| BackgroundChronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by inreversible limited air flow, It caused high mortality, mobidity and disability, COPD has lead to direct and indirect huge medical burden to both the families and society in the world.Emphysema is the main pathological types of COPD. In all stages of COPD, there is gas tripping in the lungs, which increasing lung residual volume and presented as dyspnea and short of breath especially when exercise. The drug therapy in patients with severe emphysema is not so effects. The NETT (National emphysema treatment trial) result shows lung volume reduction surgery (LVRS) are able to improve the patients'symptom, the quality of life and survival. In recent years, Bronchoscopic lung volume reduction (BLVR) has been paid much attention by physicians since its minimally invasive, safety and similar out comes with LVRS. So far, there are a few products has been used successfully in clinic trials outside of the countries. However, we have not see a research paper published in China about implant one- way valves directly through the bronchoscopy's channel.ObjectiveTo evaluate the safety and effectivity of the self-made one-way valve which can be implanted in the target bronchi through the channel of bronchoscope.Laboratory animals:In this study, we use twelve healthy male goats of 12 to 18-month-old (provided by Animal Center of People's Liberation Army General Hospital), weighing 16 ~ 24 kg.MaterialOne-way valves are designed and manufactured by the 306th Hospital of PLA and Beijing Puyishengji Science and Technology Co.,Ltd. It is made of 316L stainless steel, nickel titanium alloy wire and polyurethane gel. Caliper of bronchial diameter and the equipment of implanting are provided by Puyishengji Science and Technology Co.,Ltd Beijing.MethodsExperimental goats have been fasting for 72 h before operation, use 3% pentobarbital sodium 0.7 ml/ kg intravenous injection to anaesthetize. 8.5 or 9 tracheal tubes were put in through mouth, draw the arterial blood from ear artery of goats for arterial blood-gas analysis before the operation, and 3.2 million U of sodium penicillin intravenous drip during intraoperation.We choose right lung dorsal 3 ~ 4 ranks-bronchium as the target lungs, put the bronchial diameter measuring instrument through biopsy channel and observe and measure caliber of the target bronchium on screen of bronchoscope, select the suitable valves from FM4 to FM8 (diameter from 4mm to 8mm), fix the one way valves to the conveyer system with metal top of valve on screws, and put them into sheath tube together with the push rod. The holder of bronchoscope cooperates with operator to implant valve conveyer system into target bronchium through biopsy channel under the direct vision. And counterclockwisely rotate push rod to release valves after positioning the system appropriately. Each goat was implanted three valves. At the same time, the operator observe the valve position and working state, and make sure the valve steadily and in a stable working condition: keep open when expiration, close when inspiration. There are 3 of the valves at unsatisfactory location at the beginning. They were taken out by bronchoscope biopsy forceps and re-implanted. After operation, the location and number of valves were checked by X-ray transillumination. 30 minutes after the procedure, arterial blood gas analysis was test again. The goats were given intramuscular injection of amikacin 0.2g once a day for three days after operation, At the time point of 2, 4, 8, 12 weeks after the operation, the experimental goats were tested arterial blood gas analysis and chest CT scan under the intravenous anesthesia (method same as above). At each four time points, three goats were killed painless bleeding under anesthesia. Then, do thoracotomy immediately to resect the whole lung as the samples and observed them in the gross. The bronchial wall around the valves, the target lung and the normal left lung tissue were slice up, the later are observed as the normal control. All slices were HE stain. The pathological manifestations including valves themself injury to bronchial walls, alveolar collapses and the other representation, such as any infection, ulcer and so on. Results(1) 36 valves were implanted successfully. 12 goats were well toleranced. No dyspnea and short of breath were observed during and after the procedure .One goat take less food than before, the temperature is higher than the baseline, but there was no significant change in respiratory rate, and fully recovered one week later. There were no pneumothorax occurred, no goat died unexpected in this animals study.(2) Result of arterial blood gas analysis: Except the 30 min data, the arterial blood gas datas did not have significant changes in all other time points.(3)Imaging Results: X-ray transillumination was done shortly after the procedure. One valve was coughed out on the operating table, since the valve's caliber is too small. Other valves remained in normal location. At the end of the experiment totally three valves was missing. Postoperative CT scan showed that 15/33 (45%) of the target lungs collapse and deteleotasis more or less, little fibrosis can be seen in the target lungs in some animals.There was no imaging showed pneumothorax, obstructive pneumonia, abscess and so on.(4)Histopathological findings: In the gross, there were visible scars contractures-like changes on the surface of some lungs. Valves were fixed well, close to bronchial mucosa, and bronchial mucosa surface was smooth without ulceration. We can see sputum adhesion around six valves (6/33) and distal lung tissue collapsed in varying degrees. A little fibrous tissue filled around the valves at 12 weeks. It is a little bit difficulty to separate the valves from the bronchus. HE staining slices showed that bronchus mucosa of peripheral of valve was become thicken, and distal lung tissue of the valves collapse and alveolar space become small and narrow. There are a few lymphocytes and mononuclear cells infiltrated in interstitial lung tissues, and a little fibrous tissue hyperplasia can been seen. But there was no lung tissue necrosis or abscess. The valves were smooth and flexible without deformation when cleaning-up and removed. In the lungs which were killed at 12 weeks, a little cellulose attached to the surface of some valves.Though it's difficult to peel off, but there is no deformation and damage of valve and valve is integrity.Conclusion(1) The One-way valve which were adopted in this experiment, are designed independently, the valves are made of endovascular stent materials. It can be directly implanted in the target bronchus through a bronchoscopy's biopsy channel. The procedure can be as easy as Emphasys's valves. The operators can see if the valves is in the accurately position or not when performance. The compatibility with human tissue is well. The result shows that the self-made valve is secure and effective. Moreover, there are more size can be choose. However, the membrane of one-way valve isn't as sensitive and exquisite as the foreign same kind of products.(2) CT scan showed that there were some grads of lung tissues collapse or atelectasis in nearly half of taget lungs at two weeks time point. But there were no extension lung tissues collapse at 12 weeks.(3) There are hyperplasia of the fibrous-like substance, which make the valve stick to the bronchial mucous membrane firmly and difficult to peel off at 12 weeks after the procedure. It indicated that if you need to take out the valve, it should be done within one to two monthes after the procedrue.(4) The results of this study support the routine use of antibiotics 3 ~ 5 days to prevent pneumonia. The applications of the expectorant drug can facilitately expectorate the sputums and phlegm.(5) It is a kind of minimal intervention technique with no severe postoperative complications, such as pneumothorax, pneumonia and no death in this experiment. The valves had good histocompatibility.(6) The one-way valve used in this experiment was independently designed and manufactured. It has showed the characteristic of good security, easy to procedrue and much cheaper than import products. It also showed a lung volum reduction outcome. We expecte the COPD patients with severe emphysema can get benefits from it in the near future. |
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