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.
Objective To observe whether additional penehycl idine hydrochloride (PHC) in mechanical ventilation produces therapeutic effect on oleic acid (OA) induced acute lung injury (ALI) in canine. Methods Seventeen male canines (weighing 12-17 kg) were divided into control group (n=5), OA group (n=6) and PHC group (n=6). ALI model was developed by central venous injection of OA in canines of OA and PHC groups. ALI model was kept steady in air, all groups received mechanical ventilation 90 minutes later. Three groups received normal sal ine 0.25 mg/kg without injection of OA(control group), normal sal ine 0.25 mg/kg after injection of OA (OA group) and PHC 0.25 mg/kg after injection of OA (PHCgroup) respectively at 0 h (90 minutes after onset time of ALI/ARDS). The heart rate (HR), mean arteial pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), artery blood gas analysis, cardiac output (CO), extravascular lung water index (EVLWI), FiO2 and VT were observed respectively at basel ine, onset time of ALI/ARDS and 0 h, then again at 1 hour intervals for 6 hours. Besides the above, airway peak pressure (Ppeak), airway plat pressure (Pplat), mean airway pressure (Pmean) and positve end-expriatory pressure (Peep) were also observed each hour during 1-6 hours. Oxygenation index (OI), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), alveolar-arterial differences for O2 (AaDO2) and dynamic lung compl iance (DLC) were calculated and pulmonary tissue was collected for histopathologic investigation and dry wet weight ratio (WDR) test. Results The functional parameters of PHC group were improved when compared those of OA group, but there was no siginficant difference; WDR of independent region of three groups were 80.42% ± 3.48%, 82.67% ± 4.01% and 82.26% ± 1.43% respectively; WDR of dependent region of three groups were 80.51% ± 3.60%, 83.71% ± 1.98% and 82.57% ± 1.08% respectively. WDR of PHC group were obviously improved when compared with those of OA group, but there was no significant difference. Independent and dependent regions of PHC group were significantly improved when compared those of OA group in histopathologic scores, alveolar edema, inflammatory infiltration and over-distension (P lt; 0.01). Conclusion Additional PHC in mechanical ventilation produces obvious therapeutic effect on OA induced acute lung injury in canine.
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.
Acute lung injury is one of the common and serious complications of acute aortic dissection, and it greatly affects the recovery of patients. Old age, overweight, hypoxemia, smoking history, hypotension, extensive involvement of dissection and pleural effusion are possible risk factors for the acute lung injury before operation. In addition, deep hypothermia circulatory arrest and blood product infusion can further aggravate the acute lung injury during operation. In this paper, researches on risk factors, prediction model, prevention and treatment of acute aortic dissection with acute lung injury were reviewed, in order to provide assistance for clinical diagnosis and treatment.
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.
Objective To investigate the changes in osteoprotegerin (OPG) / receptor activator of nuclear factor-κB ligand (RANKL) ratio in sepsis-associated acute lung injury (SA-ALI) and the role of regulation of this ratio on the inflammatory response in SA-ALI. Methods Eighteen C57BL/6 male mice were randomly divided into sham operation group, cecal ligation and perforation (CLP) group and RANKL group, with 6 mice in each group. Before the experiment, the RANKL group was intraperitoneally injected with 5 μg (0.2 mL) of recombinant RANKL antibody, whereas both the sham operation group and the CLP group were intraperitoneally injected with a volume-matched normal saline. One hour later, the sham operation group underwent only abdominal exploration and repositioning, while the other groups underwent the CLP surgery to induce the SA-ALI model. After 24 h of modelling, all mice were sacrificed and samples were collected. Pathological evaluation of lung tissues was performed by haematoxylin-eosin staining; enzyme-linked immunosorbent assay was used to detect serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β; while the mRNA and protein expression of OPG and RANKL, along with their ratio values, were detected by real-time polymerase chain reaction for quantitative analysis and protein immunoblotting. Results The SA-ALI mouse model was successfully established. Compared with the sham operation group, mice in the CLP group showed disturbed alveolar structure, obvious alveolar and interstitial haemorrhage and inflammatory cell infiltration, elevated serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly increased mRNA and protein expression of OPG and elevated OPG/RANKL ratio in lung tissue (P<0.05), whereas RANKL mRNA and protein expression was significantly decreased (P<0.05). Compared with the CLP group, the pathological damage of lung tissue in the RANKL group was reduced, the infiltration of alveolar and interstitial inflammatory cells was significantly improved, and the alveolar structure and morphology were more regular, with lower serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly lower mRNA and protein expression of OPG and OPG/RANKL ratio in lung tissue (P<0.05), and significantly higher mRNA and protein expression of RANKL in lung tissue (P<0.05). Conclusion The alteration of OPG/RANKL ratio may be related to the pathophysiological process of SA-ALI, and the decrease in its level may reflect the attenuation of the inflammatory response in SA-ALI.
