Establishment Of The Sheep Model Of Emphysema Utilized For Bronchoscopic Lung Volume Reduction

[Objective] To establish proper animal model of heterogeneous emphysema utilized for bronchoscopic lung volume reduction by localized papain instillation and to study the pathology of the emphysematous areas in electron microscope.[Methods] 20 Sheep were treated with papain (75U/kg) delivered through a catheter positioned under bronchoscopic guidance into target area in the lung for 4 weeks. The sheep received machine positive ventilation for 15 minutes after papain instillation. Tidal volume was set 12ml/kg,rate at 12 breaths/minute and oxygen flow was 6L/minute.Artery blood gas analysis, pulmonary function and radiologic measurements were made 2weeks after the model was completed. 6 sheep were killde by intravenous injecting pentobarbital(100mg/kg). The lungs were removed, fully inflated, and the pulmonary circulation was then flushed with 2.5 L of normal saline at 20 cm H₂O pressure. Samples were collected from target tissues and normal areas to observe pathological change by light and electron microscope.[Results] Out of 20 animals,17 sheep were succeeded in generating heterogeneous emphysema and the ratio was 85%.Out of the three remaining animals,one was dead resulted in rupture of the bullae, one was dead from suffocation and pneumonia complicating empyema was in charge of the other one's death.Out of the seventeen animals,fourteen animals had no reaction to papain and three experienced couge. There was significantly difference of PO₂,PCO₂ and functional residual increment between pre- and post experiment. CT scans revealed the pulmonary markings decreased in emphysematous areas and the transparency of the areas increased. Microscopic appearance of the elnphysematous tissues showed:the alveolar wall was thinner, the alveolar ectasiaed and coalesced,elastic fibers were destroied.There were many vacuolus in typeâ…¡alveolar epithelial cells in electron microscope. Pulmonary surfactant was decreased.Apoptotic body was observed.[Conclusion] There are three features of the experiment:(1)The model of heterogeneous emphysema is more closely mimics human disease.(2)It took us shorter time to produce the model by localized instillating of papain which was stable,convenient, accurate and little infection and adverse reaction.(3) The papain which was instillated into trachea was escape the deactivation of elastase inhibitor in blood.In short,the sheep model of heterogeneous emphysema by localized instillating papain was successful and safe. It can attain requirement of the following bronchoscopic lung volume reduction. The heterogeneous emphysema was verified by CT scan and pathology.