Objective To investigate the protective effects of antitumor necrosis factor-α antibody （TNF-αAb） on lung injury after cardiopulmonary bypass （CPB） and their mechanisms. Methods Forty healthy New Zealand white rabbits，weighting 2.0-2.5 kg，male or female，were randomly divided into 4 groups with 10 rabbits in each group. In groupⅠ，the rabbits received CPB and pulmonary arterial perfusion. In group Ⅱ，the rabbits received CPB and pulmonary arterial perfusion with TNF-αAb. In group Ⅲ，the rabbits received CPB only. In group Ⅳ，the rabbits only received sham surgery. Neutrophils count，TNF-α and malondialdehyde （MDA） concentrations of the blood samples from the left and right atrium as well as oxygenation index were examined before and after CPB in the 4 groups. Pathological and ultrastructural changes of the lung tissues were observed under light and electron microscopes. Lung water content，TNF-α mRNA and apoptoticindex of the lung tissues were measured at different time points. Results Compared with group Ⅳ，after CPB，the rabbitsin group Ⅰ to group Ⅲ showed significantly higher blood levels of neutrophils count，TNF-α and MDA（P＜0.05），higherTNF-α mRNA expression，apoptosis index and water content of the lung tissues （P＜0.05），and significantly lower oxyg-enation index （P＜0.05） as well as considerable pathomorphological changes in the lung tissues. Compared with group Ⅱ，after CPB，the rabbits in groups Ⅰ and Ⅲ had significantly higher blood concentrations of TNF-α （5 minutes after aortic declamping，220.43±16.44 pg/ml vs.185.27±11.78 pg/ml，P＜0.05；249.99±14.09 pg/ml vs.185.27±11.78 pg/ml，P＜0.05），significantly higher apoptosis index （at the time of CPB termination，60.7‰±13.09‰ vs. 37.9‰±7.78‰，P＜0.05；59.6‰±7.74‰ vs. 37.9‰±7.78‰，P＜0.05），significantly higher blood levels of neutrophils count and MDA （P＜0.05），significantly higher TNF-α mRNA expression and water content of the lung tissues （P＜0.05），and significantly loweroxygenation index （P＜0.05） as well as considerable pathomorphological changes in the lung tissues. Compared with groupⅠ，rabbits in group Ⅲ had significantly higher above parameters （P＜0.05） but lower oxygenation index （P＜0.05） only at 30 minutes after the start of CPB. Conclusion Pulmonary artery perfusion with TNF-αAb can significantly attenuate inflammatory lung injury and apoptosis of the lung tissues during CPB.
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 discuss the risk factors of acute respiratory distress syndrome (ARDS) in patients with severe pneumonia.MethodsData of 80 patients with severe pneumonia admitted in our ICU were analyzed retrospectively, and they were divided into two groups according to development of ARDS, which was defined according to the Berlin new definition. The age, gender, weight, Acute Physiology and Chronic Health EvaluationⅡscore, lactate, PSI score and LIPS score, etc. were collected. Statistical significance results were evaluated by multivariate logistic regression analysis after univariate analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of the parameter for ARDS after severe pneumonia.ResultsForty patients with severe pneumonia progressed to ARDS, there were 4 moderate cases and 36 severe cases according to diagnostic criteria. Univariate analysis showed that procalcitonin (t=4.08, P<0.001), PSI score (t=10.67, P<0.001), LIPS score (t=5.14, P<0.001), shock (χ2=11.11, P<0.001), albumin level (t=3.34, P=0.001) were related to ARDS. Multivariate logistic regression analysis showed that LIPS ［odds ratio (OR) 0.226, 95%CI=4.62-5.53, P=0.013］ and PSI (OR=0.854, 95%CI=132.2-145.5, P=0.014) were independent risk factors for ARDS. The predictive value of LIPS and PSI in ARDS occurrence was significant. The area under ROC curve (AUC) of LIPS was 0.901, the cut-off value was 7.2, when LIPS ≥7.2, the sensitivity and specificity were both 85.0%. AUC of PSI was 0.947, the cut-off value was 150.5, when PSI score ≥150.5, the sensitivity and specificity were 87.5% and 90.0% respectively.ConclusionsPSI and LIPS are independent risk factors of ARDS in patients with severe pneumonia, which may be references for guiding clinicians to make an early diagnosis and treatment plan.
输血相关性急性肺损伤（TRALI）是发生于输血期间或输血后的罕见并发症，以急性缺氧和非心源性肺水肿为特点，因死亡率高（5%~10%）而越来越受到临床关注[1]，据2004年美国食品药品管理局（FDA）的数据，TRALI为输血相关性死亡的首要因素[2]。根据文献资料，输注血制品、含血浆制品、新鲜冰冻血浆（FFP）和血小板的TRALI发生率分别约为1/5 000[3]，1/2 000[4]，1/7 900[5]和1/432[6]。据报道，所有血制品（除白蛋白外）均可引起TRALI[7]，甚至有作者怀疑大剂量给予白细胞介素-2（IL-2）也可能导致TRALI[8]。目前，我国有关TRALI的报道较少，仅有个别死亡案例报道[9，10]，而相关的研究报道很少，这可能与我们尚未认识到TRALI的危险性，以及对其的诊断率较低有关。
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.
