Summary
These studies describe experimental conditions where aspirin is less effective than
other antiplatelet and anticoagulant drugs in inhibiting acute arterial thrombosis.
External electrolytic injury of the rat carotid artery was used to induce occlusive
thrombi in 97% of vehicle-treated rats. Thrombi were revealed by light and electron
microscopy to be comprised primarily of platelets enmeshed in a fibrin network. The
thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl chloromethy ketone (PPACK; 6
mg/kg, i. v.) decreased thrombus weight by 90%. Aspirin alone (1, 10 and 30 mg/kg,
i. v.), dipyridamole alone (5 mg/kg i. v.) and aspirin (1 and 10 mg/kg, i. v.) in
combination with dipyridamole (5 mg/kg, i. v.) did not inhibit thrombosis. The platelet-activating
factor (PAF) antagonist, WEB 2086, (1 mg/kg i. v.) was also ineffective. Other drugs
had intermediate activity. Thrombi were decreased 56% by the thromboxane receptor
antagonist, BMS 180,291, either alone (5.8 mg/kg i.v.) or in combination with aspirin
(10 mg/kg, i.v.). Heparin (900 U/kg, i.v.), warfarin (0.25 mg/kg, p.o. once daily
for 3 days) and ticlopidine (200 mg/ kg, p.o. once daily for 3 days) reduced thrombus
weight by 63, 73 and 43% respectively. Reductions in thrombus weight were always associated
with improvements in either average blood flow or vessel patency.
