Enhancing thrombolytic therapy in Japan-dwelling Japanese using clinical ultrasound with microbubble contrast agent

To determine in vitro the efficacy and safety of thrombolysis in blood from Japanese subjects using standard diagnostic ultrasound (US) with or without microbubbles.

Blood from six healthy Japan-dwelling Japanese (mean age 22.3 years), who have relatively low susceptibility to thrombosis because of heredity and dietary habits, was left at room temperature for 24 or 72 h. Each clot-containing well was submerged in a 150-mL heparin-physiologic saline bath (5 units heparin/mL) and rotated at 180 rpm. The 30-min US treatment conditions were: (1) no US or microbubbles; (2) grayscale US (4.5 MHz); (3) color Doppler; (4) grayscale US with addition of 4-μL perflubutane microbubbles (Sonazoid; GE Healthcare Pharma Corporation, Tokyo Japan) to the bath every 5 min; and (5) color Doppler with microbubble addition as above. The Aplio i800 (Canon Medical Systems, Tochigi Japan) US system was used with the i8CX1 transducer.

Among six subjects with clots, the number of 24-h clots that changed to hypoechoic under each condition was as follows: (1) 0, (2) 3, (3) 5, (4) 6, and (5) 5. For 72-h clots, the number of changes was: (1) 0, (2) 1, (3) 3, (4) 6, and (5) 3. In Masson's trichrome-stained specimens, US treatment generated less fibrin within the light-blue amorphous element than in the control. No rupture of red blood cells was observed.

We confirmed that standard clinical diagnostic US, used for grayscale or color Doppler imaging, enhanced thrombolysis. Thrombolytic efficacy was greater with combination of Sonazoid and US than with US alone.