ly6Chigh monocyte in lung tissue. The histopathology of lung tissue structures was normal in the spontaneous breathing group and the normal VT group. Inflammatory reaction began to appear at 2 hours of high VT ventilation, and inflammatory reaction was gradually aggravated with the time extension. Compared with the spontaneous breathing group, the total protein, TNF-α, and IL-1β levels in BALF, the lung W/D ratio and MCP-1 expression were increased from 2 hours of high VT ventilation [total protein in BALF (g/L): 1.05±0.13 vs. 0.58±0.11, TNF-α in BALF (ng/L): 116.86±16.14 vs. 38.27±8.00, IL-1β in BALF (ng/L): 178.98±10.41 vs. 117.56±23.40, lung W/D ratio: 5.76±0.27 vs. 4.98±0.39, MCP-1/GAPDH: 0.87±0.19 vs. 0.29±0.12, all P < 0.05], and CCR2 expression and the proportion of Ly6Chigh monocyte was significantly increased from 3 hours of high VT ventilation [CCR2/GAPDH: 0.84±0.19 vs. 0.24±0.11, Ly6Chigh monocyte proportion: (9.01±2.47)% vs. (1.06±0.35)%, both P < 0.05], and they all showed an increased tendency with the time extension. There was no significant difference in the parameters mentioned above among the spontaneous breathing group, normal VT group and high VT ventilation 1-hour group. Ly6Chigh monocytes are involved in VILI, which aggravate VILI by activating the MCP-1/CCR2 axis.

Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room

Background and objectivesDelivery of inadvertent high tidal volume (VT) during positive pressure ventilation (PPV) in the delivery room is common. High VT delivery during PPV has been associated with haemodynamic...

Role and mechanism of mitochondrial DNA mediated Toll-like receptor 9-myeloid differentiation factor 88 signaling pathway activation in rats with ventilator-induced lung injury

To investigate the role and mechanism of mitochondrial DNA (mtDNA) in rats with ventilator-induced lung injury (VILI) via Toll-like receptor 9 (TLR9)-myeloid differentiation factor 88 (MyD88) signaling pathway. Thirty adult male Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 10): spontaneous breathing group, normal tidal volume (VT) group (NVT group, VT = 8 mL/kg), and high VT group (HVT group, VT = 40 mL/kg). Rats in the NVT group and HVT group were ventilated mechanically with a positive end-expiratory pressure (PEEP) of 0 and the fraction of inspired oxygen (FiO2) at 0.50. After 4 hours of ventilation, the blood from the rats' hearts was collected and the rats were sacrificed, the levels of interleukins (IL-6, IL-1β) and tumor necrosis factor-α (TNF-α) in serum were determined with enzyme-linked immune sorbent assay (ELISA). The bronchoalveolar lavage fluid (BALF) was collected for a determination of total protein by using the bicinchoninic acid (BCA) assay. The lung tissues were harvested to determine the wet/dry (W/D) ratio. The changes in pathobiology of lung tissue were observed with hematoxylin and eosin (HE) staining. The protein expression levels of mtDNA-encoded cytochrome C oxidase subunit IV (COX-IV), TLR9, MyD88 and nuclear factor-κB p65 (NF-κB p65) in lung tissues were determined by immunohistochemistry. The histopathology of lung tissues indicated that lungs from animals ventilated with HVT developed marked lung inflammation changes, whereas no major histological change was observed in animals ventilated with NVT or spontaneously breathing. The pathological score in HVT group was significantly higher than that of spontaneous breathing group and NVT group (3.50±0.41 vs. 0.25±0.09, 0.33±0.10, both P < 0.05). Compared with spontaneous breathing group and NVT group, the ratio of W/D in the HVT group was significantly increased (6.42±0.41 vs. 4.14±0.04, 4.28±0.11, both P < 0.05), the contents of total proteins in BALF were significantly increased (g/L: 0.43±0.04 vs. 0.13±0.01, 0.14±0.01, both P < 0.05), and serum IL-6, IL-1β and TNF-α levels were also increased [IL-6 (μg/L): 1.15±0.17 vs. 0.42±0.10, 0.46±0.04; IL-1β (μg/L): 6.73±0.38 vs. 2.08±0.90, 2.19±0.18; TNF-α (μg/L): 4.10±0.11 vs. 1.12±0.10, 1.14±0.04; all P < 0.05]. Immunohistochemistry results demonstrated that the proteins of COX-IV, TLR9, MyD88 and NF-κB p65 in HVT group were shown in brown, which meant strongly expressed. However, these proteins in spontaneous breathing group and NVT group were uncolored or shown in buff, which meant unexpressed or weakly expressed. The results of quantitative analysis indicated that the immunoreactive scores (IRS) of COX-IV, TLR9, MyD88 and NF-κB p65 in HVT group were significantly higher than those in spontaneous breathing group and NVT group (COX-IV IRS: 8.80±2.17 vs. 0.80±0.45, 1.40±0.55; TLR9 IRS: 8.40±2.51 vs. 1.00±0.71, 1.20±0.84; MyD88 IRS: 9.40±1.52 vs. 1.40±0.55, 1.60±0.55; NF-κB p65 IRS: 9.80±2.05 vs. 1.00±0.71, 1.20±0.84; all P < 0.05). There was no significant difference in all of the parameters between spontaneous breathing group and NVT group (all P > 0.05). mtDNA contributes significantly to VILI by activating the TLR9-MyD88 signaling pathway, resulting in subsequent secretion of NF-κB p65 and the proinflammatory cytokines, which induce acute inflammatory injury of lung tissue.

