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Warfarin sodium (Coumadin) has been used as an effective anticoagulating agent in human medicine for many years, although careful monitoring of its effects are necessary to avoid excessive anticoagulation. Previous experience with this drug for chronic anticoagulation therapy in miniature swine has been limited. The effect of warfarin sodium was studied by measuring prothrombin time in twelve 8-month-old Hanford miniature swine. The pigs had been fed a high-cholesterol diet and had undergone a prior coronary artery abrasion procedure for development of an atherosclerotic coronary disease model. Atherosclerosis was induced by feeding a high-cholesterol diet. Baseline prothrombin time ranged from 12.8 to 15.0 s (13.7 s mean). Prothrombin time was determined daily for the first 5 days of treatment and at least twice weekly thereafter until the animals were sacrificed. Animals received warfarin for 37-41 days. Prothrombin time could be increased 33-50% by once daily oral administration of warfarin 0.04-0.08 mg/kg. Oral administration of more than 0.08 mg/kg as a maintenance dose resulted in the death of two pigs. Most animals responded well to 0.08 mg/kg for the first 3 days of treatment followed by a maintenance dose of 0.06 mg/kg. Dosage was adjusted periodically when prothrombin times exceeded 50% above baseline. It is our experience that monitoring prothrombin time at least twice weekly and adjusting the maintenance dose can eliminate death losses due to warfarin intoxication.

The susceptibilities of male and female mini-pigs of the Göttingen strain to experimental hyperlipoproteinemia and atherosclerosis were studied and compared. Hyperlipoproteinemia was induced in groups of pigs of each sex by adding 11.2% egg yolk and 0.5% cholesterol to the diet. The initial increase in the plasma cholesterol concentration was significantly greater in the female animals than in the male ones. In both sexes most of the increase in plasma cholesterol was referable to the low-density lipoprotein fraction. As the experiment proceeded, the difference in the plasma cholesterol level between the sexes became less pronounced. After 18 months on the lipid-rich diet the animals were slaughtered and examined for atherosclerotic lesions. Specimens from the coronary arteries and the thoracic and abdominal aorta were taken for lipid analyses. From colour photographs of the intimal surface of the aorta, the percentage area of visible atherosclerosis in the abdominal part was calculated. Atherosclerotic lesions were present in the coronary arteries and in the abdominal aorta in both sexes. In the abdominal aorta, the results of the lipid analyses, and the calculated percentage area of atherosclerosis, indicated that the degree of atherosclerosis was similar in male and female pigs. In the coronary arteries, the atherosclerosis was more pronounced in the female pigs, as judged from the accumulation of cholesterol.