Abstract 4344: Attenuated Vasoconstrictor Responses to Coronary Arterial Aspirate From Patients With Paclitaxel Eluting Stent versus Bare Metal Stent Implantation for Saphenous Vein Aortocoronary Bypass Stenosis
Arterial aspirate retrieved from saphenous vein aortocoronary bypass grafts during implantation of bare metal stents (BMS) induces vasoconstriction through serotonin and thromboxane A2. Drug eluting stents (paclitaxel eluting stents, PES) chronically impair endothelium-dependent coronary vasomotion in patients. We now addressed the acute effects of aspirate from PES on norepinephrine-induced vasoconstriction. Using a distal balloon protection/aspiration device, coronary arterial blood was retrieved during stent implantation in patients with a severe saphenous vein aortocoronary bypass stenosis (75±4%) (n=12 BMS; n=13 PES). Using a bioassay of rat mesenteric arteries, vasomotion was tested in response to the aspirate. A concentration response curve of norepinephrine (0 – 3*10−5M) was obtained on top of paclitaxel (3nM for 1min) or buffer, respectively. To address microtubular stabilization by paclitaxel, thin aterial sections were used for immunofluorescent tubulin staining. Aspirate plasma before stent implantation constricted arteries, with (+E) and without (−E) intact endothelium and irrespective of the stent used (+E: 53±9 PES and 56±9 BMS; −E: 95±11 PES and 94±25 BMS; vasoconstriction in Δ force normalized to maximum contraction with KCl [% KClmax], each). No change of aspirate induced vasoconstriction was detected after BMS implantation (+E: 63±23; −E: 89±40). With PES, the vasoconstriction was significantly less (+E: 11±6; −E: 21±7). Low nanomolar concentrations of paclitaxel resulted in a significant shift to the right of the concentration-response curve to norepinephrine (EC50 1.14*10−6M vs 2.1*10−6M). Immunofluorescence micrographs showed a significant microtubule condensation in arteries incubated with aspirate from PMS implantation (9.5±3.1a.u. vs untreated controls 0.5±4.1a.u.). In conclusion, aspirate from PES implantation attenuates acute vasoconstriction, possibly by aterial microtubule stabilization with paclitaxel.