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 intimal hyperplasia after the procedure. Lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitor, may influence intimal hyperplasia by lowering serum cholesterol and by blocking deoxyribonucleic acid (DNA) synthesis. To determine whether lovastatin reduces intimal 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 1 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 min 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 blinded quantitative histologic analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

HMG CoA reductase inhibitors. In vivo effects on carotid intimal thickening in normocholesterolemic rabbits.

“…Pharmacological approaches, including heparin, calcium antagonists, and angiotensin converting enzyme inhibitors, have been tried with variable success. 39 Lovastatin prevents restenosis in hypercholesterolemic rabbits undergoing femoral balloon angioplasty 19 and reduces restenosis rates after percutaneous transluminal coronary angioplasty in humans. 20 However, it is difficult to extrapolate from these studies any direct effect of vastatins on arterial myocyte proliferation.…”

“…Compactin and simvastatin inhibit smooth muscle cell growth in vitro. 16 - 18 Aggressive lipid-lowering treatment with lovastatin prevented restenosis after balloon angioplasty in hypercholesterolemic rabbits 19 and humans. 20 However, no correlations between serum cholesterol and restenosis were found in percutaneous transluminal coronary angioplasty patients.…”

Intravascular Ultrasound Guidance Improves Angiographic and Clinical Outcome of Stent Implantation for Long Coronary Artery Stenoses

“…23 We also found that statin use was independently associated with better angiographic and clinical outcome. Although several researchers have found that smooth muscle cell proliferation is inhibited by statin use, 24,25 only a few studies directly investigated the possible effects of this therapy on restenosis after stenting. The present data corroborate the reduction of in-stent restenosis and improved clinical outcome reported by Walter et al 26 in a nonrandomized study of the effects of statins after stenting.…”

Inhibition of human vascular smooth muscle cell proliferation by lovastatin: the role of isoprenoid intermediates of cholesterol synthesis

“…Lovastatin is used in the treatment of hypercholesterolaemia and has been shown to prevent restenosis in a hypercholesterolaemic rabbit model of restenosis [9] and in one human coronary restenosis trial [lo]. Lovastatin competitively inhibits 3-hydroxy-3 methylglutaryl-coenzyme A (HMG CoA) reductase [I I], the rate-limiting enzyme in cholesterol biosynthesis.…”