Study On Using Internally Medical (Minimally Invasive) Lung Volume Reduction Surgery For A Rabbit Model Of Elastase-Induced Emphysema

Background: Chronic obstructive pulmonary disease (COPD) is a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States and is projected to rank fifth in 2020 as a worldwide burden of disease. There is a high incidence (3.17%) of COPD in northern and mid China, from a investigation of 0.1 million adults. Up to now, there are no special medical treatments to deal with COPD and the therapeutic effects are unsatisfactory, especially the end-stage. In 1995, following Brantigan, Cooper reused and improved lung volume reduction surgery (LVRS) to treat with COPD, which resulted in dramatic curative effect in the near future. However, strict indication and contraindication limit the clinical use of LVRS, in addition to more postoperative complications and higher costs. Thus, the increasing awareness is to extend operation indication, diminish complications and mortality, and cut down the costs. Objective: To study the possibility, effectiveness and reliability of usinginternally medical (minimally invasive) lung volume reduction surgery to treat a rabbit model of elastase-induced emphysema. And to provide the clinical application of internally medical (minimally invasive) lung volume reduction surgery with experimental basis.Methods: 20 Male New Zealand white rabbits were used for these studies and randomized to surgery group (n=10) vs. control sham surgery group (n=10). Animals were induced to emphysema by injecting pancreatic elastase into trachea only once. A micro-tube (ID=0.5 mm) was catheterized into the middle or inferior lobe segments of right lung of all rabbits under X-ray. The fibrin-based sealant (0.5ml) was injected into the segmental bronchi of every surgery group rabbit through the end hole of the catheter resulting in segmental atelectasis. The rabbits of control sham surgery group were injected with normal sodium. Lung function testing and blood gas analysis were performed at baseline before induction of emphysema, at week 6 immediately preoperatively (after induction of emphysema), and 2 week after the operation. All treated animals were monitored for hypoxemia, dyspnoea, pulmonary infection, fever, weight loss, and failure to eat or drink appropriately.Results: Moderate emphysema developed after elastase injection, assessed by lung function, blood gas analysis and postmortem histology. There was no significant difference between two groups at baseline and at week 6 immediately preoperatively. Following internally medical(minimally invasive) lung volume reduction surgery, function residual capacity decreased [(35.31±2.88)ml vs.(42.91±5.06)ml, P < 0.01] and FEV0.4/FVC increased [(82.11±2.94)% vs.(70.27±4.46)%, P< 0.01]. PaO₂ [(93.44±6.43)mmHg vs.(76.44±6.60)mmHg, P < 0.01] and SaO₂ [(96.78±1.09)% vs.(93.89±1.97) %, P < 0.01] also improved significantly, and histopathology demonstrated that surgery caused collapse of lung with focal scarring and collagen deposition. Pulmonary atelectasis was seen under X-ray with the area of 20%³0%. There were no changes in control sham animals. Except one rabbit of surgery died of pulmonary infection, there were no other complications observed after surgery. Conclusion: This pilot study suggests that lung volume reduction can be achieved in animals effectively and safely using internally medical (minimally invasive) approach. It has the potential for simplifying volume reduction, extending indications, and reducing morbidity, mortality, and costs in humans. Further research including clinic research is required to access long-term effects and complications of this method.