Low molecular weight heparin (Fragmin®) prevents early reocclusion following femoral artery thrombolysis with rt-PA in rabbits

Abstract

The purpose of this study was to evaluate the effect of low molecular weight heparin Fragmin on thrombolysis with tissue-type plasminogen activator (rt-PA) and to compare its effect to that of standard heparin. A rabbit thrombosis model was used, consisting of a blood clot produced in an isolated femoral artery segment with superimposed endothelial damage and distal stenosis. Thirty rabbits were randomized to three treatment groups with rt-PA (30 micrograms.kg-1.min-1 for 60 min and no additional therapy), rt-PA with i.v. standard heparin (200 IU.kg-1 bolus and then 70 IU.kg-1 hourly) and rt-PA with s.c. Fragmin (a single dose of 500 IU.kg-1) prior to rt-PA administration. In six of 10 rabbits given rt-PA only, recanalization was observed which was persistent in three. In eight of 10 rabbits given rt-PA with intravenous heparin, reflow was achieved, which was persistent in three. Fragmin resulted in recanalization in eight of 10 rabbits, with persistent patency in each recanalized rabbit. Reflow time was not shortened with either standard heparin or Fragmin compared with rt-PA alone (64 +/- 41, 56 +/- 18, 50 +/- 23 min respectively), (P = 0.7). Persistent reocclusion after reflow was not observed with Fragmin (0/8) but was present with both standard heparin (5/8, P = 0.03 vs Fragmin) and rt-PA alone (3/6, P = 0.05 vs Fragmin). Thus, in the femoral artery of the rabbit, Fragmin, unlike standard heparin, was found to prevent reocclusion following rt-PA thrombolysis.