POTENTIATION OF THROMBOLYTIC THERAPY BY ENZYME COMBINATIONS AND WITH ASPIRIN OR PENTOXIFYLLINE

Radioactively labeled human fibrin clots were placed into veins of Mac aca arctoides monkeys. Thrombolysis was recorded by the disappearance of radioactivity and by angiography. Streptokinase (SK) and urokinase (UK) induced thrombolysis was potentiated by low dose aspirin (ASA) an d pentoxifylline (PE). Studies on the mechanisms of action revealed th at PE inhibits platelet aggregation, releases tissue plasminogen activ ator (t-PA) from the endothelium, increases red cell deformability and inhibits white cell adhesion. Thrombolysis by pro-urokinase (pro-UK) was potentiated by low dose SK probably because of streptokinaseplasmi n activation of pro-UK to UK. Platelet aggregation inhibitory effects, disaggregation of platelet aggregate inducing effects, and the t-PA r eleasing activity of PE was demonstrated in patients with obstructive cardiovascular disease. Pharmacodynamic studies suggested that PE meta bolites one and five are most effective from this point of view. These metabolites are currently studied in combination with thrombolytic en zymes.