Inhibition of intimal hyperplasia after arterial injury by heparins and heparinoid

Abstract

The efficacies of standard heparin (SH), low molecular weight heparin (LMWH), and a mixture of sulfated glycosaminoglycans (Org 10172) were investigated with respect to their inhibitory effects on intimal thickening after endothelial injury in the common carotid artery of the rat. The injury was induced by air infusion into an isolated segment of the artery; the pharmacologic agents were administered by continuous intravenous infusion. After 2 weeks the animals were killed and the arteries examined. The control animals developed a marked intimal thickening. A dose-dependent decreaes in the intima to media area (I-M) ratio was seen after SH, with approximately 50% and 90% inhibition of intimal thickening at doses of 5 and 50 USP U/kg/hr, respectively. At these effective doses, the effect of SH was associated with reendothelialization of the injured area. The effects of LMWH and Org 10172 were similar to that of SH at doses of 50 anti-Xa U/kg/hr, but these agents had only about 40% inhibition at doses of 15 anti-Xa U/kg/hr. The activated partial thromboplastin times were slightly prolonged in the animals treated with 50 USP/anti-Xa U/kg/hr of SH, LMWH, and Org 10172, whereas significant anti-Xa levels were observed at doses higher than 15 USP/anti-Xa U/kg/hr. It is concluded that SH, LMWH, and Org 10172 have significant inhibitory effects of intimal thickening after injury even at nonanticoagulant levels, with SH being the most potent.