Objective To investigate the effects of different levels of intra-abdominal pressure ( IAP) on respiration and hemodynamics in a porcine model of acute lung injury( ALI) .Methods A total of 8 domestic swine received mechanical ventilation. Following baseline observations, oleic acid 0. 1mL/kg in 20mL of normal saline was infused via internal jugular vein. Using a nitrogen gas pneumoperitongum, the IAP increased from0 to 15 and 25mmHg, and the groups were named IAP0 , IAP15 and IAP25 , respectively. During the experimental period, hemodynamic parameters including heart rate ( HR) , cardiac output ( CO) , mean arterial pressure( MAP) , central venous pressure( CVP) , intrathoracic blood volume index( ITBVI) and so on were obtained by using thermodilution technique of pulse induced continuous cardiac output( PiCCO) . The esophageal pressure( Pes) was dynamicly monitored by the esophageal catheter. Results Pes and peak airway pressure( Ppeak) increased and static lung compliance( Cstat) decreased significantly in IAP15 and IAP25 groups compared with IAP0 group( all P lt;0. 01) . Transpulmonary pressure( Ptp) showed a downward trend( P gt;0. 05) . PO2 and oxygenation index showed a downward trend while PCO2 showed a upward trend ( P gt;0. 05) . HR and CVP increased significantly, cardiac index( CI) and ITBV index decreased significantly ( all P lt;0. 05) ,MAP didn′t change significantly( P gt;0. 05) . The changes in Pes were negatively correlated with the changes in CI( r = - 0. 648, P = 0. 01) . Conclusion In the porcine model of ALI, Pes increases because of a rise in IAP which decreased pulmonary compliance and CI.
ObjectiveTo evaluate systematically the relationship between obesity and clinical prognosis in acute respiratory distress syndrome (ARDS) patients.MethodsA systematic search was performed in Pubmed, EMBASE, Cochrane databases, Wiley, Ovid, Medline, CNKI, VIP and Wanfang. All studies that reported obesity in the clinical prognosis of ARDS and acute lung injury were included. A meta-analysis was performed using RevMan 5.0 and Stata 10.0.ResultsA total of 28 368 patients from 9 studies were included in this meta-analysis. The combined results showed that obesity was associated with the decreased mortality of ARDS [odds ratio(OR)=0.63, 95% confidence intervals (95%CI) 0.41 to 0.98, P=0.04]. In subgroup analysis, the result showed no obvious relationship between obesity and 28-day mortality in ARDS/ALI (OR=0.92, 95%CI 0.55 to 1.54, P=0.76). However, obesity was associated with lower risk of 60days and 90-day mortality in ARDS/ALI (60-day: OR=0.84, 95%CI 0.75 to 0.94, P=0.002; 90-day: OR=0.38, 95%CI 0.22 to 0.66, P=0.000 5). Compared with normal weight patients with ARDS, hospital length of stay, ICU length of stay, and duration of mechanical ventilation did not differ significantly [hospital length of stay: weighted mean difference (WMD)=3.61, 95%CI –0.36 to 7.57, P=0.07; intensive care unit (ICU) length of stay: WMD=1.52, 95%CI –0.22 to 3.26, P=0.09; duration of mechanical ventilation: WMD=–0.50, 95%CI –2.18 to 1.19, P=0.56], but ventilator-free days was significantly longer in obese patients (WMD=2.68, 95%CI 0.86 to 4.51, P=0.004).ConclusionsObesity is not associated with hospital length of stay, ICU length of stay, and duration of mechanical ventilation in patients with ARDS. However, obesity is associated with a reduction of long-term mortality and increased ventilator-free days in the patients with ARDS. Additional larger randomized controlled studies are needed to confirm the possible role of obesity in the clinical prognosis of ARDS.
Objective To observe the protective effects of ambroxol hydrochloride ( AMB) on rabbit model of acute lung injury ( ALI) induced by oleic acid and explore its mechanisms. Methods The ALI model of rabbit was induced by oleic acid. Twenty-four Japanese white rabbits were divided into three groups randomly, ie. a normal saline group ( NC group) , an ALI group and an ALI plus ambroxol injection group ( AMB group) . The pathological changes and apoptotic index ( AI) in lung tissue, Caspase-3 activity in lung tissue homogenate were observed 6 hours after the intervention. Serum activity of superoxide dismutase ( SOD) and serum levels of malonaldehyde ( MDA) , interleukin-1β( IL-1β) , and tumor necrosis factor-α ( TNF-α) were measured simutanously. Results The pathological injury of lung in the AMB group was milder than that in the ALI group. Both the AI in lung tissue and Caspase-3 activity in homogenate in the AMB group were lower than those in the ALI group significantly ( P lt;0. 01, P lt;0. 05 respectively) , butwere higher than those in the NC group( both P lt; 0. 01) . The activity of SOD in serum measured 6 hours after AMB intervention was higher while the serum levels of MDA, IL-1βand TNF-αin serum were lower ( P lt;0. 01) than those in the ALI group significantly ( all P lt;0. 01) . Conclusions Ambroxol hydrochloride has protective effects on oleic acid-induced acute lung injury. The mechanisms may be related to inhibition of oxidative stress and suppression of cytokines synthesis ( IL-1βand TNF-α) , the activity of the Caspase-3,and the apoptosis of lung tissue.
