Desmin 370 (D370), a low molecular weight
dermatan sulfate, has been shown to induce a marked reduction of the weight of preformed venous thrombi in rats and rabbits by mechanisms that appeared largely independent 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
thrombus growth and thus sensitive only to agents promoting
thrombus lysis.
Thrombus formation in anesthetized rats was induced by vena cava
ligature. Injection of
ancrod (5 U/kg) 5 h after induction of venous stasis caused a more than 95% reduction in plasma
fibrinogen and prevented
thrombus accretion as indicated by the lack of
thrombus weight increase 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 125I-fibrin(ogen) binding 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 interval visible thrombi were present in all control rats. Administration of D370 (10 mg/kg) to
thrombus bearing rats, 1 h after induction of
afibrinogenemia, resulted in a significant reduction in
thrombus weight (43% after 2 h, p < 0.01) which was only slightly lower than that recorded in normofibrinogenemic rats (54%). Enhancement of plasma fibrinolytic activity by
ancrod had no influence on
thrombus lysis and was not all affected by administration of D370.(ABSTRACT TRUNCATED AT 250 WORDS)