THROMBOLYSIS ENHANCING ACTIVITY OF A LOW-MOLECULAR-WEIGHT DERMATAN SULFATE (DESMIN-370) IN EXPERIMENTAL PULMONARY-EMBOLISM IN RATS

The effect of Desmin 370 (D370), a low molecular weight dermatan sulfa te, on the extent of lysis of radiolabelled pulmonary emboli in rats w as evaluated. I-125-fibrin labelled blood clots were embolized into th e lungs via a jugular vein, and the degree of lysis was calculated, at predetermined intervals, by the residual radioactivity in the lungs. A single i.v. injection of D370 (50 mg/kg) caused a significant increa se in the rate of lysis, which was visible at 30 min and persisted for the whole experimental period (2 h). This effect was prevented by E-a minocaproic acid (1 g/kg). At comparable antithrombotic dosages, hepar in (2 mg/kg) also produced a significant enhancement of thrombolysis w hile hirudin (2 mg/kg) was totally ineffective. Heparin, however, prod uced a much more pronounced anticoagulant effect than D370. No changes in the plasma levels of plasminogen activator and plasminogen activat or inhibitor activities were observed after treatment with D370. Moreo ver, the dermatan sulfate failed to enhance the blood fibrinolytic act ivity measured by a solid phase I-125-fibrin assay. These results exte nd previous data indicating that D370 may be efficient also in the the rapy of thrombosis and provide direct evidence that this effect occurs , at least in part, via degradation of thrombus associated fibrin. (C) 1997 Elsevier Science Ltd.