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Animal Study on Bronchoscopic Lung Volume Reduction Using Tissue Sealant

Author: LiaoXiaoBin
Tutor: YangHePing
School: Third Military Medical University
Course: Internal Medicine
Keywords: brobronchoscopic lung volume reduction tissue sealant tetracycline balloon crossbreed dog operation
CLC: R563.3
Type: Master's thesis
Year: 2008
Downloads: 49
Quote: 1
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Abstract

Emphysema is 4a debilitating lung disease continuing to be a major source of morbidity and mortality in the developed countries. Estimates suggest that as many as two million people are affected in the United States. Lung volume reduction surgery (LVRS) can relieve dyspnea in their COPD patients by correcting the overinflation of the chest by surgically removing lung tissue.Patients with advanced chronic obstructive pulmonary disease (COPD) continue to experience exertional breathlessness despite optimum medical therapy. In selected patients, lung volume reduction surgery (LVRS) has been shown to improve exercise capacity and quality of life . LVRS, however, is not without risk. In particular, the National Emphysema Treatment Trial (NETT) found an excess mortality (16% at 30 days) in patients with the most severe disease. Even when highrisk patients were excluded, surgical volume reduction has been associated with significant morbidity and an early mortality rate of about 5% .For this reason, there is a need for safer alternatives. Bronchoscopic lung volume reduction (BLVR) has the potential to become such an alternative. BLVR involves placing a device to obstruct the airway(s) leading to the most hyperinflated, emphysematous parts of the lung. The rationale for this approach is that endobronchial obstruction should cause these areas to collapse and thus, by reducing hyperinflation, alleviate symptoms without recourse to surgery.Devices and techniques under study include one-way bronchial valves inserted via fiberoptic bronchoscopy to promote atelectasis in emphysematous lung, promotion of focal atelectasis and fibrosis by bronchoscopic injection of polymers into emphysematous regions of lung, bronchopulmonary fenestrations to enhance expiratory flow, and thoracoscopic plication or compression of emphysematous lung. The goal of all of these procedures is to replicate the benefit of LVRS without the trauma, risks, and extended recovery of open LVRS. Refinement and application of these techniques will allow patients with emphysema and their physicians and surgeons to choose from a number of viable options for lung volume reduction.It may prove to be the existing case that valve insertion will be the appropriate therapy when there is heterogeneous disease and a target lobe can be identified. In homogeneous disease, with intralobar collateral ventilation being more likely, the airway bypass approach may prove to be preferable. Only animal data about bronchoscopic injection of polymers are available at present and it remains unclear whether it will be possible to apply this technique to humans. It is possible that this technique could be used in both types disease.The approach of bronchoscopic injection of polymers has been to find tissue engineering approaches that will produce lung volume reduction by causing scarring in target areas of the lung . Only animal data are available at present and it remains unclear whether it will be possible to apply this technique to humans. Ingenito et al. suggested collapsing target regions of the lungs using a procedure similar to bronchoalveolar lavage. The lavage involves controlled removal of bronchial epithelial lining cells with a washout solution and the deployment of a fibrin hydrogel. In a sheep model of emphysema this procedure achieved scar tissue formation, which replaced hyperinflated lung, reduced overall lung volume, and improved respiratory function safely and consistently.In our study, we observe the lung shape of crossbreed dogs, investigates the possibility of lung volume reduction with bronchoscope, explore the method and technique of BLVR, observe the effect of bronchoscopic lung volume reduction using fibrin-based glue,investigate the possibility and safe, offer experimental evidence of the minimally invasive techniques for the treatment of emphysema.The main contents of our study are as follows:1. To observe the lung shape of crossbreed dogs and investigate the possibility of lung volume reduction with brobronchoscope1) To investigate general state of health,at baseline, at operation of BLVR,at recovery after BLVR, including heart rate, respiratory rate, oxygen saturation.2) To observe the lung shape of crossbreed dogs including the length of trachea by brobronchoscope.3) To observe the dissection of lung after autopsy and compare with the lung shape observed by brobronchoscope.2. Animal study on bronchoscopic lung volume reduction using tetracycline1) To explore the method and technique of injecting tetracycline into treated sites by bronchoscope.2) To detected target lung by roentgenographic examination and histopathological methods at baseline,at 4w、8w and 12w postoperation respectively, and the present of TypeⅠcollagen,TypeⅡcollagen .3. Animal study on bronchoscopic lung volume reduction using tissue sealant.1) To observe the glutinosity and biocompatibility of tissue sealant.2) To explore the method and technique of injecting tissue sealant into treated sites by bronchoscope.3) To detected target lung by roentgenographic examination and histopathological methods at baseline,at 1h、4w and 8w postoperation respectively, and the present of TypeⅠcollagen,TypeⅡcollagen .Main results1. Procedure of operation was successful without technic difficulty, there were not dead animals, and complications did not happen.2. The lung shape of crossbreed dogs observed by brobronchoscope suggested that crossbreed dog was suitable for the operation of fibrobronchoscope.3. Serial CT scans, Autopsy and Microscopic examination to target lung performed 12w after BLVR using tetracycline, showed scar tissue substitute target lung and complications did not happen. Obviously and persistent cough happened after BLVR in the dogs explained that tetracycline were stimulant .4. Fibrin glue and 0.1% poly-l-lysine are choosed as tissue sealant injecting into treated sites, and were found satisfactory glutinosity and biocompatibility.5. Serial CT scans, Autopsy and Microscopic examination to target lung performed 8w after BLVR using tissue sealant, showed scar tissue substitute target lung and complications did not happen. Obviously and persistent cough did not happened after BLVR in the dogs explained that tissue sealant were mild.6. Tissue sealant was more suitable than tetracycline in BLVR. Because scar formation depend on satisfactory glutinosity and biocompatibility of tissue sealant in BLVR using tissue sealant, and scar formation was by inflammation in BLVR using tetracycline, the injury suffered from tetracycline was visible.conclusion:1. Operative procedure through BLVR is easy, trauma is little, complications are few, and this method will be used in lung volume reduction.2. Fibrin glue and 0.1% poly-l-lysine are choosed as tissue sealant because of it,s satisfactory glutinosity and biocompatibility.3. BLVR using tissue sealant demonstrates it can reduce lung volume by promoting localized fibroblast proliferation, collagen synthesis, and scar formation achieved,so it provides an effective, safer alternative to LVRS.

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CLC: > Medicine, health > Internal Medicine > Respiratory system and chest diseases > Pulmonary disease > Emphysema
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