Mouse antithrombotic assay: a simple method for the evaluation of antithrombotic agents in vivo. Potentiation of antithrombotic activity by ethyl alcohol

Abstract

We present a simple method for screening antithrombotic agents. When male Swiss-Webster mice (25-34 g; N = 143) were given an i.v. injection of 0.1 ml of a mixture of collagen (dose, 15 micrograms/mouse) and epinephrine (dose, 1.8 micrograms/mouse), 94% died within 5 min or remained paralyzed for more than 15 min. Examples of the use of the system for the study of antithrombotic agents are given. Solutions of agents were administered to the animals i.p. about 1 hr before the thrombotic challenge. Aspirin (20 mg/kg), OKY-1581 (30 mg/kg) and ethanol (2 gm/kg), administered as single agents in aqueous medium, protected (P less than .01, chi 2 test) 40, 50 and 35% of the animals, respectively. Heparin (150 U/kg) was ineffective. Combinations of ethanol with indomethacin or indobufen provided complete protection, whereas ethanol plus aspirin protected 84% of the animals and ethanol plus OKY-1581 protected 70% of the animals. Dipyridamole alone (3 mg/kg), dipyridamole (1.65 mg/kg) plus ethanol or dipyridamole (1.65 mg/kg) plus aspirin were ineffective. The method appears well suited for screening potential antithrombotic agents which act primarily against platelet thromboembolism.