ObjectiveTo observe the effects of aquaporin 1 (AQP1) on the proliferation and migration of endothelial progenitor-endothelial progenitor cells (EPC).MethodsBone marrow cells of AQP1 wild-type (WT) (n=6) and knockout-type (KO) mice (n=6) were isolated and differentiated into EPC in vitro. Immunofluorescence was used to detect cell surface antigens to identify EPC. Live cell kinetic imaging and quantification technology, transwell migration assays, as well as scratch test were used to compare the function of EPC between AQP1 WT and KO mice.ResultsEPC culture showed that cells were initially suspended and gradually adhered to typical mesenchymal stem cells within 7 days. After cultured on special medium for endothelial cells they were adhered and differentiated, and fusiform or polygonal, paving stone-like EPC were observed around 14 days. When cultured by special medium of EPC, CD133 and CD31 were positively detected after 7 days, and CD34 and Flk-1 were positively detected after 14 days. Positive expression of AQP1 was only detected in EPC of AQP1 WT mice. Functional studies of EPC revealed there was no significant difference in the proliferation of EPC between AQP1 WT and KO group mice. Transwell assay showed that EPC migration ability of AQP1 KO mice was significantly weaker than that of WT mice. The scratch healing ability of EPC in AQP1 KO mice was significantly lower than that of WT mice.ConclusionsEPC initially shows the characteristics of stem cells and with the prolongation of culture time, EPC gradually shows the characteristics of endothelial cells. AQP1 affects the EPC migration rather than proliferation.
Objective To explore the expression of myeloid differentiation protein2 ( MD-2) in rat lung and its role in acute lung injury ( ALI) induced by lipopolysaccharide ( LPS) . Methods Twenty male SD rats were randomly divided into a LPS group and a control group. The wet/dry ratios of lung tissues were measured and the histological changes of lung tissues were observed under microscope. Alveolar macrophages were collected from bronchial alveolar lavage fluid ( BALF) . The MD-2 mRNA and protein expressions were detected by RT-PCR, Western blot, and immunohistochemistry respectively. The MD2-siRNA oligo were transfected into NR8383 cells and 1 μg/mL LPS was used to stimulate the cells. The expressions of MD-2 mRNA and protein were detected by RT-PCR and Western blot. The levels of TNF-αin rat serum and cell culture supernatant were detected by ELISA. Results Compared with the control group, the expressions of MD-2 mRNA and protein in alveolar macrophages and lung tissue were elevated ( P lt;0. 01) , as well as the level of TNF-αin rat serum. The expressions of MD-2 mRNA and protein in NR8383 cell and the level ofTNF-αin supernatant increased obviously after LPS stimulation ( P lt;0. 01) . There were no changes of MD-2 mRNA and protein expressions and TNF-α of NR8383 cells treated by MD-2 siRNA with or without LPS stimulation ( P gt;0. 05) . Conclusions The expression of MD-2 in lung increases obviously after challengedby LPS. KnockdownMD-2 gene of NR8383 cell byMD-2 siRNA can inhibit TNF-αsecretion induced by LPS stimulation.MD-2 may play an important role in rat ALI induced by LPS.
