Effects Of Ketamine Preconditioning On Hydrochloric Acid-induced Lung Injury In Rabbits

Objective:To investigate whether ketamine can protect rabbits which were preconditioned with ketamine from hydrochloric acid-induced lung injury.Methods:Eighteen healthy male New Zealand white rabbits with clean level were anesthetized with 1%Pentobarbital sodium 3ml/kg.Mechanical ventilation was applied after completion of endotracheal intubation（VT=10ml/kg,f=50bpm,I:E=1:1,FiO₂=1.0）,1%Pentobarbital sodium and rocuronium were pumped intravenously to maintain anesthesia respectively at the rate of 5mg/kg/h and 0.1mg/kg/h while compound sodium chloride was infused at the rate of 10ml/kg/h.All animals were randomly divided into 3 groups named group C（preconditioning with saline+saline instilled）、group N（preconditioning with saline+acid instilled）and group K（preconditioning with ketamine+acid instilled）and 6 in each group.The“preconditioning with saline”was administered a volume of 5 ml/kg with normal saline,and the“preconditioning with ketamine”was administered a volume of 5 ml/kg with 0.1%ketamine within 10 minutes.The“saline instilled”was instilled intratracheally with 2 ml/kg of normal saline and the“acid instilled”was instilled intratracheally with 2 ml/kg of hydrochloric acid of pH=1.0.Heart rate and mean arterial blood pressure were recorded at T₀（immediately after endotracheal instillation）,T₁（30 minutes after endotracheal instillation）,T₂（1 hour after endotracheal instillation）,T₃（2hours after endotracheal instillation）,T₄（3 hours after endotracheal instillation）.At the same time point,arterial blood was collected for blood gas analysis to measure PaO₂,PaCO₂ and SPA and SPB in serum and oxygenation index（PaO₂/FiO₂）was calculated.Approximately 0.2 g of the left lower lobe was taken to prepare the homogenate of lung tissue,and the contents of SPA,SPB and IL-8 in the homogenate were measured by ELISA.The pathological sections of the remaining lung tissue of the left lower lobe were stained with HE for light microscopy.The pathological structure of the lung tissue was observed under the lung lesion quantitative score.The right lung lobe tissue was used to measure the wet-to-dry ratio.Results:There were no significant differences in HR and MAP between the three groups at each time point.PaO₂,PaCO₂ and oxygenation index（PaO₂/FiO₂）:Compared with group C,PaO₂ and PaO₂/FiO₂ decreased and PaCO₂ increased at T₁,T₂,T₃and T₄ in group N and group K（P<0.01）.Compared with group N,PaO₂ and PaO₂/FiO₂ in arterial blood increased and PaCO2 decreased in group K at T₃and T₄（P<0.01）.SPA and SPB:Compared with group C,the contents of SPA and SPB in serum were increased in group N and group K at T₁,T₂,T₃ and T₄（P<0.01）,and the contents of SPA and SPB in lung tissue were decreased at T₄（P<0.01）;Compared with group N,the contents of SPA and SPB in serum in group K decreased at T₃ and T₄（P<0.01）,and the contents of SPA and SPB in lung tissue increased at T₄（P<0.01）.IL-8:Compared with group C,the content of IL-8 in lung tissue in group N and group K increased（P<0.01）.Compared with group N,the content of IL-8 decreased in lung tissue in group K（P<0.01）.The lung tissue wet-to-dry ratio（W/D）and lung injury scores:Compared with the group C,the group N and the group K had higher W/D and lung injury quantitation scores（P<0.01）.Compared with the group N,the W/D and lung injury quantitation scores in group K were decreased（P<0.01）.Histopathological changes of lung:the alveolar structure was basically normal,and there were no significant pathological changes in group C;the pathological changes of lung tissue in group K were lighter than that in group N in such aspects as alveolar collapse、neutrophil accumulation in the interstitial lung and in the alveolar space and alveolar septum wideningConclusions:Preconditioning with ketamine on Hydrochloric acid-induced lung injury in rabbits can increase PaO₂ and the content of SPA and SPB in the lung tissue while can decrease PaCO₂ and the content of SPA and SPB in serum and the content of IL-8 in the lung tissue to alleviate pathological changes.Therefore,preconditioning with ketamine has a protective effects on rabbit whose lungs were injured by aspiration of hydrochloric acid.