Coadministration of PTI and tPA significantly improved tPA-induced thrombolysis in a rabbit model without adversely affecting blood pressure or coagulation parameters.
Does coadministration of a TAFIa inhibitor (PTI) with tPA improve thrombolysis compared to tPA alone in a rabbit arterial thrombolysis model?
Inhibition of activated TAFI enhances tPA-induced arterial thrombolysis in a rabbit model without increasing bleeding risk markers, suggesting a novel adjunctive strategy for acute myocardial infarction.
Achieving early, complete, and sustained reperfusion after acute myocardial infarction does not occur in approximately 50% of patients, even with the most potent established thrombolytic therapy. Bleeding is observed with increased concentrations of thrombolytics as well as with adjunctive antithrombotic and antiplatelet agents. A novel approach to enhance thrombolytic therapy is to inhibit the activated form of thrombin-activatable fibrinolysis inhibitor (TAFI), which attenuates fibrinolysis in clots formed from human plasma. Identification of TAFI in rabbit plasma facilitated the development of a rabbit arterial thrombolysis model to compare the thrombolytic efficacy of tissue-plasminogen activator (tPA) alone or with an inhibitor, isolated from the potato tuber (PTI), of activated TAFI (TAFIa). Efficacy was assessed by determining the time to patency, the time the vessel remained patent, the maximal blood flow achieved during therapy, the percentage of the original thrombus, which lysed, the percentage change in clot weight, the net clot accreted, and the release of radioactive fibrin degradation products into the circulation. The results indicate that coadministration of PTI and tPA significantly improved tPA-induced thrombolysis without adversely affecting blood pressure, activated partial thromboplastin time, thrombin clotting time, fibrinogen, or alpha-2-antiplasmin concentrations. The data indicate that inhibitors of TAFIa may comprise novel and very effective adjuncts to tPA and improve thrombolytic therapy to achieve both clot lysis and vessel patency.
Klement et al. (1999) studied Acute myocardial infarction / arterial thrombosis. Potato tuber inhibitor (PTI) of activated TAFI plus tPA vs. tPA alone was evaluated on Thrombolytic efficacy (time to patency, time patent, maximal blood flow, clot lysis percentage). Coadministration of PTI and tPA significantly improved tPA-induced thrombolysis in a rabbit model without adversely affecting blood pressure or coagulation parameters.