ENHANCEMENT OF THROMBOLYSIS BY ULTRASOUND

Drug-induced early reperfusion in acute myocardial infarction reduces myocardial damage and decreases mortality. A further beneficial effect may be achieved if the time from start of thrombolytic treatment to reperfusion, on average 45 min, can be shortened. With this purpose in mind, we have analysed the effect of ultrasound on the reperfusion time in an experimental model in vitro. A cylindrical fibrin thrombus with a 2 mm diameter and a 20 muL volume was made by thrombin activation of a pure 0.5% fibrinogen solution in a soft silicone tube. The tube was placed in a low pressure perfusion system and maintained at 37-degrees-C. The thrombi were then exposed to hydrostatic loading with a streptokinase concentration of 5000 units/mL. Reperfusion times (RT) were measured from time of Streptokinase exposure to fluid passage, identified by the photoelectric technique. RT increased significantly with increasing thrombus age (r = 0.92, p < 0.05) and was 34-45 min (95% confidence limits) at a thrombus age of 1 h and 102-122 min at a thrombus age of 2 h. RT was unaffected by temperatures between 33 and 45-degrees-C but increased with higher temperatures. All investigations of ultrasound effects were performed with 1 h old thrombi and at 37-degrees-C. RT decreased by 49% (p < 0.01) as an effect of exposure to 1 MHz ultrasound at 1 W/cm2 SATA. Intermittent ultrasound exposure for 10 mus/ms with the same intensity and frequency shortened RT by 54% (p < 0.01). 1 MHz ultrasound at 5 W/cm2 prevented the thrombolysis completely, whilst intermittent exposure, 10 mus/ms of 1 MHz at 5 W/cm2, did not significantly effect RT. RT was shortened by 65% as an effect of exposure to ultrasound of 170 kHz and 0.5 W/cm2 intensity. Burst exposure with an intensity of 0.75 W/cm2 and a frequency of 170 kHz reduced RT by 48%. We conclude that ultrasound exposure of a type and intensity that may be transmitted transthoracically accelerates the thrombolytic process under experimental conditions. The potential benefit of this technique clearly motivates further studies.