Lung Ultrasound Quantitatively Evaluates Extravascular Lung Water Content And Related Mechanisms Research

Background:Extravascular lung water increase is one of the pathological basis of common lung diseases in adults,children and newborns.Extravascular lung water refers to the accumulation of intrapulmonary fluid outside the pulmonary blood vessels,mainly in the interstitial and alveolar spaces,which clinically manifests as pulmonary edema.Lung fluid accumulation can cause respiratory failure.At present,extravascular pulmonary water can be evaluated clinically by various methods,but each has its own disadvantages.With the development of pulmonary ultrasound technology,pulmonary ultrasound is used to diagnose pulmonary edema and to quantitatively evaluate extravascular lung water.At the same time,lung ultrasound can be used to determine lung pathological changes.Based on the image characteristics of lung ultrasound and clinical observations,we tried to find a strategy suitable for quantitative extravascular lung water evaluation in newborns.In addition,Pulmonary ultrasound was used to dynamically monitor the change of ultrasound images of extravascular lung water over time and explore its underlying mechanism.Methods:In this study,an animal model was established by injecting different volume of normal saline into the lungs of New Zealand Rabbits through tracheal intubation,and the performance of different levels of extravascular lung water on lung ultrasound was investigated.Through our pre-set B-line scoring system and different models of extravascular lung water content to study the correlation between the quantitative ultrasound scores and extravascular lung water,and the effects of different extravascular lung water on the respiratory system.At the same time,combined with clinical observations,lung ultrasound was used to monitor changes in ultrasound images of New Zealand Rabbits during the 4 hours after injecting different volume of normal saline into the lungs.The correlation between ultrasound images and pathological changes was studied by histopathological analysis.qRT-PCR,Western Blot,and immunohistochemical methods were used to detect the effects of different levels of extravascular lung water on the expression of pulmonary surfactant B and pulmonary surfactant C,and aquaporin 1 and Na,K-ATPase proteins in the lung.Results:As the amount of normal saline injected into the lungs increased,the ultrasound B-line score increased,and respiratory distress worsened.The B-line score had significant statistical correlation with lung wet/dry ratio(r2=0.946)and PaO2/FiO2 ratio(r2=0.916).In addition,the results suggest that B-line score had favorable intraobserver and interobserver reproducibility.When the volume of normal saline injected into the lung was ?4ml/kg,lung ultrasound showed that most of the extravascular lung water was absorbed after 4 hours.When the volume of injected saline was?6ml/kg,some areas of pulmonary edema appear as consolidation of the lungs.qRT-PCR and Western blot results showed that the mRNA and protein expression of pulmonary surfactant protein B and pulmonary surfactant protein C were significantly down-regulated(P<0.05).At the same time,the mRNA and protein expression levels of aquaporin 1 and Na,K-ATPase were significantly reduced.Immunohistochemical staining showed the same results.Conclusions:This study shows that the B-line score can be used as a sensitive,quantitative,non-invasive,real-time indicator for evaluating extravascular lung water increase.The B-line score has significant correlation with the results of lung weight.In addition,the B-line score can also predict lung oxygenation status.Clinically,it can guide fluid management and respiratory support strategy.With the increase of extravascular lung water,the pulmonary ultrasound image changed from pulmonary edema to pulmonary consolidation after 4 hours,and its underlying mechanism was related to the significant down-regulation of lung surface protein expression.It can guide the administration of exogenous pulmonary surfactant in clinical settings.At the same time,with the increase of extravascular lung water,the protein expressions of aquaporin 1 and Na,K-ATPase were significantly down-regulated after 4 hours,which may cause clearance dysfunction of alveolar fluid.Aggravate lung injury.