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

Saint Joseph's Translational Research Institute/Saint Joseph's Hospital of Atlanta, Atlanta, Georgia

^_* Reprint requests and correspondence: Dr. Dongming Hou, Saint Joseph's Translational Research Institute/Saint Joseph's Hospital of Atlanta, 5673 Peachtree Dunwoody Road, Suite 675, Atlanta, Georgia 30342 (Email: dhou{at}sjha.org).

Objectives: We 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.

Background: PES implantation has been shown to elicit coronary vasomotor dysfunction. However, underlying mechanisms remain largely unknown.

Methods: Nine 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.

Results: Paclitaxel-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).

Conclusions: Abnormal 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.

Key Words: endothelial function • paclitaxel-eluting stent • inflammation • oxidative stress

Abbreviations and Acronyms   BMS = bare-metal stent(s)   DES = drug-eluting stent(s)   EDdR = endothelium-dependent relaxation   EDiR = endothelium-independent relaxation   ET = endothelin   HEPES = N-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid   NO = nitric oxide   NSRS = nonstented reference segment   NTG = nitroglycerin   PES = paclitaxel-eluting stent(s)   PG = prostaglandin   RLU = relative light unit   SEM = scanning electron microscopy   SMC = smooth muscle cell   sP = substance P

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