The Efficacy Of Tracheal Drug-eluting Stent On Airway Restenosis After Stent Implantation

Background and objective:Airway stenosis(AS)is caused by the compression due to the external airway lesions or airway lesions itself,which can lead to recurrent cough,wheeze,dyspnea or suffocation.The management of AS is difficult,surgical treatment is the main method,but it is not so effective for some patients,such as malignant AS,patient in poor condition.With the development of airway intervention therapy,stent implantation is considered as an effective way for tracheal stenosis[ 1,2 ].But there are some complications after stent implantation,such as stent migration,stent-related stenosis and stent fracture.Stent-related stenosis has the highest incidence.After stent implantation,granulation tissue hyperplasia can lead to stent-related stenosis[3],which limit the development of tracheal stent.The mTOR signaling pathway plays an important role in cell proliferation,apoptosis and cell cycle progression,thus blocking mTOR signaling pathway can inhibit granulation tissue hyperplasia[4].Rapamycin blocks the mTOR signaling pathway by inhibiting mTORC1.Rapamycin drug-eluting stents have been widely used in patients with coronary stenosis and achieved good clinical results[5].The rapamycin drug-eluting stents were implanted into the tracheal of rabbit model to observe the inhibitory effect of rapamycin on granulation tissue hyperplasia.Materials and methods:1.Preparation of rabbit model of airway stenosis24 healthy 4-month-old New Zealand rabbits,after anesthesia of intramuscular injection,nylon brush and anhydrous alcohol are used to scrape and destroy tracheal mucosa,the length is between 1-2cm.After 4 weeks,MSCT was used to observe the presence of stenosis and to measure it.2.Preparation of drug-eluting stentPuting the stent into the methylene chloride solution,then using the ultrasonic cleaner to remove impurities on the stent surface.Placing the stent into the rapamycin and PLGA solution.3.Effect of drug-eluting stents on restenosis after stent implantation18 rabbits(stenosis model)were divided into control group(n=6)and experimental group(n=12).All rabbits were anesthesia by intramuscular injection,and tracheal stents were implanted(8mm*20mm).The control group was implanted with nitinol uncovered stent and the experimental group was treated with rapamycin drug-eluting stent.The rabbits were sacrificed 1,2,3 month after stent implantation,then the MSCT was performed before sacrifice and the degree of tracheal stenosis was measured.Result:1.Establishment of animal model of tracheal stenosis by tracheal mucosal injuryOne rabbit suffer airway bleeding,which lead to suffocation.One rabbit died in 9th day after surgery,there is lots of white secretion in the tracheal and lots of pleural effusion in the chest,died of lung infection.Other rabbits were alive one month after surgery.The totally mortality is 8.3%,and totally survival rate is 91.7%.Four weeks after the surgery,the overall stenosis degree of trachea was 50.6%-82.8%,the mean stenosis degree was 68.7%±9.4%.The stenosis degree was graded according to the Myer-Cotton indexing.45.5%(10/22)was in grade?,54.5%(12/22)was in grade?.2.Preparation of drug-eluting stentThe satisfactory drug-eluting stent was prepared by dip coating process.After coating,the weight of stent increased.The result of SEM showed that the nitinol wire was coated drug film closely even after the distortion of the stent.3.Effect of drug-eluting stents on restenosis after stent implantationOne month after the stent implantation,there is lots of white secretion in the stent both in the experiment group and control group,the stenosis degree in the experiment group is lower than that in control group(62.3% ±1.7% vs 81.6%±2.8%),and the difference was statistically significant(P<0.05).Two months after the stent implantation,the stenosis degree in the experiment group is lower than that in one month group,and the difference was statistically significant(47.4%±6.0% vs 62.3%±1.7%,P<0.05).And the difference of the stenosis degree between two months group and three months group is not significant(50.5%±3.8% vs 47.4%±6.0%,P>0.05).Conclusion:Rapamycin drug-eluting stents can achieve the goal of inhibiting granulation tissue proliferation by slow release of the drug,which can reduce the incidence of tracheal restenosis after stent implantation.