In vivo method for quantitation of anti-platelet potency of drugs

Abstract

Summary Aortic strips from atherosclerotic rabbits or Achilles tendons from healthy rabbits were superfused with blood (3 ml/min) from anaesthetized and heparinized cats, while blood was returned to the venous system of animals. The superfused tissues gained in weight because of deposition of platelet thrombi on their surface. This gain in weight was continuously monitored and quantified. Forty minutes after intravenous administration of indomethacin (14 mg/kg), aspirin (7 mg/kg) or nictindole (2 mg/kg) the formation of platelet deposits was reduced by half. Three hours after i.v. administration of each drug at a dose of 20 mg/kg the remaining anti-platelet activities were 92% for aspirin, 59% for indomethacin and 18% for nictindole as compared to their antithrombotic action, which was recorded 40 min after their administration. Thrombogenesis was also prevented by a direct infusion of nictindole (50 ng/ml) or indomethacin (2000 ng/ml) into a stream of superfusing blood. Thereby our method enables us to quantify in vivo anti-aggregating potency of drugs, to estimate the duration of this action, and to compare their in vitro and in vivo aggregation-inhibitory activities.