Albumin Microbubble Echo-Contrast Material as an Enhancer for Ultrasound Accelerated Thrombolysis

Abstract

Background Recent findings suggest that acoustic cavitation is responsible for acceleration of thrombolysis by ultrasound (US) energy. It is known that albumin microbubbles lower the threshold of acoustic cavitation production. Methods and Results The present study was designed to determine whether the presence of albumin microbubbles used for echo-contrast material (Albunex) can further accelerate fibrinolysis by US. Artificial thrombus was produced by Chandler’s loop method with blood extracted from a healthy subject. Urokinase (UK, 1200 IU/mL) was added to the artificial thrombi placed in test tubes. Each thrombus was exposed to US (170 kHz) at a distance of 1.2 cm for a total of 60 seconds at an intensity of 0.5 W/cm 2 at intervals of 2 seconds on and 4 seconds off. Echo-contrast material (0.6×10 6 microspheres per mL) or 5% albumin (for control) was circulated near the thrombus at a rate of 1 mL/min during the US exposure. Fibrinolysis was later determined by percentage of weight loss of thrombus after 60 minutes of incubation (n=15). Fibrinolysis with UK alone was 26.6±4.8%. Fibrinolysis with UK+US treatment was 33.3±5.8%. Further increase of fibrinolysis to 51.3±7.7% occurred in the presence of Albunex (UK+US+Albunex). Statistical differences were obtained between all these groups (ANOVA). Conclusions The presence of the echo-contrast agent induced further acceleration of thrombolysis by US energy. It is suggested that this diagnostic echo-contrast material can be used as an alternative therapeutic US drug enhancer for thrombolysis.