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EFFECT OF SELECTIVE ENDOPEROXIDE/THROMBOXANE A 2 RECEPTOR ANTAGONISM WITH SULOTROBAN ON tPA‐INDUCED THROMBOLYSIS IN A RABBIT MODEL OF FEMORAL ARTERIAL THROMBOSIS
Author(s) -
FUJITA T.,
HASAN S.,
STORER B.L.,
SHEBUSKI R.J.
Publication year - 1989
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1989.tb00465.x
Subject(s) - femoral artery , medicine , thrombolysis , plasminogen activator , t plasminogen activator , fibrinolytic agent , pharmacology , thrombus , tissue plasminogen activator , bolus (digestion) , anesthesia , thromboxane , platelet , myocardial infarction
Summary— The thrombolytic efficacy of recombinant tissue‐type plasminogen activator (tPA) in the presence and absence of the selective endoperoxide/thromboxane A 2 (TXA 2 ) receptor antagonist, sulotroban (BM 13.177, SK&F 95587) was studied in a model of femoral artery thrombosis in the anesthetized rabbit. The thrombus was formed by injection of thrombin, CaCl 2 and whole blood into an isolated segment of the femoral artery. After 30 min of stable thrombotic occlusion of the femoral artery, tPA was infused IV for 90 min at doses of 5.0, 7.5 and 10.0 μg/kg/min. In other experiments, sulotroban was administered as a bolus dose of 1 mg/kg/IV, followed by a constant infusion of 1 mg/kg/hr concurrent with tPA infusion. Sulotroban had no effect on the incidence of tPA‐induced reperfusion at any dose studied or on residual clot weight. However, at a tPA dose of 10 μg/kg/min, IV lysis time was reduced in sulotroban treated animals from 65 min to 29 min ( P <0.05), and the magnitude of femoral artery blood flow achieved as a result of tPA‐induced reperfusion was greater in sulotroban‐treated animals. These data suggest that adjunctive therapy with a selective endoperoxide/TXA 2 antagonist improves the response to tPA when tPA is administered at a maximal or near maximally effective pharmacological dose.