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.
Objective To investigate the effects of antithrombin-Ⅲ ( AT-Ⅲ) on the inflammatory reaction in oleic acid-induced acute lung injury ( ALI) rats. Methods Sixtymale Sprague-Dawley rats were randomly divided into five groups, ie. a normal control group, an ALI group, an AT-Ⅲ treatment group, an AT-Ⅲ +heparin treatment group, and a heparin treatment group ( n =12) . The ALI rats were induced by injecting oleic acid ( 0. 2 mL/kg) intravenously. The lung histology was scored by modified Smithtechnique. The albumin permeability of pulmonary microvascular ( Palb) was measured by single nuclide tracer technique. The extravascular lung water ( EVLW) and wet/dry weight ratio ( W/D) of lung tissues were measured by gravity way. The activity of AT-Ⅲ in plasma was determined by the method of syntheticchromogenic substrate. Tumor necrosis factor α( TNF-α) , interleukin 6 ( IL-6) and von Willebrand factor ( vWF) levels in serum were determined using commercial enzyme-linked immunosorbent assay kits. The expressions of lung tissue extacellular signal-regulated kinases ( ERK) -1 /2, P38 mitogen-activated proteinkinase ( MAPK) and c-jun N-terminal kinases ( JNK) were determined by Western blot. Results The Smith scores, EVLW, Palb , plasma level of vWF, lung tissue levels of phospho-ERK1 /2 and phospho-P38 MAPK expressions in the ALI group were all significantly higher than those in the normal control group ( P lt; 0.05) , while not significant differentwith other three treatment groups. There were not significant differences in the activity of AT-Ⅲ in plasma and phospho-JNK expression among all five groups. The serum levels of TNF-αand IL-6 in the ALI group were significantly higher than those in the normal control group and three treatment groups. Conclusions AT-Ⅲ downregulates the levels of downstreamcytokines TNF-αand IL-6,but can not inhibite the activation of ERK1 /2 and P38 MAPK, and can not relieve endothelial permeability.The study do not demonstrate the lung protective effect of AT-Ⅲ in oleic acid-induced acute lung injury.
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.