In:
Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 2 ( 2003-02), p. 468-474
Abstract:
Background and Purpose— Factor Xa (FXa) is a key coagulation protease and target for novel antithrombotic agents for prevention and treatment of diverse thromboembolic disorders. In the present study we describe the effect of a novel, potent, and selective FXa inhibitor, DPC602, on brain damage and neurobehavioral consequence in a rat thromboembolic model of stroke. Methods— Thromboembolic stroke was induced in rats by placement of an autologous clot into the middle cerebral artery. Results— Laser-Doppler monitoring of cerebral blood flow demonstrated that DPC602 (8 mg/kg, single IV/IP bolus pretreatment) markedly improved cerebral blood flow after thromboembolic stroke by 25% to 160% (n=6; P 〈 0.001) at 1 to 6 hours. DPC602 demonstrated concentration- and time-dependent reductions in infarct size, with maximal effect (89% reduction; n=14; P 〈 0.001) at the highest dose over controls. Neurological function was also significantly improved in DPC602-treated rats at days 1, 3, and 7 (n=13; P 〈 0.01). DPC602 treatment did not cause cerebral hemorrhage, assessed by free hemoglobin in the ischemic brain tissues. Conclusions— These data suggest that anticoagulation with a selective FXa inhibitor might ameliorate the extent of ischemic brain damage and neurological deficits after a thromboembolic event. Enhanced clot dissolution and early reperfusion may account for the cerebrovascular-protective effect of the drug.
Type of Medium:
Online Resource
ISSN:
0039-2499
,
1524-4628
DOI:
10.1161/01.STR.0000049765.81774.A3
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2003
detail.hit.zdb_id:
1467823-8
