Failure of diltiazem to suppress cholesterol-induced atherogenesis of endothelium-denudated arteries in pigs.
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 microgram/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 micrograms/g wet weight vs. 6.3 +/- 1.0 mumol/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.
Sassen
L M
LM
Laboratory for Experimental Cardiology, Erasmus University Rotterdam, The Netherlands.
Lamers
J M
JM
Hartog
J M
JM
Dekkers
D H
DH
Verdouw
P D
PD
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003094:Collagen / Q000494:pharmacology; D003331:Coronary Vessels / Q000473:pathology; D004110:Diltiazem / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D013552:Swine
D002791:Cholesterol, Dietary; D008055:Lipids; D003094:Collagen; D004110:Diltiazem