INHIBITION OF ACUTE STENT THROMBOSIS UNDER HIGH-SHEAR FLOW CONDITIONSBY A NITRIC-OXIDE DONOR, DMHD NO AN EX-VIVO PORCINE ARTERIOVENOUS SHUNT STUDY/

Background Coronary stenting is limited by subacute thrombosis, especi ally in smaller-diameter vessels, in which shear rates are high. The o bjective of the present study was to determine whether local delivery of a new type of NO donor, the NO adduct of N,N'-dimethylhexanediamine (DMHD/NO), inhibits acute stent thrombosis (ST) at high-shear flow. M ethods and Results Effects of local infusion of DMHD/NO, intravenous a spirin, and heparin on ST were evaluated in an ex vivo porcine AV shun t model. Nitinol stents (2 mm in diameter, n=120) were placed in a tub ular chamber and perfused with blood from pigs (n=13) at a shear rate of 2100 s(-1) for 20 minutes. ST was quantified by measurement of dry thrombus weight (TW). Effects on platelet aggregation (PA), blood pres sure, bleeding time, and activated dotting time (ACT) were also examin ed. There was a dose-dependent inhibition of ST and PA by DMHD/NO. TW was reduced by 95% (1+/-2 versus 16+/-4 mg control, mean+/-SD, P<.001) , and PA was reduced by 75% (4+/-3 Versus 14+/-9 Omega/min control, P< .05) at the highest dose of 10 mu mol/L. DMHD/NO had no effects on ble eding time, ACT. or blood pressure. in contrast, aspirin (10 mg/kg), d espite inhibiting PA, had no effects on TW (12+/-5 versus 16+/-8 mg co ntrol, P=.3). Heparin (200 U/kg) reduced TW by 33% (14+/-4 versus 21+/ -3 mg control, P<.05) and prolonged ACT. Conclusions Local delivery of DMHD/NO produced a 15-fold inhibition of acute ST at high-shear flow without producing adverse systemic hemostatic or hemodynamic effects. Thus, treatment with DMHD/NO may be an effective strategy for preventi on of stent thrombosis.