Comparative effects of heparin and PK 10169, a low molecular weight fraction, in a canine model of arterial thrombosis.
The comparative properties of heparin and PK 10169, a low molecular weight fraction, were studied using an antithrombotic test in anaesthetized dogs. The antithrombotic properties of the two compounds were evaluated by measuring inhibition of thrombus formation following transluminar stimulation of coronary artery with anodal current and by measuring anticoagulant properties, anti Xa and anti IIa activities. The results show that PK 10169 displayed significant antithrombotic activities above 0.625 mg/kg and was equipotent at 2.5 mg/kg s.c. with heparin 10 mg/kg s.c. No correlation could be observed between antithrombotic/anti Xa ratio of both compounds. Moreover it was shown that, unlike heparin, PK 10169 s.c. was devoid of obvious anticoagulant properties and induced a negligible anti IIa activity contrasting with a high anti Xa level. A similar dissociation between anti Xa and anti IIa activities was observed following i.v. administration of 2.5 mg/kg of PK 10169 but not with heparin. This low molecular weight heparin fraction might thus be regarded as a potential arterial antithrombotic agent devoid of appreciable anticoagulant effect.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use*; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013997:Time Factors
D011516:Prothrombin; D005170:Factor X; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa