Characterization of Vascular Injury Responses to Stent Insertion in an Ex-vivo Arterial Perfusion Model

Abstract

Purpose To develop an ex-vivo arterial perfusion model to evaluate vascular responses to bare metal stents (BMS) and drug-eluting stents (DES) in porcine carotid arteries. Materials and Methods Porcine carotid arteries with BMS or DES were cultured under hemodynamic stimuli for 24 hours and 72 hours. Vascular responses of arteries with stents were assessed by cellular functionality and gene expression and compared with a noninjured (NI) control group at each time point. Cellular functionality was confirmed with sequential dosing of norepinephrine (NE), acetylcholine (ACH), and sodium nitroprusside (SNP). QuantiGene (Panomics, Fremont, California) branched DNA (bDNA) assay was used to evaluate gene expression of endothelial cell (EC) and smooth muscle cell (SMC) biomarkers and compare it with responses of in-vivo arteries with stents. Bromodeoxyuridine (BrDU) stain was also used to detect cellular proliferation in the ex-vivo arteries with stents. Results EC relaxation and SMC contraction in response to vasoactivators indicated the arteries remained viable and functional for at least 72 hours in culture. SMC-dependent contractility and EC-dependent relaxation were lower in arteries with stents compared with NI arteries. Greater SMC proliferation was observed in BMS arteries compared with DES arteries. Cellular proliferation, EC function, and SMC marker expression at acute time points were similar between both models suggesting that the ex-vivo arterial model can provide comparative predictions of stent injury in vivo. Conclusions The ex-vivo arterial perfusion model can be used as a quick and less costly (than current in-vivo and some in-vitro perfusion testing models) approach for evaluating the vascular responses to various stent design parameters (eg, strut thickness, strut width).