The effects of recombinant desulphatohirudin on arterial thrombosis in rats.
The role of thrombin in the formation of arterial thrombi is poorly understood. With the new availability of the specific thrombin inhibitor, recombinant desulphatohirudin, in large quantities this is now under investigation. A new model of arterial thrombosis in rats is described where a thrombus is formed on a mechanically injured vessel in vivo. Both platelet and fibrin deposition is inhibited by a recombinant hirudin (CGP 39393) at doses which prolong the activated partial thromboplastin time (APTT) to no more than 3-4 times the control level. In contrast, both unfractionated heparin and Fragmin only inhibit thrombosis when the APTT is excessively prolonged (i.e. to greater than 15 times the control value). It is concluded that CGP 39393 is an effective antithrombotic in arterial thrombosis at lower levels of anticoagulation than either heparin or Fragmin.
Talbot
M D
MD
Thrombosis Research, Research Centre, Ciba-Geigy Pharmaceuticals, Horsham, UK.
Ambler
J
J
Butler
K D
KD
Lees
C M
CM
Mitchell
K A
KA
Peters
R F
RF
Tweed
M F
MF
Wallis
R B
RB
D000818:Animals; D001012:Aorta, Abdominal / Q000293:injuries; D003250:Constriction; D005337:Fibrin / Q000032:analysis; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives*; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000188:drug therapy* / Q000517:prevention & control
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D011994:Recombinant Proteins; D005337:Fibrin; D006493:Heparin; C060225:desirudin