Abstract 414: Endothelial dysfunction of Epicardial Resistance Arteries in Pigs after Coronary Artery Implant of Paclitaxel-Eluting Stents

Background: Abnormal endothelium-dependent vasorelaxation of coronary arteries adjacent to drug-eluting stent (DES) implants has been reported and may be associated with late stent thrombosis. However, epicardial resistance vessel vasomotor function in the distal perfusion bed of DES has not been studied. We tested small vessel function 1 mo after coronary artery paclitaxel-eluting stent (PES) implant. Methods: Pigs (n=9) received overlapping bare metal stent (BMS) and PES as well as naïve vessels. One month later, myocardium distal to the stented region, as well as similar location in non-stented vessel (nSV) was harvested. Eighteen epicardial resistance arteries (lumen diameter ~ 250μm) were isolated under a dissecting microscope and mounted on a myograph apparatus. Vasoconstriction (KCl, PGF2α & ET-1), endothelial-dependent relaxation (EDdR) response to substance P (SP), and endothelial-independent relaxation (EDiR) to sodium nitroprosside (SNP) were measured. Results: Angiographic late lumen loss at 1-mo was less for PES than BMS (p=0.002). Epicardial resistance artery relaxation was attenuated in the perfusion distribution of PES, as maximal EDdR in response to SP was 56.0±7.0% compared to vessels isolated from the perfusion distribution of BMS (85.0±7.0%) and non-stented coronary segments (107±2.0%, P=0.034 vs. PES). Maximal EDiR in response to SNP, however, was similar among the groups (90.0±6.0%, PES; 98.0±2.0%, BMS; 123±5.0%, nSV; P=NS respectively). Similarly contraction to endothelin-1 was not affected by stent type (3.95±0.56%, PES; 3.07±0.65%, BMS; 3.01±0.36%, nSV; ratio of contraction ET-1/KCl; P=NS respectively). Conclusions: Epicardial resistance artery endothelial-dependent vasomotor dysfunction is present one month after overlapping coronary PES implant in swine. Derangement of microcirculatory vasomotor function may also be present with DES implant in humans and be associated with a spectrum of adverse clinical sequelae.