Relationship between shedding of syndecan-4 in lung tissues and ventilator-induced lung injury in rats

Objective To evaluate the relationship between the shedding of syndecan-4 (SDC-4) in lung tissues and ventilator-induced lung injury in rats. Methods Thirty pathogen-free healthy adult male Wistar rats, weighing 220-250 g, were divided into 3 groups (n=10 each) using a random number table: control group (group C), mechanical ventilation with traditional tidal volume (VT) group (group T-VT) and mechanical ventilation with high VT group (group H-VT). The animals were anesthetized with pentobarbital sodium and tracheostomized.The rats kept spontaneous breathing in group C. The rats were mechanically ventilated for 4 h with the VT set at 6 ml/kg in group T-VT and with the VT set at 40 ml/kg in group H-VT.Blood samples were collected immediately after the end of ventilation for measurement of serum SDC-4 concentrations by enzyme-linked immunosorbent assay.The left lung was lavaged, and broncho-alveolar lavage fluid was collected for determination of interleukin-1beta (IL-1β), IL-18, tumor necrosis factor-alpha and SDC-4 concentrations by enzyme-linked immunosorbent assay.The lungs were removed for determination of the wet to dry weight ratio and expression of SDC-4 protein and mRNA in lung tissues (by Western blot and real-time polymerase chain reaction, respectively) and for examination of the pathological changes.The lung injury scores were recorded. Results Compared with group C, the wet to dry weight ratio, lung injury scores, concentrations of IL-1β, IL-18, tumor necrosis factor-alpha and SDC-4 in broncho-alveolar lavage fluid and concentrations of SDC-4 in serum were significantly increased, the expression of SDC-4 mRNA was up-regulated, and the expression of SDC-4 was down-regulated in group H-VT (P 0.05). Marked pathological changes of lung tissues were found in group H-VT. Conclusion A large shedding of SDC-4 in lung tissues may be involved in the pathophysiological mechanism of ventilatior-induced lung injury in rats. Key words: Syndecan-4; Respiration, artificial; Respiratory distress syndrome, adult

Study on Rac1/MAPK/ERK pathway mediated mechanism and role in rats with ventilator induced lung injury