Objective To investigate the effect and potential mechanism of bone marrow mesenchymal stem cells (BMSCs) - derived extracellular vesicles (EVs) on lung tissue injury in mice with severe acute pancreatitis (SAP). Methods A total of 24 specific pathogen free grade male C57BL/6 mice and primary mouse lung microvascular endothelial cells (PMVECs) were selected. The mice were divided into sham group, SAP group, and BMSC group, with 8 mice in each group. The mouse primary PMVECs were divided into model group [sodium taurocholate (NaTC) group], BMSC-EV group, and control group. Extraction and characterization of healthy mouse BMSCs and their derived extracellular vesicles (BMSC-EVs) were conducted. A mouse model of SAP was established, and BMSC-EVs were injected into SAP mice by tail vein or intervened in PMVECs in vitro, to observe the pathological damage of pancreatic and lung tissues, the changes of serum amylase, lipase, and inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-6 (IL-6)], the expression of inflammatory factors of lung tissues and PMVECs, and the endothelial cell barrier related proteins [E-cadherin, ZO-1, intercellular cell adhesion molecule-1 (ICAM-1)], and tight junctions between PMVECs to explore the effects of BMSC-EVs on pancreatic and lung tissues in SAP mice and PMVECs in vitro. Results BMSCs had the potential for osteogenic, chondrogenic, and lipogenic differentiation, and the EVs derived from them had a typical cup-shaped structure with a diameter of 60-100 nm. BMSC-EVs expressed the extracellular vesicle-positive proteins TSG101 and CD63 and did not express the negative protein Calnexin. Compared with the mice in the sham group, the SAP mice underwent significant pathological damage to the pancreas (P<0.05), and their serum amylase, lipase, inflammatory factor IL-6, and TNF-α levels were significantly up-regulated (P<0.05); whereas, BMSC-EVs markedly ameliorated the pancreatic tissue damage in the SAP mice (P<0.05), down-regulated the levels of peripheral serum amylase, lipase, IL-6 and TNF-α (P<0.05), and up-regulated the level of anti-inflammatory factor IL-10 (P<0.05). In addition to this, the SAP mice showed significant lung histopathological damage (P<0.05), higher neutrophils and macrophages infiltration (P<0.05), higher levels of the inflammatory factors TGF-β and IL-6 (P<0.05), as well as reduced barrier protein E-cadherin, ZO-1 expression and elevated expression of ICAM-1 (P<0.05). BMSC-EVs significantly ameliorated lung histopathological injury, inflammatory cells infiltration, inflammatory factor levels, and expression of barrier proteins, and suppressed ICAM-1 expression (P<0.05). In the in vitro PMVECs experiments, it was found that intercellular tight junctions were broken in the NaTC group, and the levels of inflammatory factors TNF-α and IL-6 were significantly up-regulated (P<0.05), the protein expression of E-cadherin and ZO-1 was significantly down-regulated (P<0.05), and the expression of ICAM-1 was significantly up-regulated (P<0.05). BMSC-EVs significantly improved intercellular tight junctions in the NaTC group and inhibited the secretion of TNF-α and IL-6 (P<0.05), up-regulated the expression of the barrier proteins E-cadherin and ZO-1, and down-regulated the expression of ICAM-1 (P<0.05). Conclusion BMSC-derived EVs ameliorate lung tissue injury in SAP mice by restoring the lung endothelial cell barrier and inhibiting inflammatory cell infiltration.
