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 evaluate the efficiency and associated factors of noninvasive positive pressure ventilation( NPPV) in the treatment of acute lung injury( ALI) and acute respiratory distress syndrome( ARDS) .Methods Twenty-eight patients who fulfilled the criteria for ALI/ARDS were enrolled in the study. The patients were randomized to receive either noninvasive positive pressure ventilation( NPPV group) or oxygen therapy through a Venturi mask( control group) . All patients were closely observed and evaluated during observation period in order to determine if the patients meet the preset intubation criteria and the associated risk factors. Results The success rate in avoiding intubation in the NPPV group was 66. 7%( 10/15) , which was significantly lower than that in the control group ( 33. 3% vs. 86. 4% , P = 0. 009) . However, there was no significant difference in the mortality between two groups( 7. 7% vs.27. 3% , P =0. 300) . The incidence rates of pulmonary bacteria infection and multiple organ damage were significantly lower in the NPPV success subgroup as compared with the NPPV failure group( 2 /10 vs. 4/5, P =0. 01;1 /10 vs. 3/5, P = 0. 03) . Correlation analysis showed that failure of NPPV was significantly associated with pulmonary bacterial infection and multiple organ damage( r=0. 58, P lt;0. 05; r =0. 53, P lt;0. 05) . Logistic stepwise regression analysis showed that pulmonary bacterial infection was an independent risk factor associated with failure of NPPV( r2 =0. 33, P =0. 024) . In the success subgroup, respiratory rate significantly decreased( 29 ±4 breaths /min vs. 33 ±5 breaths /min, P lt; 0. 05) and PaO2 /FiO2 significantly increased ( 191 ±63 mmHg vs. 147 ±55 mmHg, P lt;0. 05) at the time of 24 hours after NPPV treatment as compared with baseline. There were no significant change after NPPV treatment in heart rate, APACHEⅡ score, pH and PaCO2 ( all P gt;0. 05) . On the other hand in the failure subgroup, after 24 hours NPPV treatment, respiratory rate significantly increased( 40 ±3 breaths /min vs. 33 ±3 breaths /min, P lt;0. 05) and PaO2 /FiO2 showed a tendency to decline( 98 ±16 mmHg vs. 123 ±34 mmHg, P gt; 0. 05) . Conclusions In selected patients, NPPV is an effective and safe intervention for ALI/ARDS with improvement of pulmonary oxygenation and decrease of intubation rate. The results of current study support the use of NPPV in ALI/ARDS as the firstline choice of early intervention with mechanical ventilation.
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 explore the value of procalcitonin-to-albumin (PAR) in patients with acute respiratory distress syndrome (ARDS).MethodsA retrospective study was carried on patients diagnosed with ARDS from December 2016 to March 2018. The receiver-operating characteristics (ROC) curve was used to identify the cutoff value of PAR. The association of PAR and 28-day mortality was evaluated using univariate and multivariable Cox regression.ResultsIn the final analysis, there were a total of 255 patients included. Of whom 164 (64.3%) was male, 91 (35.7%) was female and the mean age was 52.1±14.5 years old. The 28-day mortality of all the patients was 32.9% (n=84). ROC curve revealed that the cutoff value of PAR was 0.039 (specificity: 0.714, sensitivity: 0.702) and area under the curve was 0.793 (95%CI: 0.735 - 0.850, P<0.001). The following variables were considered for multivariable adjustment: age, body mass index, pneumonia, aspiration, sepsis, surgery, PaO2/FiO2, red blood cell counts and PAR (P<0.01 in univariate analysis). After multivariable analysis, only age (HR: 1.033, 95%CI: 1.009 - 1.059, P=0.008), PaO2/FiO2 (HR: 0.992, 95%CI: 0.985 - 1.000, P=0.044) and PAR (HR: 4.899, 95%CI: 2.148 - 11.174, P<0.001) remained independently associated with 28-day mortality (P<0.05).ConclusionHigh PAR predicts a poor outcome in ARDS patients, therefore it appears to be a prognostic biomarker of outcomes in patients with ARDS.
Objective To investigate the expression of granulysin ( GNLY) in lung of rats with acute lung injury ( ALI) stimulated with lipopolysaccharide ( LPS) . Methods Thirty-six healthy adult Wistar rats were randomly divided into a normal control group and a LPS group, with 18 rats in each group. LPS ( 4 mg/kg) was given intraperitoneally in the LPS group to induce ALI. The same amount of normal saline was given in the control group. The rats were randomly assigned to three subgroups ( n = 6) to be sacrificed respectively at 6, 18, and 30 hours after intraperitoneal injection. Wet/dry lung weight ratio ( W/D) and pathological changes of the lung were observed. The expression of GNLY in lung tissue was assayed by immunohistochemistry. Results In the LPS group, the W/D ratio was higher than that of the control group at each time point ( P lt;0. 05) and there were a large number of inflammatory cells infiltration and edema in interstitial spaces which suggested ALI. Compared with the control group, the expression of GNLY in the LPS group was significantly increased at all time points ( P lt;0. 05) . Conclusion GNLY may participate in ALI inflammatory process, which might play a role in preventing infection induced ALI.
