Author + information
- Received November 19, 1984
- Revision received January 28, 1985
- Accepted February 21, 1985
- Published online July 1, 1985.
- Gregory D. Tilton, MDa,
- L. Maximilian Buja, MD, FACC,
- David W. Bilheimer, MD,
- Phillip Apprill, MD,
- Juliet Ashton, PhD,
- Janice McNatt,
- Toru Kita, MD and
- James T. Willerson, MD, FACC
- ↵aAddress for reprints: Gregory D. Tilton, MD, University of Texas Health Science Center at Dallas, Ischemic Heart Center, Room L5.134, 5323 Harry Hines Boulevard, Dallas, Texas 75235.
Verapamil and other slow channel calcium antagonists have been reported to retard atherosclerosis in rabbits fed a high cholesterol diet. Because atherosclerosis in such a model may differ significantly from human atherosclerosis, experiments were conducted to prevent atherosclerosis with verapamil in the Watanabe heritable hyperlipidemic (WHHL) rabbit, which is a genetic, metabolic and pathologic model of homozygous familial hypercholesterolemia. At 2 months of age, 23 WHHL rabbits were divided into two groups since earlier studies showed no macroscopic atherosclerosis at 2 months. Group A (n = 11) was fed standard rabbit chow for 6 months. Group B (n = 12) received oral verapamil (46 mg/kg per day) absorbed in the identical chow as fed to Group A and subcutaneous verapamil (0.25 mg/kg twice daily 6 days a week). In Group B, mean serum verapamil concentrations (± SEM) averaged 16.9 ± 1.9 ng/ml at 3 hours after subcutaneous injection. Sex ratios and serum cholesterol concentrations were the same in both groups. The percent of aortic surface area with visible plaque in Group A versus B was 49 ± 7 versus 43 ± 7%, respectively, of the entire aorta, and 61 ± 5 versus 65 ± 5%, respectively, of the proximal 3 cm of aorta (p = NS). Thus, verapamil did not suppress atherosclerosis in WHHL rabbits at serum drug levels greater than those reported to be effective in other models.
This study was supported by Ischemic SCOR Grants HL-17669 and HL-15949 from the National Heart, Lang, and Blood Institute, Bethesda, Maryland, Grant ROI-31581 from the National Institutes of Health, Bethesda, Maryland and the Moss Heart Fund, Dallas, Texas.
- Received November 19, 1984.
- Revision received January 28, 1985.
- Accepted February 21, 1985.
- American College of Cardiology Foundation