Rationale for Bolus rt-PA Administration
Theoretically, one way to improve thrombolysis is to reach a higher concentration of the lytic agent in the vicinity of the thrombus. The efficacy of intra-arterially administered thrombolytic agents in coronary or peripheral artery obstruction is presumably due to the high concentration of plasminogen activators on the surface and inside the occluding thrombus. Since it is not possible to increase the total dose of administered rt-PA because of an unacceptable risk of bleeding, the only possible way to obtain higher peak plasma levels of rt-PA is to shorten the infusion time. The effectiveness and the safety of such an approach are supported by a number of experimental and clinical observations.
In a rabbit jugular vein model with radioactive thrombi, the infusion of 0.6 mg of rt-PA per kilogram of body weight over 15, 30, or 60 min resulted in a significantly higher thrombolytic effect than the infusion of the same dose over 4 h. In addition, the 30-and 15-min rt-PA infusions, in contrast with 1- and 4-h infusions, did not produce significantly more bleeding than a saline infusion and did not cause any reduction in plasma levels of a2-antiplasmin. These findings indicate that a rapid-infusion regimen results in improved thrombolysis with minimal fibrinogeno-lysis and without excessive bleeding.