EFFECT OF LOW-MOLECULAR-WEIGHT HEPARIN ON INTIMAL HYPERPLASIA

Intimal hyperplasia is a significant cause of vascular graft failure. To investigate the potential uses of low molecular weight heparins (LMWHs) as prophylactic agents against graft thrombosis in humans, the anti-proliferative effects of a regimen of subcutaneous LMWH have been studied in an experimental model. Aortic intimal hyperplasia was created in 30 New Zealand White rabbits by endothelial denudation using an embolectomy balloon catheter technique. Three groups of ten animals were randomized to act as controls or to be treated with subcutaneous LMWH once or twice daily for 4 weeks. At 4 weeks all animals were killed and the aortas were harvested for analysis. The degree of intimal hyperplasia was measured using a computerized image analysis system and was expressed as an intimal:medial area ratio and also as percentage luminal reduction. A 60 per cent reduction in the degree of intimal hyperplasia was seen following treatment with LMWH. Heparin-treated animals had considerably less luminal reduction (daily LMWH 8 per cent and twice-daily LMWH 10 per cent) compared with untreated controls (26 per cent) (P < 0.001). There was a similar difference seen in the intima:media area ratios, daily LMWH 0.38, and twice-daily LMWH 0.44, versus controls, 1.11 (P < 0.001). In an experimental model, subcutaneous LMWH therapy effectively inhibits intimal hyperplasia.