The Experimental Study Of A Novel Polymer-free Sirolimus-Eluting Stent In A Porcine Model

Background: Drug-eluting stent(DES) has shown reduction in neointimal hyperplasia and restenosis.However, the long-term effect of polymer is thought to initiate and sustain inflammation and delayed endothelialization, which contribute to the occurrence of late complications, such as late in-stent thrombosis and late restenosis.And without the stimulation of polymer to the arterial wall, polymer-free DES may conquer the late complication theoretically.Objective: 1.Investigating the in vitro pharmacokinetic study and in vivo arterial sirolimus consentration. 2.To evaluate the efficacy and safty of Polymer-free sirolimus eluting-stents (PFSES) in inhibiting neointima proliferation in porcine coronary model. 3. To evaluate the efficacy and safty of the overlapping PFSES in the porcine coronary model.Methods: 1. In the in vitro pharmacokinetic study, we investigate release profile of drug from PFSES and polymer-based sirolimus-eluting stent (PSES) in the model of 37℃serum/NS solution during 28 days by the high-performance liquid chromatography(HPLC).And in the in vivo arterial drug concentration study, PFSES and PSES were implanted in the left anterior descending and lefr circumflex artery or right coronary artery.At the 14-day and 28-day after implanting, the arterial sirolimus concentration was determined by high-performance liquid chromatography/mass spectroscopy (HPLC/MS). 2 The bare metal stent (BMS), polymer-free bare metal stent (PFBMS), PSES and PFSES were implanted in left anterior descending coronary, left circumflex coronary and right coronary artery of fourty-two porcines in random. Coronary angiography and intravascular ultrasound(IVUS) were performed after 30-day ,90-day and 180-day. And after 14, 30, 90and 180-day, animals were sacrificed for histomorphologic and pathologic score analysis. 3.The overlapping PFSES and PSES were implanted in the right coronary artery of the porcine respectively in random. At the 30-day, coronary angiography and optical coherence tomography(OCT) were performed, then all animals were sacrificed for pathologic score analysis.Results: 1.In the in vitro pharmacokinetic study, approximately 90% sirolimus were released from the PFSES at 14-day, and after 28-day the concentration can not be detected, while there was about 10% sirolimus in the PSES at the same time.In the in vivo pharmacokinetic study, after 14 days, the arterial sirolimus concentration was higher in the PFSES group, and at 28-day after implanted, the concentration was similar between the PFSES and PSES group. 2.The 30-day and 90-day outcome by quantitative coronary angiography (QCA), IVUS analysis and histomorphomeric analysis showed significant reduction in luminal loss (LL) , neointima area and volume in PFSES compared with BMS; and at the 180-day, there was still the tendency of reduction in neointima proliferation. High magnification pathologic score examination revealed similar inflammation score between PFSES and BMS, both of which were lower than PSES. And at 14-day, the endothelialization of PFSES was similar to BMS, and after 30 days, PFSES group achieved complete endothelialization. 3. The 30-day outcome by QCA and OCT analysis revealed a tendency of reduction in neointima proliferation in PFSES compared with PSES in the overlapping section, while the inflammation score was lower in the PFSES group.At the 30-day, both of the two groups nearly reached complete endothelialization.Conclusion: The in vitro and in vivo pharmacokinetic study revealed the PFSES can release the siroliumus steadily and be absorbed by coronary tissue effectively. PFSES significantly reduced neointimal hyperplasia with excellent biocompatibility in porcine coronary model, even in the overlapping section.