Objective To investigate the pathogenesis of acute lung injury in rats induced by intra-peritoneally injection of perforative peritonitis ascitic fluids（PPAF） and the role of L-arginine （L-Arg） in acute lung injury in this model. Methods Perforative peritonitis （PP） models were established in 60 rats and PPAF were collected. Forty-eight rats were randomly divided equally into NS group，PPAF group, and L-Arg group. Rats were randomly subjected to death at 7 h and 12 h. Peripheral blood WBC were counted，levels of NO and malondialdehyde （MDA） in serum were examined. Lung injury score and wet/dry ratio were evaluated， and level of myeloperoxidase （MPO） in lung tissues and lung cell apoptosis were tested. Results WBC count of peripheral blood, levels of NO and MDA in serum， level of MPO in lung tissue, lung injury score， wet/dry ratio， and lung cell apoptosis rate in PPAF group were significantly higher than that in NS group at each time point（P＜0.01）. Level of NO in serum in L-Arg group was higher than that in PPAF group （P＜0.01）， but lower level of MDA in serum， lower level of MPO in lung tissue and lung injury score，lower wet/dry ratio， and lung cell apoptosis rate were observed in L-Arg group（P＜0.05）. In PPAF group and L-Arg group， level of NO in serum， wet/dry ratio, and lung cell apoptosis rate were higher at 12 h than that at 7 h（P=0.000）. Serum NO level was in negative correlation with serum MDA level （r=-0.257，P=0.021）， MPO level in lung tissue（r=-0.444， P=0.011），and lung cell apoptosis（r=-0.351， P =0.010） in PPAF group and L-Arg group， but serum MDA level was in positive correlation with cell apoptosis（r=0.969， P＜0.001） in each group. Conclusions Acute lung injury rats model can be established by intra-peritoneally injection of PPAF. Enhanced oxidizing reaction and cell apoptosis take part in the occurrence of acute lung injury. L-Arg plays a protective role in acute lung injury.
Objective To assess the efficacy of ambroxol on acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) . Methods The randomized controlled study involving ambroxol on ALI/ARDS were searched and identified from Cochrane Library, PubMed, China Academic Journals Full-text Database, Chinese Biomedical Literature Database, WanFang Resource Database, and Chinese Journal Fulltext Database. The quality of the chosen randomized controlled studies was evaluated, and then the valid data was extracted for meta-analysis. Results Ten articles were included, all in Chinese, including 459 cases ofpatients ( 233 cases in experimental group,226 cases in control group) , with baseline comparability between the various experiments. Systematic review showed that in ALI/ARDS patients, high-dose ambroxol was in favor to improve PaO2 [ WMD =12. 23, 95% ( 9. 62, 14. 84) , P lt; 0. 0001] and PaO2 /FiO2 [ WMD = 32. 75,95% ( 30. 00, 35. 51) , P lt;0. 0001] , reduce lung injury score [ WMD = - 0. 49, 95% ( - 0. 66, - 0. 33) ,P lt;0. 0001] , decrease the duration of mechanical ventilation [ WMD = - 2. 70, 95% ( - 3. 24, - 1. 12) ,P lt;0. 0001] and the length of ICU stay [ WMD= - 2. 70, 95% ( - 3. 37, - 2. 04) , P lt;0. 0001] , and lower mortality [ OR=0. 46,95%( 0. 22, 1. 00) , P = 0. 05] . Conclusions The existing clinical evidence shows that, compared with conventional therapy, high-dose ambroxol plus can significantly improve PaO2 , PaO2 /FiO2 , lung injury score, duration of mechanical ventilation, length of ICU stay and mortality in ALI/ARDS patients. Due to the quality of research and the limitations of the study sample, there likely to exist a bias,and may affect the strength of result, so we expect more high-quality, large-scale randomized controlled clinical trial to verify.
ObjectiveTo explore the therapeutic effect of angiotensin-converting enzyme 2 (ACE2) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a rat model.
MethodsTwenty-four Wistar rats were randomly divided into a control group, an ALI group, and an ACE2 group.The rat ALI model was established by intravenous injection of LPS.Then the rats in the ACE2 group received intraperitoneally injection of recombinant rat ACE2 by 0.1 mg/kg immediately after LPS injection.All rats were sacrificed 2 hours later.Rat arterial blood gas was analyzed and wet/dry (W/D) weight ratio of lung tissue was measured.Concentrations of TNF-α, IL-8 and IL-1βin lung tissue homogenates were measured by ELISA.Pulmonary pathological changes were evaluated by hematoxylin-eosin stain under light microscope.
ResultsALI induced by LPS was successfully established in the rats.ACE2 pretreatment markedly impoved PaO2 level of the ALI rats(P < 0.05), and decreased the lung W/D ratio(P < 0.05).The concentration of TNF-α, IL-8 and IL-1βin lung tissue homogenates were also inhibited by ACE2.And the lung histopathological changes and score were attenuated in the ACE2 group.
ConclusionACE2 treatment has therapeutic effects on ALI induced by LPS.
ObjectiveTo evaluate the effect of positive end-expiratory pressure (PEEP) on respiratory function and hemodynamics in acute lung injury (ALI) with intra-abdominal hypertension (IAH).
