Effects of napsagatran (Ro 46-6240), a new synthetic thrombin inhibitor and of heparin in a canine model of coronary artery thrombosis: comparison with an ex vivo annular perfusion chamber model
Napsagatran, a new synthetic direct thrombin inhibitor, was compared with heparin in a canine model of coronary thrombosis and concomitantly in an ex vivo perfusion chamber model. Occlusive thrombosis of the left circumflex coronary artery was induced by electrical injury. In parallel, arterial sube...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 277; no. 1; pp. 71 - 78 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.04.1996
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Subjects | |
Online Access | Get full text |
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Summary: | Napsagatran, a new synthetic direct thrombin inhibitor, was compared with heparin in a canine model of coronary thrombosis
and concomitantly in an ex vivo perfusion chamber model. Occlusive thrombosis of the left circumflex coronary artery was induced
by electrical injury. In parallel, arterial subendothelium was exposed to native blood using an annular perfusion chamber
for 5, 10 and 20 min at a wall shear rate of 650/s. Dogs received saline, heparin (40 and 70 U/kg/h) or napsagatran (3 and
10 microgram/kg/min). Heparin (40 U/kg/h) and napsagatran (3 microgram/kg/min) delayed or prevented in vivo thrombotic occlusion,
but only napsagatran (10 microgram/kg/min) significantly decreased the intracoronary thrombus when compared with saline. High-dose
heparin (70 U/kg/h) or napsagatran (10 microgram/kg/min) decreased the platelet-rich thrombus after a 20-min chamber perfusion.
Neither heparin nor napsagatran decreased the thrombus volume after a 5-min perfusion. Heparin (70 U/kg/h) and napsagatran
(10 microgram/kg/min) prolonged the activated partial thromboplastin time differently (>x6 and x1.4, respectively, P<0.01),
whereas the activated clotting time was prolonged equally (x2.5). Thus napsagatran in this model shows arterial antithrombotic
effects similar to those of heparin. The chamber experiments suggest that neither compound affects the initiation of platelet
thrombus formation. In arterial thrombosis, the activated clotting time has a higher predictive value than the activated partial
thromboplastin time when a direct thrombin inhibitor is compared with heparin. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3565 1521-0103 |