DESMIN-370, A LOW-MOLECULAR-WEIGHT DERMATAN SULFATE, REDUCES THE WEIGHT OF PREFORMED THROMBI IN RATS MADE AFIBRINOGENEMIC BY ANCROD

Desmin 370 (D370), a low molecular weight dermatan sulfate, has been s hown to induce a marked reduction of the weight of preformed venous th rombi in rats and rabbits by mechanisms that appeared large ly indepen dent of inhibition of thrombus accretion. In order to provide further support for such a mechanism, we exploited the defibrinating capacity of ancrod to obtain a thrombosis model characterized by the lack of th rombus growth and thus sensitive only to agents promoting thrombus lys is. Thrombus formation in anesthetized rats was induced by vena cava l igature. Injection of ancrod (5 U/kg) 5 h after induction of venous st asis caused a more than 95% reduction in plasma fibrinogen and prevent ed thrombus accretion as indicated by the lack of thrombus weight incr ease during the 3 h experimental period (12.2 +/- 0.6 vs 14.5 +/- 1 as compared to 12.6 +/- 0.6 vs 19.6 +/- 0.8, p < 0.01, in control rats) and by the almost complete (>90%) inhibition of I-125-fibrin(ogen) bin ding to thrombi. Moreover, when ancrod was given 1 h before vena cava ligature, no thrombi were formed within 2 h whereas at the same time i nterval visible thrombi were present in all control rats. Administrati on of D370 (10 mg/kg) to thrombus bearing rats, 1 h after induction of afibrinogenemia, resulted in a significant reduction in thrombus weig ht (43% after 2 h, p < 0.01) which was only slightly lower than that r ecorded in normofibrinogenemic rats (54%). Enhancement of plasma fibri nolytic activity by ancrod had no influence on thrombus lysis and was not at all affected by administration of D370. These data provide addi tional and more direct evidence that D370 may promote thrombus lysis i ndependently of inhibition of thrombus accretion.