To investigate the role of Ras-related C3 botulinum toxin substrate 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (Rac1/MAPK/ERK) signal pathway in rats with ventilator induced lung injury (VILI) and its mechanism. Thirty Sprague-Dawley (SD) rats were randomly divided into spontaneous respiration group, normal tidal volume (VT) group and high VT group with 10 rats in each group. The rats in spontaneous respiration group were kept their spontaneous breathing. The rats in normal VT group and high VT group were performed tracheal intubation after tracheostomy, and underwent mechanical ventilation on bilateral lungs with 6 mL/kg and 40 mL/kg VT respectively with maintenance anesthesia. After 4-hour ventilation, heart blood, bronchoalveolar lavage fluid (BALF) and lung tissues were harvested. The levels of interleukins (IL-1β, IL-6), tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) and macrophage inflammatory protein-2 (MIP-2) in serum and BALF were determined by enzyme linked immunosorbent assay (ELISA). Lung wet/dry radio (W/D) was determined. The lung tissues were stained with hematoxylin and eosin (HE), and pathological changes were observed, and pathological scores were evaluated. The ultra structure changes in type II alveolar epithelial cells (AEC II) were observed with transmission electron microscope. The positive expressions of phosphorylation of extracellular signal-regulated kinase (p-ERK) were determined by immunohistochemistry, and those of Rac1 and F-actin were determined by immunofluorescence. The mRNA expressions of ERK and Rac1 were determined by real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-qPCR), and protein expressions of Rac-1, p-ERK and F-actin were determined by Western Blot. (1) Compared with spontaneous breathing group, lung W/D in both mechanical ventilation groups was significantly increased, with more significant increase in the high VT group (6.64±0.88 vs. 1.79±0.36, P < 0.01). (2) There was no obvious pathological changes in the lung tissue and AEC II of the spontaneously breathing group. In the normal VT group, there was slight edema and infiltration of inflammatory cells; AEC II had less lamellar bodies and uniform distribution of the villi of the alveolar epithelium. In the high VT group, the edema of the lung tissue, the widening of the pulmonary septum, the alveolus congestion, the infiltration of inflammatory cells, and alveolar structure disorder were found; and AEC II was irregular, the number of lamellar bodies in the plastids was decreased and was unevenly distributed. The pulmonary histopathological score in the high VT group was significantly higher than that in the spontaneous breathing group and the normal VT group (12.00±2.00 vs. 6.00±1.51, 8.50±0.53, both P < 0.01). (3) Compared with spontaneous breathing group, IL-1β, IL-6, TNF-α, MPO, and MIP-2 in serum and BALF in both mechanical ventilation groups were significantly increased, with more significant increase in the high VT group [serum IL-1β (ng/L): 104.2±15.1 vs. 20.3±8.3, IL-6 (ng/L): 46.6±11.5 vs. 22.7±7.5, TNF-α (ng/L): 39.4±6.5 vs. 5.4±1.9, MPO (ng/L): 0.66±0.24 vs. 0.06±0.03, MIP-2 (ng/L): 109.2±25.8 vs. 22.8±8.4; BALF IL-1β (ng/L): 121.5±25.6 vs. 24.0±7.5, IL-6 (ng/L): 136.7±32.7 vs. 31.4±10.5, TNF-α (ng/L): 98.0±14.8 vs. 10.1±2.6, MPO (ng/L): 0.80±0.31 vs. 0.08±0.04, MIP-2 (ng/L): 144.4±28.9 vs. 41.2±20.7; all P < 0.01]. (4) There were only a few p-ERK, Rac1 and F-actin positive expressions in the spontaneous breathing group. The positive expressions in normal VT group were increased. In high VT group, the positive expression of p-ERK was significantly increased; Rac1 and F-actin were mainly distributed in the cell membrane and cytoplasm respectively, the positive expressions were further enhanced. (5) The gene expressions of ERK and Rac1, and protein expressions of p-ERK, Rac1 and F-actin in the high VT group were significantly higher than those in the spontaneous breathing group and normal VT group [ERK mRNA (2-ΔΔCt): 8.23±2.83 vs. 1, 3.02±1.38, p-ERK protein (gray value): 1.15±0.36 vs. 0.61±0.23, 0.88±0.22; Rac1 mRNA (2-ΔΔCt): 4.45±2.26 vs. 1, 1.22±0.39, Rac1 protein (gray value): 0.91±0.16 vs. 0.48±0.11, 0.55±0.10; F-actin protein (gray value): 0.70±0.09 vs. 0.49±0.08, 0.55±0.04; all P < 0.01]. F-actin expression in lung tissue was up-regulated in rats with VILI, which resulted in reconstruction of AEC II cyto-skeleton, and variation of cell membrane permeability through Rac1/MAPK/ERK signaling pathway during VILI.

Role and mechanism of mitophagy in ventilator-induced lung injury in rats

To explore the role and mechanism of mitophagy in ventilator-induced lung injury (VILI) in rats. Thirty-six adult Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 12): spontaneous breathing group (CON group), normal tidal volume (VT) group (NVT group, VT was 8 mL/kg) and high VT group (HVT group, VT was 40 mL/kg). All rats received endotracheal tube by tracheostomy. The rats in CON group were maintained spontaneous breathing, while those in NVT and HVT groups received mechanical ventilation with corresponding VT. After 4 hours of ventilation, the serum, bronchoalveolar lavage fluid (BALF) and lung tissues were harvested. The lung wet/dry weight (W/D) ratio was assessed, and the histopathology changes were observed by light microscopy, and the ultra structure changes in type II alveolar epithelial cell (AEC II) were observed by electron microscopy. The levels of interleukin (IL-1β and IL-6) and tumor necrosis factor-α (TNF-α) in serum and BALF were determined by enzyme linked immunosorbent assay (ELISA). The total protein in BALF was measured by bicinchoninic acid methods, and the infiltrated cells in BALF were counted. The mRNA expressions and protein levels of microtube associated light chain 3B (LC3B), mitochondrial DNA coded cytochrome C oxidase IV (COX-IV) and nuclear factor-KB p65 (NF-KB p65) in lung tissues were determined by real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-qPCR) and Western Blot. The histopathology of lung tissue and the ultra structure of AEC II were normal in CON group and NVT group, and the obvious inflammatory changes and pathological injury were found in HVT group. Compared with CON and NVT groups, the W/D ratio in HVT group was significantly increased (8.53±1.05 vs. 5.12±0.65, 5.57±0.55, both P < 0.05), and total protein, infiltrated cells, and IL-1β, IL-6 and TNF-α in BALF were significantly increased [total protein (g/L): 2.35±0.45 vs. 1.46±0.34, 1.76±0.51; infiltrated cells (×105/mL): 2.05±0.48 vs. 0.40±0.08, 0.60±0.23; IL-1β (ng/L): 119.82±6.56 vs. 76.15±3.32, 79.39±4.44; IL-6 (μg/L): 4.10±0.52 vs. 1.97±0.40, 2.27±0.36; TNF-α (mg/L): 1.49±0.28 vs. 0.43±0.23, 0.61±0.24; all P < 0.05], IL-1β, IL-6 and TNF-α levels in serum were also elevated [IL-1β (ng/L): 127.53±7.10 vs. 79.40±2.80, 82.95±2.25; IL-6 (μg/L): 6.28±0.82 vs. 2.96±0.35, 3.36±0.72; TNF-α (mg/L): 1.59±0.42 vs. 0.53±0.22, 0.78±0.25; all P < 0.05]. The mRNA expressions and protein levels of LC3B, COX-IV and NF-KB p65 in lung tissue of HVT group were significantly higher than those of CON group and NVT group, the mRNA expressions of LC3B-II, COX-IV and NF-KB p65 were (3.52±0.90), (3.76±1.16) and (9.54±2.06) folds of those in CON group, and the protein expressions were (1.76±0.24), (1.65±0.20) and (1.91±0.12) folds of those in CON group, with significantly statistical differences (all P < 0.05). There were no significant differences in the parameters mentioned above between NVT group and CON group. Mitophagy may be associated with VILI resulting from escaped mitochondrial DNA for activation of inflammation.