Objective To investigate the protective mechanism of ulinastatin（UTI） in pulmonary microvascular endothelial cells （PMVECs） attacked by serum from the patients with severe sepsis. Methods PMVECs were cultured in vitro and randomly divided into 4 groups，ie. a normal group （culture medium with 10% fetal bovine serum，group N），a health group （culture medium with 10% healthy human serum，group H），a patient group （culture medium with 10% human septic shock serum，group S），and a ulinastatin group （culture medium with 1000 U/mL UTI and 10% human septic shock serum，group U）. The proliferation activity of PMVECs was measured by MTT expressed by optical density （OD）. The concentration of TNF-α in supernatant of culture medium was examined by ELISA at 0，1，2，4，6 hours. The expression of NF-κB was examined by immunohistochemistry at 1 hour. Results Compared with group N，the cell proliferation activity of group S decreased significantly，and the cell proliferation activity of group U decreased slightly at each time poi nt. Compared with group N，the cell proliferation activity of group S and group U at 1，4，6 hours were significant different （Plt;0.05 ）. Compared with group S，the cell proliferation activity of group U at 1，2，6 hours increased significantly （Plt;0.05）. Obviously positive expression of NF-κB in PMVECs could be seen in group S，a little positive expression in group S，and no expression in group N and group H. Compared with group N，the TNF-α levels of group S and group U increased significantly at each time point with significant differences （Plt;0.01）. Compared with group S，the TNF-α levels were significantly reduced at each time point in group U （Plt;0.01）. Conclusions UTI can reduce the release of TNF-α by inhibiting NF-κB activation，thus reduce PMVECs injury attacked by serum from severe sepsis patients.
Objective To investigate the role of endothelin（ET） in lung injury during cardiopulmonary bypass （CPB） and study the possible mechanism of ET-mediated lung injury and the protective effect of ferulic acid（FA） during the procedure. Methods Twelve dogs were randomly divided into 2 groups and models of CPB with pulmonary perfusion were established by perfusion of 4 C FA solution through proximal pulmonary artery in the experiment group while control group only received 4 C crystal cardiac arrest solution without pulmonary perfusion. Changes in the content of ET, NO, malonaldehyde （MDA）, dry to wet （D/W） in lung tissue and lung function- related indices PaO2/FiO2, airway pressure （AWP）, pulmonary vascular resistance （PVR）, lung compliance before and after CPB in both groups were measured respectively. Results ET content increased after CPB in control group （P〈0. 05） ,while experiment group had a lower level of ET than that of control group （P〈0.05）; D/W, MDA levels in experiment group decreased （P〈0. 05）, but NO content increased （P〈0. 05） as compared with control group. After pulmonary perfusion with FA, PaO2/FiO2 and lung compliance values in experiment group were higher than those of control group （P〈0.05）,AWP, PVR values lowered accordingly（P〈0. 05）. Lung injury was less severe in the experiment group. Conclusion ET is involved in pathogenesis of lung injury during CPB, FA can effectively reduce lung injury and improve lung function thus having a good protective effect on the lung.
Objective To establish a rabbit model of ventilator-induced lung injury. Methods Fourty healthy New Zealand rabbits were randomly divided into 3 groups: ie. a routine 8 mL/kg tidal volume group( VT8 group) , 25 mL/kg large tidal volume group( VT25 group) , and 40 mL/kg large tidal volume group( VT40 group) . VT25 and VT40 group were further divided into 2 hours and 4 hours ventilation subgroups. Arterial blood gas, lung mechanical force and hemodynamic parameters were monitored. Lungtissue was sampled for evaluate lung wet/dry ratio and lung injury by HE stain. Bronchoalveolar lavage fluid ( BALF) was collected for measurement of protein concentration, total and differential cell counts. Results Compared with VT8 group, lung injury score in both VT40 and VT25 groups were elevated significantly, ofwhich 4 hour VT40 subgroup was the highest. Lung pathology examination of VT40 group revealed apparent alveolar deformation, interstitial and alveolar space exudation, inflammatory cells infiltration, pulmonary consolidation and alveolar hemorrhage. Lung pathology examination of VT25 group showed pulmonary intervalthickening, inflammatory cells infiltration, while alveolar intravasation was mild. Blood gas analysis showed that PaO2 /FiO2 was deteriorated with time in VT25 and VT40 groups, and PaO2 /FiO2 at the 3 hours in VT40 group( lt; 300 mm Hg) had met the acute lung injury standard, while which in VVT25 group was above 300 mmHg. Lung wet/dry ratio, BALF protein concentration, total nucleated cell and neutrophilic leukocyte were elevated in both VT25 and VT40 groups, of which 4 hours VT40 group was the highest. Conclusion Using 4 hours ventilation at a tidal volume of 40 mL/kg can successfully establish the rabbit model of ventilator-induced lung injury.