Aprotinin: an antidote for recombinant tissue-type plasminogen activator (rt-PA) active in vivo

The goal of the study was to assess if aprotinin, a protease inhibitor, could be used to antagonize in vivo the effects of recombinant tissue-type plasminogen activator (rt-PA). The time course of the lysis of a radioactive jugular vein thrombus was monitored continuously with an external gamma counter in anesthetized rabbits. Recombinant t-PA (0.25 mg) was given intravenously as a bolus injection (10% of the dose), followed by a 4 h infusion (90% of the dose). Rabbits received aprotinin 20 min after the start of the infusion as an intravenous bolus injection at a dose of 60,000 IU/kg (n = 4) or 20,000 IU/kg (n = 4). The rate of lysis in the different groups was compared 2, 60 and 180 min after aprotinin administration. Both doses of aprotinin immediately stopped thrombolysis. Thrombolysis was still blocked at 180 min with the highest dose but not with the lowest dose. Moreover, aprotinin could prevent the increase in bleeding time secondary to the injection of rt-PA. These results suggest that aprotinin might be used in vivo as an antidote for rt-PA.