Sensitivity of experimental venous and arterial thrombosis and bleeding to ancrod-induced defibrinogenation.
The effect of ancrod-induced defibrinogenation on thrombosis and bleeding time was determined in anesthetized rats. Functional plasma fibrinogen levels were reduced 42, 71, 94 and 93% by ancrod doses of 5, 10, 20 and 30 U/kg, respectively, while a 2.5 U/kg dose was without significant effect. Ancrod inhibited vena cava thrombosis induced by partial stasis of blood flow combined with mild vascular injury. Thrombus weight was decreased 85 and 93% by the 10 and 20 U/kg doses, but was unaffected at lower doses. In contrast, ancrod doses of up to 30 U/kg did not significantly decrease carotid artery thrombi formed in response to oxidative transmural vessel injury. Ancrod caused a dose-dependent increase in bleeding time measured by puncturing small mesenteric arteries with a hypodermic needle. The bleeding time increase was approximately 38% in response to the 2.5 and 5 U/kg doses, and 182% in response to the 10 U/kg dose. These studies demonstrate that ancrod-induced reductions in plasma fibrinogen more effectively inhibit venous compared to arterial thrombosis, although these activities require doses that also increase bleeding time in small arteries.
Schumacher
W A
WA
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Heran
C L
CL
Steinbacher
T E
TE
D000721:Ancrod / Q000008:administration & dosage*; D000818:Animals; D001783:Blood Flow Velocity; D002339:Carotid Arteries; D005340:Fibrinogen / Q000187:drug effects* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006470:Hemorrhage / Q000097:blood* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D014682:Vena Cava, Inferior
D005343:Fibrinolytic Agents; D005340:Fibrinogen; D000721:Ancrod