Antithrombotic effect of two low molecular weight thrombin inhibitors and a low-molecular weight heparin in a caval vein thrombosis model in the rat.
A sensitive thrombosis model with a high reproducibility was developed in the rat, utilizing stasis of the caval vein and a standardized surgical trauma as the only thrombogenic stimuli. Since no procoagulant substances were used, the results of the present study might be relevant in a clinical situation. The antithrombotic effect of two recently synthesized low-molecular-weight thrombin inhibitors have been compared to dalteparin, (Fragmin) a low-molecular-weight heparin fragment. Each compound was studied at 8 different doses with 10 rats in each group. On a gravimetric basis, the thrombin inhibitor melagatran was twice as potent as dalteparin (ED50 16 and 33 microg/kg per h, respectively). The second thrombin inhibitor, inogatran, had an intermediate effect, with an ED50 of 24 microg/kg per h. No differences in antithrombotic effect were, however, found when the compounds were compared at anticoagulant equivalent doses (same APTT prolongation). A 50% reduction in the mean thrombus weight was obtained when APTT was prolonged to 1.2 to 1.3 times the pretreatment value.
Eriksson
B I
BI
Department of Orthopaedics, Sahlgrenska University Hospital, University of Göteborg, Sweden.
Carlsson
S
S
Halvarsson
M
M
Risberg
B
B
Mattsson
C
C
D000818:Animals; D001384:Azetidines; D001596:Benzylamines; D017985:Dalteparin / Q000627:therapeutic use; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005998:Glycine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D010880:Piperidines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013924:Thrombophlebitis / Q000188:drug therapy*; D014682:Vena Cava, Inferior
D001384:Azetidines; D001596:Benzylamines; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D010880:Piperidines; C109573:melagatran; C099871:inogatran; D013917:Thrombin; D017985:Dalteparin; D005998:Glycine