SN50, a Cell-Permeable Inhibitor of Nuclear Factor-κB, Attenuates Ventilator-Induced Lung Injury in an Isolated and Perfused Rat Lung Model.

High tidal volume (VT) ventilation causes the release of various mediators and results in ventilator-induced lung injury (VILI). SN50, a cell-permeable nuclear factor-κB (NF-κB) inhibitory peptide, attenuates inflammation and acute respiratory distress syndrome. However, the mechanisms associated with the effects of SN50 in VILI have not been fully elucidated. We investigated the cellular and molecular mechanisms for the effects of SN50 treatment in VILI. An isolated and perfused rat lung model was exposed to low (5 mL/kg) or high (15 mL/kg) VT ventilation for 6 h. SN50 was administered in the perfusate at the onset of the high-stretch mechanical ventilation. The hemodynamics, lung histological changes, inflammatory responses, and activation of apoptotic pathways were evaluated. VILI was demonstrated by increased pulmonary vascular permeability and lung weight gain, as well as by increased levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), hydrogen peroxide, and macrophage inflammatory protein-2 in the bronchoalveolar lavage fluid. The lung tissue expression of TNF-α, IL-1β, mitogen-activated protein kinases (MAPKs), caspase-3, and phosphorylation of serine/threonine-specific protein kinase (p-AKT) was greater in the high VT group than in the low VT group. Upregulation and activation of NF-κB was associated with increased lung injury in VILI. SN50 attenuated the inflammatory responses, including the expression of IL-1β, TNF-α, MPO, MAPKs, and NF-κB. In addition, the downregulation of apoptosis was evaluated using caspase-3 and p-AKT expression. Furthermore, SN50 mitigated the increases in the lung weights, pulmonary vascular permeability, and lung injury. In conclusion, VILI is associated with inflammatory responses and activation of NF-κB. SN50 inhibits the activation of NF-κB and attenuates VILI.

Provider Bias Impacts Tidal Volume Selection and Ventilator Days in Trauma Patients

The ARDSnet (Acute Respiratory Distress Syndrome Clinical Network) study demonstrated that low tidal volume (Vt) reduces mortality from ARDS. It is unknown whether low Vt is beneficial in at-risk trauma patients. We hypothesized that Vt selection would be low in accordance with ARDSnet criteria and that subsequent outcomes would be improved. A 1-year retrospective observational study was conducted on all trauma patients aged 15 years and older and on mechanical ventilation for 48 hours or longer, excluding those with cardiopulmonary disease. Using maximum Vt, we identified low and high Vt groups (≤8 mL/predicted body weight (PBW) and >8 mL/PBW). Data collected included demographic characteristics, lengths of stay, ventilator and ICU days, ARDS, and other complications. A total of 364 patients were identified and organized into low Vt (n= 181) and high Vt (n= 183) groups. There was no difference between groups in age, Injury Severity Score, Glasgow Coma Scale, or mechanism of injury. The rate of ARDS was the same in each group. Patients with a high Vt had lower PBW (63.1 ± 8.8 vs 71.7 ± 6.9; p < 0.001), higher BMI(29.7 ± 6.9 kg/m(2) vs 26.6 ± 6.5 kg/m(2); p < 0.001), and were more likely to be female. Height was inversely correlated with Vt (r(2)=-0.579; p < 0.001). The high Vt group experienced longer ICU stays (9.9 ± 8.8 days vs 8.1 ± 7.9 days; p= 0.045) and more ventilator days (8.55 ± 10.5 days vs 6.14 ± 7.4 days; p= 0.015). Trauma patients receiving high Vt were shorter, had higher BMI, and were more likely to be female. The consequences included longer ICU stays and more ventilator days. Formal calculation of PBW and subsequent Vt is advocated.

