An animal model for the study of arterial thrombosis

1. Thrombus formation induced by electrical stimulation of the carotid artery was investigated in anesthetized rabbits and rats. Occlusive Grade III thrombi were produced consistently in 34 normal New Zealand rabbits and 58 untreated albino Wistar rats. Thrombus formation was monitored continuously in some of the animals with a magnetic flowmeter or a thermistor probe applied on the carotid. 2. The usefulness of the model for the screening of drugs was tested by treating the animals with warfarin, heparin, prostacyclin (PGI2), dihydroprostacyclin (DiHPGI2), prostaglandin E1 (PGE1), and prostaglandin D2 (PGD2). 3. All of the drugs except warfarin were infused continuously into the venous circulation during the entire experimental period at a rate of 0.2 ml/min. 4. Warfarin (10 mg/kg), administered by gavage 24 h before the experiment, prevented thrombus formation, as did heparin iv (greater than 34 U/kg). 5. Of the four platelet antiaggregatory prostaglandins tested, PGI2 was the most potent inhibitor of thrombus formation and DiHPGI2 the least active, as evaluated by visual inspection of stimulated arterial segments which were excised 30 min (rabbits) or 15 min (rats) after the stimulation was stopped. PGI2 was less active in rats than in rabbits (Threshold Protective Dose ratio ca. 4:1). PGE1 and PGD2 showed intermediate activity in both animal models.