A NEW SINGLE-INJURY MODEL OF BALLOON ANGIOPLASTY IN CHOLESTEROL-FED RABBITS - BENEFICIAL EFFECT OF HIRUDIN AND COMPARISON WITH DOUBLE-INJURY MODEL

Air desiccation endothelial injury followed by cholesterol feeding is known to induce focal femoral atherosclerosis in rabbits. We previousl y demonstrated the effectiveness of hirudin in limiting restenosis aft er balloon angioplasty (BA) in this double instrumentation injury (DI) model. In the present study, we sought to determine whether BA withou t prior air desiccation endothelial injury (single instrumentation inj ury (SI)) would lead to similar femoral lesions, and whether the respo nse to this injury might also be limited by hirudin. Accordingly, 38 f emoral arteries of cholesterol-fed rabbits underwent BA with (n = 18, DI group) or without (n = 20, SI group) prior air desiccation endothel ial injury. Animals were killed 24 hours or 28 days after BA. Twenty-f our hours after BA, the SI group (n = 10) had a significantly smaller percentage of cross-sectional area narrowing by plaque than the DI gro up (n = 8) (0% Versus 42% +/- 9%, p = 0.008). However, 28 days after B A, the percentages of cross-sectional area narrowing by plaque in the SI (n = 10) and DI (n = 10) groups were similar (59% +/- 6% versus 68% +/- 1%, p = NS). The percentages of intima (16% +/- 3% versus 16% +/- 3%, p = NS) and media occupied by foam cells were also similar in the two groups. To test whether hirudin administration would limit arteri al narrowing after injury in the SI model, we randomly assigned choles terol-fed rabbits that had not undergone air desiccation injury to eit her bolus hirudin followed by repeat dosing 24 hours after BA or bolus heparin (150 U/kg) at the time of BA. The hirudin-treated group showe d significantly less angiographic and histologic restenosis 28 days af ter BA, despite no difference in early (0 to 72 hours) cumulative cell ular proliferation between the two groups. Thus, in the cholesterol-fe d rabbit, plaque formation and foam cell accumulation are similar afte r BA of a non-air-desiccated (SI) or focally atherosclerotic (DI) arte ry. Thrombin inhibition with hirudin limits arterial narrowing after S I, further emphasizing the role of thrombin in neointimal growth after injury.