Endothelium-Dependent Vasomotor Dysfunction in Pig Coronary Arteries With Paclitaxel-Eluting Stents Is Associated With Inflammation and Oxidative Stress

ObjectivesWe sought to evaluate coronary epicardial and intramyocardial resistance, arterial vasomotor function, local inflammatory reaction, and superoxide anion (O2· −) production after overlapping paclitaxel-eluting stent (PES) implantation in a porcine model.BackgroundPES implantation has been shown to elicit coronary vasomotor dysfunction. However, underlying mechanisms remain largely unknown.MethodsNine pigs received overlapping PES and bare-metal stents (BMS) in the coronary arteries, and 3 sham animals were naïve. At 1 month, inflammatory response at the overlapped region was assessed by histopathology and scanning electron microscopy. Endothelial vasomotor function and O2· − at nonstented coronary reference segments were measured by angiography and organ chamber tensiometry, and lucigenin luminometry; vasomotor function of distal resistance arteries was measured by myography.ResultsPaclitaxel-eluting stents showed reduced late lumen loss, but inflammation and luminal inflammatory cell adherence were higher than for BMS (p < 0.001) at overlapped segments. Endothelium-dependent relaxation to substance P was significantly impaired in PES at nonstented coronary reference segments (≥15 mm proximally and distally) and perfusion bed resistance arteries (p < 0.05). In contrast, endothelium-independent relaxation to nitroglycerin and sodium-nitroprusside was similar between groups. Local O2· − production at both proximal and distal nonstented coronary reference segments was elevated for PES when compared with O2· − production in BMS and naïve arteries (p < 0.001).ConclusionsAbnormal endothelium-dependent relaxation at both coronary conduit and resistance arteries was demonstrated after overlapping PES implantation. Profound localized inflammatory reaction, as well as enhanced local oxidative stress, may contribute to vasomotor dysfunction.