Shiftman et al investigated the effects of 2 dosing regimens of rt-PA on pulmonary thrombolysis in a canine model of pulmonary embolism that caused pulmonary hypertension. In that study, rt-PA, 1 mg/ kg, was infused over 15 or 90 min. The shorter infusion resulted in a marked increase in the rate of lysis (56%/h vs 27%/h, p<0.001) and was accompanied by a faster and greater decrease in mean pulmonary artery pressure.
Subsequently, the same group compared the effects of a 5-min versus a 15-min administration of rt-PA on the dynamics of thrombolysis and pulmonary pressure-flow. The decrease in pulmonary artery pressure was greater with the 15-min infusion. Although the extent of total clot lysis was not significantly different between regimens, it did tend to be greater with rt-PA infused over 15 min. This study suggests the existence of an upper limit to the dose-thrombolytic rate relation with rt-PA.
Eisenberg and coworkers evaluated the duration of lytic effect of rt-PA and streptokinase in patients with acute myocardial infarction. They evaluated serially cross-linked fibrin degradation products (FDPs) and Bp 15-42 fibrinopeptide (Bp 15-42), 2 specific markers of the lysis of fibrin. Patients receiving rt-PA showed higher plasma levels of both cross-linked FDPs and Bp 15-42 than those receiving streptokinase.