Effect of BML-111 on ventilator-induced lung injury in rats

Objective To evaluate the effect of BML-111 on ventilator-induced lung injury in rats. Methods Forty-eight healthy male Sprague-Dawley rats, weighing 200-250 g, aged 6-8 weeks, were randomized into 6 groups (n=8 each) using a random number table: control group (C group), low tidal volume (VT) group (LVTgroup), high VT group (HVTgroup), low dose BML-111 group (BL group), high dose BML-111 group (BH group), and BML-111 plus BOC-2 (lipoxin A4 receptor antagonist) group (BOC-2 group). Group C kept spontaneous breathing after tracheotomy, and received no mechanical ventilation.The rats in the other 5 groups were mechanically ventilated (respiratory rate 80 breaths/min, fraction of inspired oxygen 21%, positive end-expiratory pressure 0). The VT was 6 ml/kg in group LVT, or 20 ml/kg in HVT, BL, BH and BOC-2 groups.BML-111 0.1 and 1.0 mg/kg were injected intraperitoneally during ventilation in BL and BH groups, respectively.In group BOC-2, BOC-2 50 μg/kg was injected intraperitoneally before ventilation, and BML-111 1.0 mg/kg was injected intraperitoneally during ventilation.Arterial blood samples were collected at 4 h of ventilation, arterial oxygen partial pressure (PaO2) was determined.Then animals were sacrificed by exsanguination.Bronchoalveolar lavage fluid (BALF) of the left lung was collected for determination of neutrophil count, and the level of neutrophil was calculated.The right lung tissue specimens were obtained for microscopic examination, and for determination of wet/dry lung weight ratio (W/D ratio), myeloperoxidase (MPO) activity, and contents of malondialdehyde (MDA), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6. Results Compared with group C, PaO2 was significantly decreased, and the level of neutrophil in BALF, W/D ratio, MPO activity, and contents of MDA, MCP-1, TNF-α, IL-1β and IL-6 were increased in group HVT (P 0.05). Compared with group HVT, PaO2 was significantly increased, and the level of neutrophil in BALF, W/D ratio, MPO activity, and contents of MDA, MCP-1, TNF-α, IL-1β and IL-6 were decreased in group BH, and the contents of TNF-α, IL-1β and IL-6 were significantly decreased (P 0.05). Compared with group BH, PaO2 was significantly decreased, and the level of neutrophil in BALF, W/D ratio, MPO activity, and contents of MDA, MCP-1, TNF-α, IL-1β and IL-6 were increased in group BOC-2 (P<0.05). The pathological changes were significantly attenuated in group BL as compared with HVT and BOC-2 groups. Conclusion BML-111 can attenuate ventilator-induced lung injury in rats, and activated lipoxin A4 receptors are involved in the mechanism. Key words: Receptors, lipoxin; Respiration, artificial; Respiratory distress syndrome, adult

Mechanical ventilation after lung transplantation

IntroductionTo explore the hypothesis that early ventilation strategies influence clinical outcomes in lung transplantation, we have examined our routine ventilation practices in terms of tidal volumes (Vt) and inflation pressures. MethodsA total of 124 bilateral lung transplants between 2010 and 2013 were retrospectively assigned to low (<6 mL/kg), medium (6-8 mL/kg), and high (>8 mL/kg) Vt groups based on ventilation characteristics during the first 6 hours after surgery. Those same 124 patients were also stratified to low-pressure (<25 cm H2O) and high-pressure (≥25 cm H2O) groups. ResultsEighty percent of patients were ventilated using pressure control mode. Low, medium, and high Vt were applied to 10%, 43%, and 47% of patients, respectively. After correcting for patients requiring extracorporeal support, there was no difference in short-term to midterm outcomes among the different Vt groups. Low inflation pressures were applied to 61% of patients, who had a shorter length of intensive care unit stay (5 vs 12 days; P = .012), higher forced expiratory volume in 1 second at 3 months (77.8% vs 60.3%; P < .001), and increased 6-month survival rate (95% vs 77%; P = .008). ConclusionLow Vt ventilation has not been fully adopted in our practice. Ventilation with higher inflation pressures, but not Vt, was significantly associated with poorer outcomes after lung transplantation.

Effects of mechanical ventilation with different tidal volumes on coagulation/fibrinolysis in rabbits with acute respiratory distress syndrome

