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 sulfate, on the extent of lysis of radiolabelled pulmonary emboli in rats was evaluated. 125I-fibrin labelled blood clots were embolized into the 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 increase 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 epsilon-aminocaproic acid (1 g/kg). At comparable antithrombotic dosages, heparin (2 mg/kg) also produced a significant enhancement of thrombolysis while hirudin (2 mg/kg) was totally ineffective. Heparin, however, produced a much more pronounced anticoagulant effect than D370. No changes in the plasma levels of plasminogen activator and plasminogen activator inhibitor activities were observed after treatment with D370. Moreover, the dermatan sulfate failed to enhance the blood fibrinolytic activity measured by a solid phase 125I-fibrin assay. These results extend previous data indicating that D370 may be efficient also in the therapy of thrombosis and provide direct evidence that this effect occurs, at least in part, via degradation of thrombus associated fibrin.
Colucci
M
M
Department of Biomedical Sciences and Human Oncology, University of Bari, Italy.
Sardella
L
L
Barbanti
M
M
Calanni
F
F
Semeraro
N
N
D000818:Animals; D003893:Desmin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use; D024764:Hirudin Therapy; D008297:Male; D010314:Partial Thromboplastin Time; D011655:Pulmonary Embolism / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015912:Thrombolytic Therapy
D003893:Desmin; D005343:Fibrinolytic Agents; D006493:Heparin