Failure of diltiazem to suppress cholesterol-induced atherogenesis of endothelium-denudated arteries in pigs

Abstract

To investigate the effect of diltiazem on the development of atherosclerosis, 15 pigs were fed a fat-poor basal diet to which 8% (w/w) lard fat and 2% (w/w) cholesterol were added for 8 months. To enhance the formation of atherosclerotic plaques endothelium of the aorta and the left anterior descending coronary artery was removed after 1 month and 0.5% (w/w) bile acids were added to the diet after 3 months. Seven animals served as control, while 8 animals also received diltiazem (the first 2 months 10 mg/kg twice daily and during the remainder of the dietary period 5 mg/kg twice daily). The diet-induced increases in plasma level of total cholesterol were not affected by diltiazem. Triglyceride levels did not change in the control group but decreased significantly in the diltiazem-treated animals. Collagen-induced (1 μg/ml) platelet aggregation was increased by diltiazem. The sum of free and esterified cholesterol was increased in the lesions of the aortic wall in the diltiazem-treated animals (9.8 ± 1.3 μg/g wet weight vs. 6.3 ± 1.0 μmol/g wet weight in the untreated animals), but coverage of the aorta with sudanophilic lesions was similar for both groups (40 ± 4% for the treated and 34 ± 9% for the control animals). Narrowing of the previously abraded coronary arteries was similar for the diltiazem-treated (median 7.1%, ranges 2.6–29.0%) and the control group (median 10.0%, ranges 2.3–24.1%). It is concluded that the dose range of diltiazem of 5–10 mg/kg twice daily, which is close to that used in the clinical setting, had no effect on the experimentally induced atherogenesis in pigs.