Biological and thrombolytic properties of fibrolase--a new fibrinolytic protease from snake venom.
Fibrolase, a direct-acting fibrinolytic enzyme has been shown to cleave primarily the A alpha and B beta chains of human fibrin. We have previously reported that fibrolase also exhibits fibrinogenolytic activity and acts mainly as an alpha-chain fibrinogenase. In contrast to the action of streptokinase (plasminogen activator), fibrolase does not activate plasminogen. In vitro thrombolytic efficacy of fibrolase was determined by monitoring the release of radiolabel from iodinated fibrin and human blood clots. Fibrolase effectively digested the clots in a dose-dependent manner. The in vivo efficacy of fibrolase was evaluated in an animal model of arterial thrombosis. Fibrolase was found to be efficacious at dissolving femoral arterial clots following a single intravenous bolus administration. Time to reperfusion was dose dependent and similar to that observed with streptokinase. No adverse effects on blood pressure and heart rate were observed.
Ahmed
N K
NK
Marion Merrel Dow Inc., Kansas City, Mo.
Gaddis
R R
RR
Tennant
K D
KD
Lacz
J P
JP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003435:Crotalid Venoms / Q000378:metabolism; D005263:Femoral Artery / Q000187:drug effects; D005343:Fibrinolytic Agents; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes; D008666:Metalloendopeptidases / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013300:Streptokinase / Q000378:metabolism
C031442:Agkistrodon venoms; D003435:Crotalid Venoms; D005343:Fibrinolytic Agents; D007457:Iodine Radioisotopes; D013300:Streptokinase; D008666:Metalloendopeptidases; C058789:fibrolase