To observe the effects of mechanical ventilation with different tidal volumes (VT) on coagulability and fibrinolytic characteristics in rabbits with acute respiratory distress syndrome (ARDS) induced by two-hits with oleic acid (OA) and lipopolysaccharide (LPS). Forty healthy adult male rabbits were randomly divided into five groups (8 rabbits in each group): sham operation group, model group, low VT group (6 mL/kg), rontine VT group (10 mL/kg ), high VT group (15 mL/kg). ARDS model was reproduced by sequential injection of 0.1 mL/kg OA and 500 μg/kg LPS via auricular vein, and the rabbits in sham operation group received normal saline in same volume. Mechanical ventilation was performed in different VT groups after model reproduction, and the end of the experiment was determined as 6 hours after LPS injection. Blood was collected from the carotid artery at 30 minutes and 360 minutes after LPS injection, with which arterial partial pressure of oxygen (PaO2) was determined, and oxygenation index was calculated. Internal jugular vein blood was collected at 5, 120, 240, and 360 minutes after LPS injection, and activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib) and antithrombin III (AT-III) were determined. The blood was collected at the end of the experiment, and then the rabbits were sacrificed, and serum levels of procollagen type III (PIIIP), plasminogen activator inhibitor-1 (PAI-1) as well as PIIIP level in lung tissue were determined. The wet/dry weight ratio (W/D) of lung tissues was calculated. Compared with sham operation group, oxygenation index at both 30 minutes and 360 minutes were significantly decreased in model group, while W/D ratio was significantly increased. PT and APTT at 5 minutes were significantly shortened followed by a gradual increase. Fib and AT-III showed no change at 5 minutes followed by a gradual decrease, while serum PAI-1 and PIIIP as well as PIIIP in lung tissue were significantly increased. There was no significant difference in oxygenation index between all VT groups and model group, with a tendency to increase in low VT group. W/D ratio in low VT group was the lowest (5.09±0.19), and it was significantly lower than that of the model group (6.02±0.27, P<0.01), while it was the highest in high VT group (6.27±0.32). PT and APTT in all VT groups were gradually prolonged, and Fib and AT-III were gradually decreased. PT and APTT in low VT group were significantly shorter than those in model group from 120 minutes on [PT (s): 120 minutes: 8.90±0.28 vs. 11.43±0.28, 240 minutes: 9.18±0.21 vs. 11.99±0.50, 360 minutes: 9.25±0.15 vs. 12.49±0.29; APTT (s): 120 minutes: 69.09±3.91 vs. 76.08±4.21, 240 minutes: 67.53±2.14 vs. 79.71±2.25, 360 minutes: 66.95±1.13 vs. 83.21±4.01, all P<0.05], Fib (g/L) was significantly elevated (120 minutes: 3.80±0.09 vs. 3.38±0.15, 240 minutes: 3.91±0.05 vs. 2.47±0.16, 360 minutes: 4.06±0.13 vs. 2.39±0.16, all P<0.05), and no significant difference was found in AT-III. Serum contents of PAI-1 and PIIIP as well as PIIIP in lung tissue were significantly lowered [ serum PAI-1 (ng/L): 1.14±0.26 vs. 1.63±0.91, serum PIIIP (ng/L): 1.62±0.52 vs. 2.91±0.64, lung PIIIP (ng/L): 4.40±0.58 vs. 5.75±0.47, all P<0.01]. The change tendency of all parameters in routine VT group was lower than that in low VT group, PT at 120 minutes and 360 minutes, APTT at 240 minutes and 360 minutes was significantly shorter than that in model group, and Fib at 120 minutes and 240 minutes were significantly higher than those in model group (all P<0.05). No significant difference was found in AT-III, serum PAI-1 and PIIIP as well as lung PIIIP as compared with model group. PT and APTT at 360 minutes in high VT group were significantly longer than those in model group, Fib at 360 minutes was significantly lower than that in model group, and lung PIIIP was significantly higher than that in model group. There are some important changes in coagulability which changes from a hyper state into a hypo coagulate state, while fibrinolysis is inhibited during the pathological process of ARDS produced by two-hit of OA and LPS. Mechanical ventilation with low VT can obviously improve coagulability and fibrinolytic status, while ventilation with routine VT has little effect on coagulability and fibrinolytic status. Mechanical ventilation with high VT, however, will greatly deteriorate the coagulability and fibrinolytic function in ARDS.

