Endothelium-dependent vasomotor dysfunction in pig coronary arteries with Paclitaxel-eluting stents is associated with inflammation and oxidative stress.
OBJECTIVE
We sought to evaluate coronary epicardial and intramyocardial resistance, arterial vasomotor function, local inflammatory reaction, and superoxide anion (O(2)(.-)) 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 O(2)(*-) 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 (>or=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 O(2)(*-) production at both proximal and distal nonstented coronary reference segments was elevated for PES when compared with O(2)(*-) 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.
Pendyala
Lakshmana K
LK
Saint Joseph's Translational Research Institute/Saint Joseph's Hospital of Atlanta, Atlanta, Georgia 30342, USA.
Li
Jinsheng
J
Shinke
Toshiro
T
Geva
Sarah
S
Yin
Xinhua
X
Chen
Jack P
JP
King
Spencer B
SB
Robinson
Keith A
KA
Chronos
Nicolas A F
NA
Hou
Dongming
D
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D003331:Coronary Vessels / Q000293:injuries / Q000503:physiopathology*; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000293:injuries / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced* / Q000209:etiology; D018384:Oxidative Stress; D017239:Paclitaxel / Q000009:adverse effects*; D013552:Swine
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel