The thrombolytic efficacy of recombinant
tissue-type plasminogen activator (tPA) in the presence and absence of a
thromboxane synthase inhibitor was studied in a model of femoral artery
thrombosis in the anesthetized rabbit. The
thrombus was formed by injection of
thrombin and whole blood into an isolated segment of the femoral artery. After 30 min of stable thrombotic occlusion of the femoral artery,
sodium heparin (300 U/kg, i.v.) was administered and tPA was infused locally to the site of the
thrombus for 30 min at 0.01, 0.10 or 1.0 microgram/kg/min. In other experiments,
CGS 13080, a selective
thromboxane synthase inhibitor, was administered at a dose of 2 mg/kg i.v., 5 min before tPA was infused and at the end of the 30 min tPA infusion. Pretreatment with
CGS 13080 resulted in a shorter time to tPA-induced reperfusion, greater incidence of reperfusion and increased the magnitude of femoral artery blood flow achieved after effective thrombolysis. Furthermore, pretreatment with
CGS 13080 resulted in a greater than 10-fold enhancement in the effective dose of tPA. These data indicate that
thromboxane synthase inhibition may be beneficial as an adjunct to
thrombolytic therapy with tPA.