Abstract 3930: Paclitaxel-Eluting Stent Induces Endothelial Dysfunction Associated with Local Oxidative Stress in Pig Coronary Model
Background: Paclitaxel-eluting stents (PES) appears to elicit epicardial artery vasomotor dysfunction. However, the mechanism is not yet known. We evaluated endothelial function and local superoxide anion production after PES implantation.
Methods: Pigs (n=9) received overlapping PES and bare metal stents (BMS). Coronary vasomotor function proximal and distal (≥15mm) to the stents was measured angiographically in-vivo and on harvested tissue in-vitro in an organ chamber apparatus 1-mo post-implant, and superoxide (O2−) production of adjacent segments was estimated by lucigenin chemiluminescence.
Results: In-vivo, angiographic %diameter change following intracoronary (IC) endothelium-dependent relaxation (EDdR) substance P (sP, 2ng/kg) was diminished in PES (pro 0±6 %, dis 0±9%) compared to BMS (pro 10±6%, dis 10±7%; P<0.05) and naíve (pro 15±8 %, dist 15±10 %; P<0.05). But, endothelium-independent relaxation (EdiR) response to NTG (IC, 200μg) was not different between the two stent types. Similarly, in-vitro organ chamber revealed that EDdR response to sP and A23187 in both proximal and distal segments was significantly impaired in PES vs. BMS and naive (p<0.001), but EdiR to SNP was preserved (P=NS). O.2− production was higher proximal and distal to PES than BMS and naíve (36.2±6.5 vs.14.6±3.2 and 12.2±1.7 RLU/s/mg tissue, P<0.001 and 77.2±8 vs. 23.3±5.4, and 19.4±0.9 RLU/s/mg tissue, P<0.001).
Conclusions: A profound adverse effect of PES on endothelium-dependent vasomotor relaxation in conduit vessel segments both proximal and distal to overlapping implants, was observed both in-vivo and in-vitro, associated with local enhancement of oxidative stress.