Effect of airway humidification on lung injury induced by mechanical ventilation

To explore the effect of airway humidification on lung injury as a result of mechanical ventilation with different tidal volume (VT). Twenty-four male Japanese white rabbits were randomly divided into four groups: low VT with airway humidification group, high VT with airway humidification group, low VT and high VT group without humidification, with 6 rabbits in each group. Mechanical ventilation was started after intubation and lasted for 6 hours. Low VT denoted 8 mL/kg, while high VT was 16 mL/kg, fraction of inspired oxygen (FiO₂) denoted 0.40, positive end-expiratory pressure (PEEP) was 0. Temperature at Y piece of circuit in airway humidification groups was monitored and controlled at 40 centigrade. Arterial blood gas analysis, including pH value, arterial partial pressure of oxygen (PaO₂), arterial partial pressure of carbon dioxide (PaCO₂), lung mechanics indexes, including peak airway pressure (P(peak)) and airway resistance (Raw), and lung compliance was measured at 0, 2, 4, 6 hours of mechanical ventilation. The levels of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in plasma and bronchoalveolar lavage fluid (BALF) were determined by enzyme linked immunosorbent assay (ELISA). The animals were sacrificed at the end of mechanical ventilation. The wet to dry (W/D) ratio of lung tissues was calculated. Histopathologic changes in the lung tissueies were observed with microscope, and lung injury score was calculated. Scanning and transmission electron microscopies were used to examine the integrity of the airway cilia and the tracheal epithelium. Compared with low V(T) group, pH value in high V(T) group was significantly increased, PaCO₂was significantly lowered, and no difference in PaO₂was found. P(peak), Raw, and lung compliance were significantly increased during mechanical ventilation. There were no significant differences in blood gas analysis and lung mechanics indexes between low V(T) with airway humidification group and low V(T) group. Compared with high V(T) group, PaCO₂in high V(T) with airway humidification group was significantly decreased, Ppeak raised obviously, and no difference in pH value, PaO₂, Raw and pulmonary compliance was found. Compared with low V(T) with airway humidification group, no difference in blood gas analysis (PaCO2, mmHg, 1 mmHg=0.133 kPa) was found, but Ppeak (cmH₂O, 1 cmH₂O=0.098 kPa), Raw (cmH₂O), and lung compliance (mL/cmH₂O) were increased significantly in high V(T) with airway humidification group (PaCO₂at 2 hours: 27.96 ± 4.64 vs. 36.08 ± 2.11, 4 hours: 28.62 ± 2.93 vs. 34.55 ± 5.50, 6 hours: 29.33 ± 2.14 vs. 35.01 ± 5.53; Ppeak at 0 hour: 14.34 ± 1.97 vs. 8.84 ± 1.32, 2 hours: 17.33 ± 0.52 vs. 11.17 ± 2.14, 4 hours: 17.83 ± 0.98 vs. 12.67 ± 2.06, 6 hours: 18.67 ± 1.22 vs. 13.50 ± 2.16; Raw at 0 hour: 37.36 ± 5.14 vs. 27.0 5 ± 2.93, 2 hours: 43.94 ± 6.58 vs. 31.95 ± 3.56, 4 hours: 48.04 ± 6.07 vs. 35.24 ± 3.50, 6 hours: 50.33 ± 6.34 vs. 36.66 ± 3.64; pulmonary compliance at 6 hours: 2.28 ± 0.18 vs. 1.86 ± 0.37, all P<0.05). The lung W/D ratio in high VT group was significantly higher than that of the low V(T) group (6.17 ± 2.14 vs. 3.50 ± 1.52, P<0.05). W/D in high V(T) with airway humidification group was higher than that of low V(T) with airway humidification group but without statistically significant difference (5.17 ± 2.14 vs. 3.00 ± 1.10, P>0.05). Microscopic observation showed that cilia were partially detached, adhered and sparse in low V(T) group, while cilia in high V(T) group showed serious detachment and lodging. Remaining cilia were sparse, with lodging, and cellular structure was damaged. Lung tissue pathological injury score in the high V(T) group was significantly higher than that of low V(T) group (6.17 ± 2.14 vs. 3.50 ± 1.52, P<0.05). Cilia density and cellularity were normal in low V(T) with airway humidification group, and no difference in lung tissue pathological injury score was found compared with low V(T) group (3.00 ± 1.10 vs. 3.50 ± 1.52, P>0.05). Cilia were severely detached, adhered and lodging, and cellularity were not obvious in high V(T) with airway humidification group, and lung tissue pathological injury score was elevated significantly than that of the low V(T) with airway humidification group but without statistically significant difference (5.17 ± 2.14 vs. 3.00 ± 1.10, P>0.05). TNF-α and IL-8 concentrations showed no change in plasma and BALF in all groups during ventilation, and no significant difference was found among the groups. Airway humidification can alleviate pathological lung injury, damage of cilia and cellular structure in trachea caused by mechanical ventilation with low and high V(T). High V(T) with humidification can result in serious pulmonary edema.

Effect of mechanical ventilation with different tidal volumes on pulmonary surfactant in dogs during cardiopulmonary resuscitation

Objective To observe the effects of mechanical ventilation with different tidal volumes (Vt) on the pulmonary surfactant in dogs during cardiopulmonary resuscitation (CPR) and discuss the strategy of mechanical ventilation for CPR.Methods A total of 24 healthy,adult and mongrel canines were randomly (random number) divided into three groups,namely control group (A),low Vt group (B) and high Vt group (C).Canines without ventricular fibrillation in group A were not supported with mechanical ventilation,while canines in group B and group C were induced to get ventricular fibrillation (VF) with pacing catheter inserted through right external carotid vein into the right ventricle.CPR was initiated with mechanical ventilation with different Vt for 6 hours after ventricular fibrillation.The Vt set in group B was 6 ml/kg body weight and Vt set in group C was 20 ml/kg body weight.The arterial blood gas analyses were tested in different intervals.The levels of phosphatidylchline in bronchia alveolus lavage fluid (BALF) was assayed with high performance liquid chromatography (HPLC).The ratio of wet and dry weight and the morphological change scores of lung tissue were calculated.Results After ventricular fibrillation,pH,PaO2 in both groups B and C decreased and PaCO2 increased in comparison with those before VF (P ＜ 0.05),while pH,PaO2 and PaCO2 were improved after mechanical ventilation.These was statistical difference in PaCO2 between group B and group C 2 h after mechanical ventilation (P ＜ 0.05).There was difference in HCO3-between group B and group C 6 h after ROSC.The rate of successful restoration of spontaneous circulation (ROSC) and the 72 h survival rate were 75％ and 50％ respectively in group B,and 62.5％ and 40％ respectively in group C.There were no statistically different between two groups (P ＞ 0.05).The levels of phosphatidylchline in BALF of group B and C greatly decreased compared with the group A (All P ＜0.01),while phosphatidylcholine detected in the group C decreased much more than that in the group B (P ＜0.01).The W/D ratio and morphological change scores in the group C were higher than those in the group B (P ＜ 0.01).Conclusion Low tidal volume ventilation can reduce the loss of pulmonary surfactant and mitigate pulmonary injury.Therefore it may be a protective ventilation strategy after resuscitation. Key words: Cardiopulmonary resuscitation; Mechanical ventilation ; Tidal volumes ; Lung injury ; Pulmonary surfactant

Effects of low and high tidal volume and pentoxifylline on intestinal blood flow and leukocyte-endothelial interactions in mechanically ventilated rats

BACKGROUND: The combination of high PEEP and low tidal volume (VT) decreases some risks of mechanical ventilation, including pulmonary overdistention, damage due to cyclic opening and closing of the alveoli, and inflammatory responses that can lead to multiple-organ dysfunction. We hypothesized that high VT and high PEEP induce mesenteric microcirculatory disturbances and that those disturbances would be attenuated by pentoxifylline, which is anti-inflammatory. METHODS: We anesthetized (isoflurane 1.5%), tracheostomized, and mechanically ventilated 57 male Wistar rats with PEEP of 10 cm H2O and FIO2 of 0.21 for 2 hours. One group received low VT (7 mL/kg), another group received high VT (10 mL/kg), and a third group received high VT plus pentoxifylline (25 mg/kg). We measured mean arterial pressure, respiratory mechanics, mesenteric blood flow, and leukocyte-endothelial interactions. RESULTS: The mean arterial pressure was similar among the groups at baseline (108 mm Hg [IQR 94–118 mm Hg]) and after 2 hours of mechanical ventilation (104 mm Hg [IQR 90–114 mm Hg]). Mesenteric blood flow was also similar between the groups: low VT 15.1 mL/min (IQR 12.4–17.7 mL/min), high VT 11.3 mL/min (IQR 8.6– 13.8 mL/min), high-VT/pentoxifylline 12.4 mL/min (10.8–13.7 mL/min). Peak airway pressure after 2 hours was lower (P .03) in the low-VT group (10.4 cm H2O [IQR 10.2–10.4 cm H2O]) than in the high-VT group (12.6 cm H2O [10.2–14.9 cm H2O]) or the high-VT/pentoxifylline group (12.8 cm H2O [10.7–16.0 cm H2O]). There were fewer adherent leukocytes (P .005) and fewer migrated leukocytes (P .002) in the low-VT group (5 cells/100 m length [IQR 4–7 cells/100 m length] and 1 cell/5,000 m 2 [IQR 1–2 cells/5,000 m 2 ], respectively) and the high-V T /pentoxifylline group (5 cells/100 m length [IQR 3–10 cells/100 m length] and 1 cell/5,000 m 2 [IQR 1–3 cells/ 5,000 m 2 ], respectively) than in the high-V T group (14 cells/100 m length [IQR 11–16 cells/ 100 m length] and 9 cells/5,000 m 2 [IQR 8–12 cells/5,000 m 2 ], respectively). CONCLUSIONS:

Establishment of a rabbit model of acute lung injury induced by one-lung ventilation

Objective To establish a rabbit model of acute lung injury induced by one-lung ventilation (OLV) .Methods Sixteen New Zealand white rabbits weighing 2.3-2.7 kg were randomly divided into 2 groups (n=8 each):conventional tidal volume(VT) group (group Ⅰ) and high VT group (group Ⅱ).All the rabbits were tracheostomized and a tracheal tube was inserted into the right bronchus for right lung ventilation in the two groups. VT was set at 6 ml/kg in group Ⅰ and at 12 ml/kg in group Ⅱ and the other ventilatory parameters were the same in the two groups (FiO2 50% , RR 40 bpm, I∶E=1∶2). Immediately before OLV(T0) and at 1, 2 and 3 h of OLV (T1-3), peak airway pressure was measured and arterial blood samples were taken for blood gas analysis and oxygenation index (OI) was calculated. The animals were sacrificed at 3 h of OLV and lung tissues obtained for microscopic examination.The lung injury was scored. W/D lung weight ratio was calculated. Bron-choalveolar lavage fluid (BALF) was collected for measurement of protein concentrations and neutrophil counts. Results The peak airway pressure was significantly higher at T1-3 in group Ⅱ and OI was significantly lower at T2,3 in the two groups than those at T0(P＜0.05) .W/D lung weight ratio and lung injury scores of the right lung were significantly lower than those of the left lung in the two groups(P＜0.05).The peak airway pressure was significantly higher at T1-3, OI was significantly lower at T3, and W/D lung weight ratio, protein concentrations and neutrophil counts in BALF and lung injury scores of the right lung were significantly higher in group Ⅱ than in group Ⅰ(P＜0.05). Conclusion OLV with VT of 12 ml/kg for 3 h can successfully establish a rabbit model of acute lung injury. Key words: Respiration, artificial; Respiratory distress syndrome,adult; Disease models,animal