Potentiation of thrombolytic therapy by enzyme combinations and with aspirin or pentoxifylline.
Radioactively labeled human fibrin clots were placed into veins of Macaca 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) and pentoxifylline (PE). Studies on the mechanisms of action revealed that PE inhibits platelet aggregation, releases tissue plasminogen activator (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 streptokinase-plasmin activation of pro-UK to UK. Platelet aggregation inhibitory effects, disaggregation of platelet aggregate inducing effects, and the t-PA releasing activity of PE was demonstrated in patients with obstructive cardiovascular disease. Pharmacodynamic studies suggested that PE metabolites one and five are most effective from this point of view. These metabolites are currently studied in combination with thrombolytic enzymes.
Ambrus
J L
JL
Buffalo General Hospital, State University of New York at Buffalo 14203.
Ambrus
C M
CM
Stadler
S
S
Toumbis
C
C
Markus
G
G
D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008251:Macaca; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use*; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000188:drug therapy*; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000627:therapeutic use*
D011994:Recombinant Proteins; D013300:Streptokinase; D014568:Urokinase-Type Plasminogen Activator; D001241:Aspirin; D010431:Pentoxifylline; C067551:saruplase