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.