Objective To investigate the serumlevel of endothelin-1 ( ET-1) in patients with acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) and its clinical significance. Methods Thirty-one ALI/ARDS patients received mechanical ventilation in ICUand 25 normal subjects were recruited in the study. The patients who died in two weeks fell in death group, and the patients who did not died in two weeks fell in survival group. The serum level of ET-1 measured by EIA method were compared between thepatients with different severity of lung injury [ evaluated by American-European Consensus Conference on ARDS ( AECC) criteria and lung injury score( LIS) ] , and between the patients with different prognosis ( death or survival ) . The correlation was analyzed between the level of ET-1 and clinical parameters.Results The ET-1 level was higher in the ALI/ARDS patients than that in the control subjects [ ( 6. 18 ±4. 48) ng/L vs. ( 2. 68 ±1. 34) ng/L, P lt;0. 05] . There was no significant difference in the patients with different severity [ ALI vs. ARDS, ( 5. 43 ±4. 39) ng/L vs. ( 7. 01 ±4. 51) ng/L, P gt; 0. 05; LIS≤2. 5 vs.LISgt;2. 5, ( 5. 93 ±5. 21) ng/L vs. ( 6. 68 ±2. 76) ng/L, P gt; 0. 05] . The ET-1 level in the death group continued to increase, and higher than that in the survival group on the 5th day [ ( 7. 96 ±3. 30) ng/L vs.( 4. 36 ±3. 29) ng/L, P lt; 0. 05] . The ET-1 level was positively correlated with SIRS, SAPSⅡ and APACHEⅡ ( r = 0. 359, 0. 369 and 0. 426, respectively, P lt; 0. 05 ) , and negatively correlated with PaO2 /FiO2 and AaDO2 ( r = - 0. 286 and - 0. 300, respectively, P lt;0. 05) . Conclusion The measurementof serum ET-1 can help to evaluate the severity and prognosis of ALI/ARDS patients.
Objective To investigate the protective effect of annexin A1 (ANXA1) derived from human umbilical cord mesenchymal stem cells (HucMSCs) on lipopolysaccharide (LPS) -induced acute lung injury (ALI). Methods Six-week-old male C57BL/6 mice were randomly divided into a sham group, a LPS group, a LPS+HucMSC-cm (LPS+cm) group, a LPS+nc-cm group, and a LPS+si-cm group, with 6 mice in each group. LPS (5 mg/kg) was intratracheally injected to induce ALI model. Then, normal saline, HucMSC-cm (HucMSC conditioned medium), HucMSC-nc-cm (normal ANXA1 expression) and HucMSC-si-cm (knockout of ANXA1) were injected intratracheally with 50 μL each after LPS treatment for 4 hours. After 72 hours of LPS administration, the mice were killed, and the blood and lung tissues were retained. After corresponding treatment, the blood and lung tissues were preserved. The expression of IL-6 in peripheral blood of mice was detected by enzyme-linked immunosorbnent assay, the pathological changes of lung tissues were observed by hematoxylin-eosin staining, and the expressions of interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1) in lung tissues of each group were detected by Western blot and immunohistochemistry. Results Compared with the sham group, the lung histopathology of mice in the LPS group showed significantly increased inflammatory factor infiltration, alveolar collapse, and lung tissue structure destruction as well as lung tissue injury score and wet/dry weight ratio (W/D) increased (all P<0.05). Accordingly, IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased (all P<0.05). Compared with the LPS group, the pathological injury of lung tissue in the LPS+cm group was improved, the lung tissue injury score and the W/D ratio decreased while IL-6, VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were decreased (all P<0.05). But there were no significant differences between the LPS+cm group and the LPS+ nc-cm group (all P>0.05). Compared with the LPS+nc-cm group, lung tissue pathological injury was aggravated again, lung tissue injury score and W/D were also increased in the LPS+si-cm group (all P<0.05). IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased again (all P<0.05). Conclusion ANXA1 derived from HucMSCs has certain protective effect in LPS-induced ALI model.
ObjectiveTo investigate whether treatment of rivaroxaban, an approved oral direct coagulation factor Xa inhibitor, attenuates functional changes in LPS -induced acute lung injury (ALI) mouse.MethodsC57BL/6 mice were randomly divided into PBS group, N-LPS group, L-LPS group, and H-LPS group. In the C57BL/6 mice being fed chow containing 0.2 mg/g or 0.4 mg/g rivaroxaban for 10 days (L-LPS group and H-LPS group), plasma concentration and coagulation indices were measured. Next, the role of rivaroxaban in ALI by using mice fed by rivaroxaban was studied in a murine ALI model induced by direct intratracheal injection lipopolysaccharides (LPS). Lung injury by histopathological scoring, micro computed tomography, pulmonary edema, inflammatory cell recruitment and activity of inflammatory cytokines in lung tissue or bronchoalveolar lavage fluid (BALF) were assessed. Western blot and immunohistochemistry were performed to examine expression of multiple proteins, including myeloperoxidase, protease-activatedreceptor 2 (PAR-2) and nuclear factor kappa B (NF-κB).ResultsThe increased plasma concentration of rivaroxaban and the prolonged prothrombin time were displayed in the mice with rivaroxaban treatment. Rivaroxaban treatment groups showed significant reductions in neutrophil sequestration and preservation of the lung tissue architecture compared to the LPS positive control (P<0.05). Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels, in addition to total protein and Evans blue concentration were all significantly reduced in BALF from the mice treated with the chow containing rivaroxaban. Administration of rivaroxaban ameliorated ALI with concomitant reductions in the expression of PAR-2 and proinflammatory cytokines. LPS-induced PAR-2 increase and NF-κB activation were also suppressed by rivaroxaban in lung tissues. Furthermore, rivaroxaban inhibited the phosphorylation levels of P65 in ALI.ConclusionsThe results demonstrate that rivaroxaban effectively attenuates LPS-induced inflammatory responses by noncoagulative pathway in ALI. The beneficial effects are associated with the decreased phosphorylation of NF-κB pathways and the reduced expression of PAR-2.