PROBUCOL DECREASES NEOINTIMAL FORMATION IN A SWINE MODEL OF CORONARY-ARTERY BALLOON INJURY - A POSSIBLE ROLE FOR ANTIOXIDANTS IN RESTENOSIS

Background. Restenosis after percutaneous transluminal coronary angiop lasty is the major limitation of the long-term success of this procedu re. The process of restenosis is similar to an accelerated form of ath erosclerosis. Thus, therapeutic interventions that limit the progressi on and initiation of atherosclerosis may be beneficial in the treatmen t of restenosis. One such intervention is the antioxidant drug probuco l, which has demonstrated benefit in animal models of atherosclerosis. Methods and Results. Twenty-six female domestic swine were divided in to three study groups (control, n=9; low-dose probucol, n=9; high-dose probucol, n=8) before oversized balloon injury of the left anterior d escending and left circumflex coronary arteries. Probucol (1 g/d, low- dose group; 2 g/d, high-dose group) was administered 2 days before bal loon injury and was continued until the swine were killed 2 weeks afte r balloon injury. Morphometric analysis of the injured arteries includ ed the intimal area (square millimeters), maximal intimal thickness (m illimeters), and residual lumen (ratio of luminal to intimal plus lumi nal area). Treatment with high-dose probucol significantly reduced neo intimal formation compared with control animals (decreases of 36% in i ntimal area, P=.007; 20% in maximal intimal thickness, P=NS; and an in crease of 15% in residual lumen, P=.02). Conclusions. The major findin g of this study is that the antioxidant drug probucol reduces neointim al formation after oversized balloon injury in a swine model of resten osis. This suggests that active oxygen species may play a role in rest enosis.