In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 94, No. 9 ( 1996-11), p. 2228-2234
Abstract:
Background Coronary stenting is limited by subacute thrombosis, especially in smaller-diameter vessels, in which shear rates are high. The objective 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. Methods and Results Effects of local infusion of DMHD/NO, intravenous aspirin, and heparin on ST were evaluated in an ex vivo porcine AV shunt model. Nitinol stents (2 mm in diameter, n=120) were placed in a tubular 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 pressure, bleeding time, and activated clotting time (ACT) were also examined. 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 Ω/min control, P 〈 .05) at the highest dose of 10 μmol/L. DMHD/NO had no effects on bleeding time, ACT, or blood pressure. In contrast, aspirin (10 mg/kg), despite inhibiting PA, had no effects on TW (12±5 versus 16±8 mg control, 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 prevention of stent thrombosis.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.94.9.2228
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1996
detail.hit.zdb_id:
1466401-X
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