MethodsSix pigs were anesthetized and received mechanical ventilation (MV). Volume controlled ventilation was set with tidal volumn(VT) of 8 mL/kg,respiratory rate(RR) of 16 bpm,inspired oxygen concentration (FiO2) of 0.40,and PEEP of 5 cm H2O. ALI was induced by repeated lung lavage with diluted hydrochloric acid (pH<2.5) until PaO2/FiO2 declined to 150 mm Hg or less to established ALI model. Intra-abdominal hypertension was induced by an nitrogen inflator to reach intra-abdominal pressure of 20 mm Hg. Respiratory parameters and hemodynamics were continuously recorded at different PEEP levels(5,10,15,and 20 cm H2O). Every level was maintained for one hour.
ResultsPaO2/FiO2 in PEEP5,10,15 and 20 were 90±11,102±10,172±23 and 200±34 mm Hg respectively. PaO2/FiO2 in PEEP15 and 20 were significantly higher than those in PEEP5 and 10 (P<0.05). Chest wall compliance (Ccw) in PEEP5,15 and 20 were 26±3,76±15 and 85±14 mL/cm H2O respectively. Ccw in PEEP15 and 20 were significantly higher than those in PEEP5 (P<0.05). There was no significant difference in lung compliance (CL) in different PEEP levels (P>0.05). Plateau pressure(Pplat) in PEEP5,10,15 and 20 were 30±3,31±2,36±2 and 38±4 cm H2O respectively. Pplat in PEEP15 and 20 were significantly higher than those in PEEP5 and 10 (P<0.05). There was no significant difference in Pplat between PEEP15 and 20 (P>0.05). Heart rate (HR) in PEEP5,15 and 20 were 113±17,147±30,and 160±30 beat/min respectively. HR in PEEP15 and 20 were significantly higher than those in PEEP5 (P<0.05). There was no significant difference in HR between PEEP15 and 20 (P>0.05).Cardiac index (CI) in PEEP5 and 20 were 4.5±0.6 and 3.5±0.6 L·min-1·m-2 respectively. CI in PEEP20 was significantly lower than that in PEEP5 (P<0.05). There was no significant difference in CI in PEEP5,10 or 15(P>0.05). Central venous pressure(CVP) in PEEP5,15 and 20 were 12±2,17±2,and 18±3 mm Hg respectively. CVP in PEEP15 and 20 were significantly higher than those in PEEP5 (P<0.05). There was no significant difference in CVP between PEEP15 and 20 (P>0.05). There were no significant differences in MAP,SVRI,ITBVI,GEDI,PVPI,or EVLWI between different PEEP levels.
ConclusionConcomitant ALI and IAH can induce great impairments in respiratory physiology. When PEEP is gradually increased,oxygenation and the respiratory function are improved without significant secondary hemodynamic disturbances.
ObjectiveTo study the protective effect and mechanism of ophiopogonin D (OP-D) on lipopolysaccharide induced acute lung injury (ALI) in mice.MethodsFifty SPF C57BL/6 mice were randomly divided into five groups, ie. a control group, a sham operation group, a model group, an OP-D group (10 mg·kg–1·d–1), and a dexamethasone group (2 mg·kg–1·d–1), with 10 mice in each group. One day before the establishment of the model, the OP-D group and the dexamethasone group received the corresponding drugs by gavage. The model group, the OP-D group and the dexamethasone group received lipopolysaccharide (2 mg/kg, 30 μL) through the trachea to establish the ALI model. The sham operation group received the same volume of normal saline. The blank control group was not treated. Six hours after the operation, the mice were weighed and then killed for peripheral blood and lung tissue. The weight of lung tissue was measured to evaluate the degree of pulmonary edema; the pathological changes of lung tissue were observed by hematoxylin-eosin staining; the mRNA expressions of interleukin (IL)-6, IL-10, and IL-17 in lung tissue were detected by qPCR; the percentage of Th17 and Treg cells in peripheral blood was detected by flow cytometry.ResultsCompared with the model group, the degree of pulmonary edema in the OP-D group decreased significantly (P<0.05), the lung tissue injury decreased, the mRNA expressions of IL-6 and IL-17 in the lung tissue and the proportion of Th17 cells in the peripheral blood decreased significantly (P<0.05), the proportion of Treg cells in the peripheral blood and the mRNA expression of IL-10 in the lung tissue increased significantly (P<0.05).ConclusionOP-D may have therapeutic effect on LPS induced ALI in mice by regulating the balance of Th17/Treg cells.
