Intravenous Administration of Recombinant Tissue Plasminogen Activator

Optimizing the Rate of Coronary Thrombolysis

¹ From the Department of Medicine, University of Manitoba, and the Section of Cardiology/Health Sciences Centre, Winnipeg, Manitoba, Canada

Although many studies have confirmed the efficacy of thrombolytic therapy in treatment of acute myocardial infarction, few studies have been designed to determine which dose regimen optimizes the rate of coronary thrombolysis. This study was designed to compare the efficacy of coronary thrombolysis obtained with intravenous administration of three dose regimens of recombinant tissue plasminogen activator (rtPA). The same total dose was administered as a bolus, over 30 min, or over 90 min. A canine model was employed. Coronary thrombosis was induced by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, 18 dogs were randomized into 3 groups of 6 dogs each. In group 1 dogs, 0.5 mg/kg of rtPA was administered intravenously as a bolus; in the group 2 dogs, rtPA was administered intravenously over 30 min (rtPA₃₀); in the group 3 dogs, the drug was administered over 90 min (rtPA₉₀). Coronary thrombolysis was assessed with a gamma camera. While at 100 min, the extent of clot lysis was similar between groups, 15 and 30 min after the start of rtPA administration, coronary thrombolysis was significantly less in the rtPA₉₀ group. These results indicate that for a given total dose of rtPA, the rate of intravenous administration may significantly affect the rate of coronary thrombolysis.

Key Words: dosing • recombinant tissue plasminogen activator • thrombolysis

Submitted on April 27, 1994
Accepted on August 14, 2007