Effect of lovastatin on intimal hyperplasia after balloon angioplasty: A study in an atherosclerotic hypercholesterolemic rabbit

Abstract

Restenosis, the major limitation of balloon angioplasty, is the result of intimai hyperplasia after the procedure. Lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitor, may influence intimai hyperplasia by lowering serum cholesterol and by blocking deoxyribonucleic acid (DNA) synthesis. To determine whether lovastatin reduces intimai hyperplasia, a prospective, randomized blinded study was performed in 60 atherosclerotic New Zealand White male rabbits. Atherosclerosis was produced by air desiccation injury followed by a 28 day diet of 2% cholesterol and 6% peanut oil that was terminated before balloon angioplasty was performed. Angioplasty could not be performed in 14 rabbits with bilateral femoral artery occlusion, and in one rabbit the procedure was a technical failure.Forty-five rabbits underwent balloon angioplasty performed with use of a 2.5-mm balloon inflated to 10 atm for three l min dilations at 1 min intervals. Seven rabbits died during the procedure. Thirty-eight rabbits were randomized to either a lovastatin group (6 mg/kg body weight per day) or a control group. Angioplasty was performed on all patent vessels (n = 54); the procedure was bilateral in 16 rabbits and unilateral in 22. Fifteen lovastatin-treated and 15 control rabbits survived 39 days after angioplasty and were then killed. Angiograms, obtained before and 10 nin and 39 days after balloon angioplasty, were read with use of electronic calipers by two observers who had no knowledge of treatment data. After the rabbits were killed, vessels were pressure perfused using a standardized protocol to maintain in vivo dimensions for minded quantitative histologic analysis.After balloon angioplasty, total cholesterol decreased 36 ± 13% (mean ± SEM) in the lovastatin group (p < 0.05) and 26 ± 15% in the control group (p < 0.05, one-sided ttest). The percent decrease in angiographic luminal diameter from 10 min to 34 days after angioplasty was less in the lovastatin group (n = 22) than in the control group (n = 23) (reader 1:13 ± 11% versus 47 ± 8%, p < 0.05; reader 2:17 ± 8% versus 47 ± 8%, p < 0.01). Intimal thickness was 0.16 ± 0.02 mm in the lovastatin group and 0.30 ± 0.04 mm in the control group (p < 0.01). Thus, lovastatin reduced intimal hyperplasia after balloon angioplasty of the femoral artery in the hypercholesterolemic atherosclerotic rabbit. Its effect in patients undergoing coronary angioplasty should be evaluated.