ObjectiveTo assesse the association of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) with the risk and the mortality of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). MethodsWe searched electronic databases through April 2014 for the terms "angiotensin-converting enzyme gene", "acute lung injury" and "acute respiratory distress syndrome", and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in adults. Eight studies met the inclusion criteria, comprising 498 ALI/ARDS patients, 3220 healthy controls and 1137 patients without ALI/ARDS. Three genetic models were used: the allele, dominant and recessive models. The meta-analysis was performed with RevMan 5.2 software. ResultsThe ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS compared with the healthy controls and the patient controls for any genetic model. The ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects, and OR was 2.99 (95% CI 1.87-4.76, P < 0.05), 0.36 (95% CI 0.20-0.67, P < 0.05), 4.62 (95% CI 1.71-12.45, P < 0.05) for allele I/D, genotype II/II+ID and genotype DD/II+ID, respectively. ConclusionThere is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.
ObjectiveTo compare two different ways to establish mouse model with acute lung injury (ALI) via intratracheal instillation or intraperitoneal injection of lipopolysaccharide (LPS). MethodsBALB/c mice received intraperitoneal/intratracheal administration of LPS or sham operation. Wet/dry lung weight ratio, protein concentration in bronchoalveolar lavage fluid (BALF), and lung tissue histology were examined at 0, 1, 2, 6, 12, 18, 24, 48 h after LPS administration. Tumor necrosis factor-α (TNF-α) in BALF and serum was assayed with ELISA method. ResultsLPS treatment significantly increased wet/dry lung weight ratio, BALF protein concentration and TNF-α concentration in serum and BALF. Lung tissue was damaged after LPS challenge. The mice received LPS intraperitoneal injection got a more significant lung edema than those received LPS intratracheal instillation. Inversely, LPS intratracheal instillation induced more severed microstructure destruction. ConclusionsALI animal model by LPS intratracheal instillation or intraperitoneal injection induces inflammation and tissue damage in lung. However, the degree of tissue damage or self-healing induced by two methods is different. Therefore the decision of which way to establish ALI model will depend on the study purpose.
Objective To investigate the effects of mechanical ventilation( MV) via different tidal volume ( VT) in combination with positive end expiratory pressure( PEEP) on dogs with acute lung injury( ALI) . Methods Dog model of oleic acid-induced ALI was established. And after that animals were randomized into different MV groups ( included low VT group, VT =6 mL/kg; and high VT group, VT =20 mL/kg) and ventilated for 6 h with a PEEP of 10 cmH2O. Arterial blood gas wasmeasured before, during and after ALI model was established ( at 1 h,2 h, 4 h and 6 h during MV) . The albumin concentration in BALF and pathological change of the lung tissue were evaluated in order to determine the lung injury while animals were sacrificed after 6 h MV. Results ALI model was successfully established ( 2. 50 ±0. 80) hours after oleic acid injection. Arterial pH decreased much severer in the low VT group than the high VT group( P lt;0. 01) . PaO2 and SaO2 in ventilation groups decreased after modeling but increased after MV, and PaO2 and SaO2 were significantly higher in the low VT group than the high VT group after 6 h MV( P lt;0. 05) . PaCO2 fluctuated less in the high VT group, while it increased significantly in the low VT group after MV( P lt; 0. 01) . Oxygenation index( PaO2 /FiO2 ) was lowered after modeling( P lt; 0. 01) , decreased to about 190 mm Hg after 1 h MV. And PaO2 /FiO2 in low VT group was significantly higher than the high VT group after 6 h MV( P lt; 0. 05) . BALF albumin concentration and the lung injury score in the low VT group were both significantly lower than the high VT group( both P lt; 0. 05) . Conclusions Ventilation with PEEP could improve the oxygenation of ALI dogs, and low VT ventilation improves the oxygenation better than high VT. Otherwise, low VT could induce hypercapnia and ameliorate lung injury caused by high VT MV.