EFFECTS OF A SINGLE HEPARIN BOLUS ON NEOINTIMAL GROWTH AFTER ARTERIALINJURY IN INTACT RABBITS

Heparinization is a routine procedure during angioplasty; however, its consequences on the late vascular response to a severe injury are unc lear. The authors' objective was to explore the effect of a single hep arin bolus at the time of a severe vascular injury on late intimal pro liferation and neointimal thickening. The iliac artery of 57 normolipe mic rabbits was overdistended with a balloon catheter. Heparin (250 IU /kg IV) was given to 29 rabbits ten minutes before angioplasty, wherea s 28 rabbits served as untreated controls. Neointimal thickening was p rominent at fourteen days after injury and reached near-maximal values at day 28. The intimal/medial area ratio was reduced by an average 28 .3% with heparin (at day 28: 2.19 +/- 0.51 vs 1.57 +/- 0.59, control v s heparin, P = 0.02). Neointimal cells stained positively for HHF-35 a ntibody, directed against smooth muscle cell antigens. Neointimal prol iferation, quantified through the number of cell nuclei peroxidase-sta ined for PCNA/cyclin antigen, was significantly decreased by 43% and 4 9% with heparin, respectively, at days 7 and 14 after injury. These da ta suggest that early exposure even to low doses of heparin accounts f or much of its inhibitory effect in vascular response to injury; such an effect might prove important in;interpreting results of human trial s of interventions against restenosis.