Inhibition of Acute Stent Thrombosis Under High-Shear Flow Conditions by a Nitric Oxide Donor, DMHD/NO

Autor: Frank Litvack, Neal L. Eigler, James S. Forrester, Masato Nakamura, Thomas C. Hutsell, Sanjay Kaul, Prediman K. Shah, Raj Makkar
Rok vydání: 1996
Předmět:
Zdroj: Circulation. 94:2228-2234
ISSN: 1524-4539
0009-7322
DOI: 10.1161/01.cir.94.9.2228
Popis: 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 P P =.3). Heparin (200 U/kg) reduced TW by 33% (14±4 versus 21±3 mg control, P 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.
Databáze: OpenAIRE