Does external ultrasound accelerate thrombolysis? Results from a rabbit model.

Abstract

BACKGROUND Prior in vitro and in vivo studies have reported that external ultrasound accelerates thrombolysis at intensities too low to have a direct effect on clot dissolution in the absence of a thrombolytic agent. The present study was undertaken to examine the ultrasound effect on thrombolysis and reocclusion in a rabbit thrombosis model. METHODS AND RESULTS Blood clots were produced in a femoral artery segment with endothelial damage and distal stenosis. Recombinant tissue-type plasminogen activator (rTPA) was infused at 30 micrograms.kg-1.min-1 for 60 minutes. Femoral artery flow was measured every 5 minutes for 2 hours. Rabbits were randomized to four groups with continuous wave ultrasound on or off with or without intravenous injection of 17 mg/kg aspirin (+US/-US/+Asp/-Asp). Ultrasound frequency and intensity were 1 MHz and 6.3 W/cm2. In seven of eight and five of five rabbits given rTPA and -US/-Asp or -US/+Asp, respectively, reflow was observed, persisting to the end of the observation period. In five of nine and four of five rabbits given rTPA and +US/-Asp or +US/+Asp, reflow was achieved, but persistent reocclusion was subsequently observed in five of five and two of four of these rabbits, respectively. Overall, femoral artery patency was worse and reocclusion occurred more often when ultrasound was added to rTPA (P = .002 by nonparametric ANOVA). However, initial reflow occurred more rapidly with ultrasound exposure (21 +/- 10 and 33 +/- 6 minutes for the +US/+Asp and +US/-Asp groups, respectively) compared with without ultrasound (46 +/- 13 and 74 +/- 14 minutes for the -US/+Asp and -US/-Asp groups, respectively) (P = .03 by ANOVA). CONCLUSIONS Although time to initial reflow was shortened by ultrasound, it was associated with less reperfusion and more reocclusion in this model. A possible explanation for these results is ultrasound-induced platelet activation counterbalancing its thrombolysis-accelerating effect.