| Emphysema is a character of chronic obstructive pulmonary disease(COPD),which mainly causes dyspnea. Bronchoscopic lung volume reduction(BLVR) isbased on the bronchoscopic apporch to implant suitable intra-bronchi valves inpulmonary segments or subsegments of emphysema. The rationale for this wasthat the valve would be necessary for the venting of air to achieve iatrogenicatelectasis, as well as for the clearance of secretions, prevention of infections.Objective: 1. Observing change of vital signs and incidence of complications afterbronchiscopic lung volume reduction(BLVR). Investigating the safety andfeasibility of BLVR. 2. Investigating therapeutic efficacy of BLVR by comparingchange of residual volume pro-operation to afer-operation and observingpulmonary collapse after BLVR. 3. Observing injury of airway around stentsduring variable times after implanting stents in a health sheep. Investigating thetoleration of the stents.Methods: 14 6-month female sheep (weight: 20～30kg) were distributed into twoparts. Models for advanced heterogeneous emphysema was developed in 13 sheep.Under general anesthesia, the sheep were treated with papain (75 U/kg weekly for4 weeks) delivered through a catheter positioned under bronchoscopic guidanceinto local segment areas of right lower lober and were mechanically ventilated for20 minutes to generate heterogeneous emphysema, which were definited by CTscans. After target area was located by CT scans, the models were intubed andmechanically ventilated. Secondary, Target bronchus was located by X-rayvisualization and 1～2 suitable one-way flap stents were delivered to targetsubsegment bronchus by a guide wire and delivery system under bronchoscopicguidance. The sheep was treated with penicillinum for three day after operation. Change of functional residual capacity (FRC) was analyzed before and 8 weekspost-BLVR. After completion of 8-week post-BLVR physiologic measurements,the animals were killed with intravenous pentobarbital (100 mg/kg) and autopsied.Sites of BLVR were readily detected by visual inspection and manual palpation.The lungs were sliced serially into 2 to 2.5cm axial sections and further inspectedfor signs of scar formation or other gross changes. Samples from all BLVRtreatment sites and representative samples from untreated sites were fixed in 10%buffered formalin and inspected by light microscope. Samples were collected fromairway around stents to observe ultramicro-pathologic change of bronchi. Theother health sheep was implanted a few stents by same method during variabletimes(2 months, 4months, 6months after primary operation). After all operations,the sheep was euthanized. Samples were collected from bronchi of variable timesto observe degree of injury of stents to bronchi by light and electron microscope.Result: 1. Nine models were successfully implanted 15 stents, one of whichwas expectorated because of unsuitable stent. Other 4 were dead from suffocationbecause of vomiting. The health sheep was implants 9 stents. The rate ofsuccessful procedure was 95.8%(23 of 24). 2. BLVR was well tolerated. Thevital signs of the animals were stable during operations. Moreover, The animalscould eat and walk one hour after operation. None of the animals developedhypoxemia, hemoptysis, bronchospasm, or respiratory distress either during orafter treatment. 3. There were not hemorrhea or shock during operations. Theoperative procedure was simple and feasible. The combination of CT scan andX-opacification makes target sites more accurable. 4. Serial CT scans providedvisual documentation of the changes produced by BLVR treatment. At basic beforeBLVR the target area selected for treatment showed no abnormal densities. At 8weeks after BLVR, collapse and loss of volume are demonstrated at the treatmentsite. 5. Postoperative increment of FRC reduced. Oxygen partial pressure and O2saturation were decreased, which may be caused by development of emphysema. 6.Gross and microscopic examination of the lungs revealed that there werepulmonary collapse in lung segments distal to bracket 8 weeks after BLVR. There was no suggestion of pneumonitis, granuloma and abscess formation around stentts.7. The injury of stents to bronchi was slight 8 weeks after BLVR. Two samplesrevealed small amounts of fibroblasts, smooth muscle and tunica mucosabronchirum epithelial hyperplasia, 7 cases did not reveal obvious abnormality.Microscopic examination of bronchi around stents revealed fibroblasts hyperplasy,tunica mucosa bronchirum and submucous membrane with indentation thinnedand cartilagines tracheales were no destructure 2 months after BLVR. After 4months, There were connective tissues around stents. There were tunica mucosabronchirum epithelial squamous metaplasia. Lymphocytes and plasmocytes wereinfiltrated in sub-mucous membrance. Smooth muscles focus hyperplasied. Therewere no fibroblasts proliferation. After 6 months, the tunica mucosa bronchirumepitheliums were injured. Lymphocytes and plasmocytes were infiltrated insub-mucous membrance. Local fibroblasts proliferated and smooth muscles wereatrophy and disappeared. However, Electron microscopic examination revealedthat the arrangement of tunica mucosa tracheae epithelium was well. Ciliatedepithelial cells swelled and cellular nucleus were large. Plastiosome wasdegenerated and cilium on free end were scarce. There were many dilated roughendoplasmic reticulum in goblet cells, which contained moderated dense matrixand few ribosomes.Conclusion: 1. The model of heterogeneous emphysema is more closely mimicshuman disease, therefore, these model will contributed to basic research ofemphysema. 2. Bronchoscopic lung volume reduction using one-way flap bracketis a minimally invasive procedure and the stimulus of the brackets to walls ofbronchi is slight. 3. The technique may attain effectiveness of surgery. Therefore itmay be a perspective treatment. 4. The long-term curative effect and impairmentof the brackets to walls of bronchi need further study for the reason that ourobserved time was only 8 weeks. |
