Vascular function of bioabsorbable stented site after complete absorption of the stent

Background: Drug-eluting bioabsorbable stents (DEBSs) represent a new device-based therapy for coronary artery disease. It has been reported that the stented segment becomes re-endothelialized after 1 month and the segments proximal and distal to the stented site are functional at 2 years. In order to examine whether after complete degradation the DEBS site function was similar to the unstented segments, we performed ex vivo vasomotor function studies using pig coronary arteries. Methods: Eighteen months after implantation in the pig coronary arteries, 10 DEBS sites [four left anterior descending (LAD), four right coronary, and two left circumflex arteries] were assessed for vasomotor function using an organ chamber apparatus. They were stimulated with potassium chloride (KCl), prostaglandin2α (PGF), and three concentrations of endothelin-1 (ET). Endothelium-dependant relaxation (EDR) to substance P (SbP; 0.01–100 pM) and endothelium-independent relaxation (EIDR) to sodium nitroprusside (SNP; 0.001–10 μM) were assessed following constriction with PGF. Remaining stent segments were fixed for histologic examination. Results: DEBS sites showed rapid response to low and high concentrations of KCl, PGF, and ET. EIDR showed concentration-dependent relaxation to SNP (13.3±4.3%, 21.3±5.6%, 52.7±7.1%, 85.5±5.4%, and 100±0%). However, there was no EDR to SbP concentration-dependent stimulation. Hematoxylin/eosin and Verhoeff–Masson staining showed evidence of smooth muscle cell (SMC) migration across polymer struts, and formation of a new abluminal layer was observed. There was complete polymer strut degradation, infiltration of inflammatory cells, and minor fibrosis around some DEBS sites. Myocardial degeneration (∼1×1.5 cm) was found in the septum adjacent to the stented LAD sites (n=4). Vessel wall within the stented segment was thicker and the lumen was narrower than in the proximal and distal segments. Conclusion: During DEBS degradation period, medial SMCs migrate to the neointima developing new layers. We have demonstrated for the first time the ex vivo contraction and relaxation responses at DEBS sites to vasoactive agents after complete degradation of the stent. SMCs recovered contractile and relaxing capabilities in this segment but endothelial function was still impaired.