Abstract
The antithrombotic action of antiarrhythmic peptide (AAP) was studied by using various in vivo thrombosis models. AAP (1, 10 or 100mg/kg, i.v., 10 mg/kg, i.p. or 100mg/kg, p.o.) significantly inhibited white thrombus formation on a silken thread in the extracorporeal shunt models in rats, its ED50 being about 30mg/kg, i.v. AAP (10mg/kg, i.v.) was effective in protecting rats against the decrease in platelet count, incidence of electrocardiographic alterations (T wave inversion and ST segment depression) typical of myocardial ischemia, and development of ectopic beats in the coronary thromboembolism induced by intravenous infusion of adenosine 5'-diphosphate. The peptide (10mg/kg, i.p.) was also effective in preventing thrombus formation in the lung and the decrease of platelet count induced by lactic acidosis in rats, and it (10mg/kg, i.v.) clearly inhibited thromboembolic death induced by rapid intravenous injection of collagen in mice. Daily treatments with the peptide (10mg/kg/d, i.p.) resulted in significant delay of the progression of gangrene and mummification in laurate-induced peripheral arterial occlusive disease in rats. AAP did not affect venous thrombus formation, blood flow through the carotid artery, plasma recalcification time or fibrinolytic activity in rats. It is likely that the potent antithrombotic action of AAP is mainly due to its anti-platelet-aggregating action in vivo. Ticlopidine (100mg/kg, p.o.) also showed a comparatively wide antithrombotic spectrum, like AAP, in the present thrombosis models, but ticlopidine lacked the action against myocardial ischemia, like aspirin (50mg/kg, s.c.).
