Effects Of Lidocaine Pretreatment On Acute Lung Injury Induced By Human Gastric Juice Aspiration In Rats

Objective Aspiration of gastric contents can cause acute lung injury (ALI).Severe acute lung injury is also known as acute respiratory distress syndrome. The main clinical manifestations of ALI/ARDS are acute progressive dyspnea, hypoxia refractory to treatment, and pulmonary edema. The main pathological change of ALI/ARDS is diffuse alveolar damage.It can cause pulmonary interstitial inflammation, alveolar-capillary membrane damage, pulmonary permeability edema, pulmonary hypertension, and pulmonary micro-thrombosis. There has not been an effective strategy to treat it now. Many experiments have shown that lidocaine can inhibit the inflammatory reaction of neutrophil, inhibit excessive apoptosis and necrosis of alveolar typeⅡcells (AT-Ⅱ).The previous studies on reflu and aspiration commonly use hydrochloric acid (HCL), the main ingredients of gastric juice, to establish the animal models. And few studies used natural fasting human gastric juice. In this study, natural fasting human gastric juice was injected into the lungs to establish animal aspiration model. A certain amount of lidocaine was injected and a certain rate of lidocaine was infused continuously through the femoral vein 10 min before aspiration. The blood plasm IL-8, the lung wet to dry weight ratio (W/D), lung permeability index (LPI), total WBC and PMN/WBC in bronchoalveolar lavage fluid (BALF), arterial blood gas and pathological changes were detected to reflect the acute lung injury. The purpose of this study was to investigate the effects of lidocaine on acute lung injury (ALI) induced by human gastric juice aspiration in rats, and hope to provide help for the clinical treatment of acute lung injury.Methods In the first place, incision of trachea and paracentesis of femoral artery/vein were done in all rats. Forty SD rats of both sexes weighing 230-300g were anesthetized and randomly divided into 5 groups ( n = 8 each ):group control(C); group ALI;group L1～3 received lidocaine intravenously 3.13mg/kg bolus﹢3.13mg/kg·h infusion(concentration=0.5mg/ml), 6.25mg/kg bolus﹢6.25mg/kg·h infusion(concentration=1mg/ml), 12.5mg/kg bolus﹢12.5mg/kg·h infusion(concentration=2mg/ml) respectively 10 min before human gastric juice was instilled into the lungs ,and saline of the same volume was given intravenously in group C and group ALI.ALI was induced by intratracheal human gastric juice (PH=1.5, 0.8 ml/kg) in four groups. The control group received saline 0.8 ml/kg intratracheally. The animals were sacrificed by intraperitoneal injection of pentobarbital sodium at 6h after the induction of ALI. The lungs were immediately removed for determination of W/D weight ratio and microscopic examination. Lung permeability index (LPI) was calculated (LPI =the protein in BALF /the total protein in plasm).The number of WBC and PMN/WBC in bronchoalveolar lavage fluid (BALF) was counted. Blood plasm IL-8 concentrations at 1h and 6h after aspiration were detected, and blood gas analysis was also done at 6h after aspiration.Results⑴During the 6h of observation after aspiration, a total of 5 rats died, of which, the amount of dead rats in group ALI was 2,and 1 in group L1,L2,L3 respectively.⑵Blood plasm concentrations of IL-8 ,lung W/D weight ratio,LPI,and WBC counts ,PMN/WBC in BALF were significantly higher in group ALI, L1,L2,L3 than those in group C(P<0.05).⑶Blood plasm concentrations of IL-8,lung W/D weight ratio,LPI,WBC counts and PMN/WBC in BALF were significantly lower in group L1,L2,L3 than those in group ALI(P<0.05).No significant differences were found in the indices mentioned above among group L1,L2,L3(P>0.05).⑷There were also no significant differences in PaO2 and PaCO2 at 6h after aspiration among the five groups(P>0.05).⑸Light microscope examination: In group C, the lung tissue was intact. There was no alveolar exudate.And no edema and neutrophil infiltration was found in alveolar septum. In group ALI, alveolar wall structure was damaged severely, alveolar septum was widened, hemorrhage and infiltration of PMN was found in some alveoli of lung, and some alveoli of lung collapsed. In group L1,L2,L3,the lung tissue was not damaged or was damaged slightly. The alveolar wall had mild edema, alveolar septum thickened slightly, hemorrhage and inflammatory cell infiltration significantly reduced compared with group ALI. ALI score: The other four groups were significantly higher (P <0.05) compared with group C. Group L1,L2,L3 were significantly lower than group ALI (P <0.05). There were no significant differences among group L1,L2,L3.In conclusion, the damage to lung tissue in lidocaine pretreatment groups was ameliorated as compared with group ALI.Conclusion Pretreatment with lidocaine can attenuate ALI induced by human gastric juice aspiration. But no significant difference among group L1～3 was found in this experiment.