Ultrasound enhancement of rabbit femoral artery thrombolysis

Experiments were conducted to evaluate the potential of low-intensity, externally applied ultrasound to accelerate arterial thrombolysis in an animal model and to characterize potential effects of ultrasound exposure on vessel wall morphology. The femoral arteries of 32 rabbits were exposed, a flowprobe was positioned around the vessel, and a stenosis produced with two circumferential silk sutures to reduce flow by 50%. Thrombosis was achieved by injecting thrombin through the cannulated superficial epigastric branch into a 1-cm segment of femoral artery which was isolated for 20 min. Streptokinase was administered intravenously as a 15,000 U/kg bolus followed by an infusion of 15,000 U/kg per h. Ultrasound (1 MHz, 2 W/cm2) was delivered to the thrombosed vessel during streptokinase administration in 17 animals, and 15 control animals received sham ultrasound only. Thrombolysis occurred in nine of 17 (53%) animals receiving both streptokinase and ultrasound, and this was significantly greater than the rate in animals receiving streptokinase alone (2/15, 13%; P=0.025). Ultrasound caused a mean temperature elevation of 4 degrees C in exposed tissues. Light and electron microscopy demonstrated increased platelet accumulation on thrombi in ultrasound-treated vessels compared with controls. Endothelial cell vacuolation was seen by electron microscopy in ultrasound-exposed vessels. The results indicate that externally applied, low-intensity ultrasound can significantly enhance thrombolysis in a rabbit arterial model. Possible adverse effects are minor and include platelet accumulation, temperature elevation and minor endothelial changes. Externally applied ultrasound has potential value as an adjunct to thrombolytic therapy.