ANTITHROMBOTIC ACTIVITY OF DERMATAN SULFATES, HEPARINS AND THEIR COMBINATION IN AN ANIMAL-MODEL OF ARTERIAL THROMBOSIS

Dermatan sulphates have been shown to inhibit thrombus formation and t hrombus growth in different experimental models of venous thrombosis. At variance with heparins, they show a remarkably low haemorrhagic pot ential. On the other hand, very few data are available on the effect o f dermatan sulphates an arterial thrombus formation. We evaluated the effects of a low molecular weight (LMW)-dermatan sulphate, a high mole cular weight (HMW)-dermatan sulphate and sulodexide (a mixture of fast -moving heparin fraction and dermatan sulphate) in comparison with LMW - and HMW-heparin, in a model of arterial thrombosis in rats. The inse rtion of an artificial prosthesis into the abdominal aorta of the anim als induced the formation of an occluding thrombus within 2-5 days. Th e time in which 50% of the loops became occluded (OT50) was also calcu lated and used to compare the efficacy of the different drug treatment s. This was 2.84 days for control animals and 4.25 and 5.80 days for H MW- and LMW-dermatan sulphate, respectively. Neither drug changed the ''template'' bleeding time, even at higher doses. In contrast, HMW-hep arin at doses (8 mg/kg, sc, twice a day) inducing an antithrombotic ac tivity comparable to that of dermatan sulphates, dramatically prolonge d the bleeding time. LMW-heparin at the same doses was ineffective. Su lodexide (10 mg/Kg, sc, twice a day) prolonged the occlusion time to t he same extent as HMW-heparin (OT50 5.10 vs. 4.14 days), with less an effect on the bleeding time (144+/-6 s vs. >300 s, respectively). Hist ological examination confirms that the prolongation of occlusion time induced by the drugs is really related to thrombus formation inhibitio n at the site of arterial wall injury. Acetyl salicylic acid (ASA) (10 0 mg/kg/day in drinking water as lysine acetylsalicylate) did not modi fy the effect of Desmin 370 and Sulodexide on both occlusion and bleed ing time. However, while it did not increase the antithrombotic activi ty of HMW-heparin, it significantly prolonged its haemorrhagic effect. In conclusion, dermatan sulphates are effective inhibitors of arteria l thrombosis in rats. without inducing bleeding complications.