Acceleration of fibrinolysis by ultrasound in a rabbit ear model of small vessel injury.

High frequency ultrasound has been previously shown to accelerate fibrinolysis in vitro at intensities that are potentially applicable for noninvasive administration clinically. To extend these findings in vivo, we have investigated the effects of ultrasound on fibrinolysis induced by streptokinase in a rabbit model of small vessel injury. Full thickness puncture wounds were made in rabbit ears with a scalpel blade. The rabbits were rested for 2-3 hours after cessation of bleeding to allow maturation of hemostatic plugs. Saline or streptokinase was then infused intravenously, and ultrasound was applied to some lesions at 1 MHz with a 50% duty cycle at 1 W/cm2 net intensity. Ear lesions in rabbits treated with saline showed no bleeding after 30 minutes whether they were exposed to ultrasound or not. Streptokinase alone induced bleeding after 19.7 +/- 5.5 minutes. Application of ultrasound significantly reduced the time to bleeding in streptokinase treated rabbits to 7.5 +/- 3.9 minutes (p < .002). The times to bleeding with "sham" ultrasound (18.8 +/- 5.6 minutes) and heating of the ear (18.0 +/- 5.6 minutes) during streptokinase administration were not significantly different compared to streptokinase alone. Histologic examination revealed that application of ultrasound resulted in a mild increase in interstitial edema and accumulation of polymorphonuclear leukocytes but did not cause vascular or other tissue damage. We conclude that the noninvasive, percutaneous application of ultrasound significantly accelerated streptokinase-induced fibrinolysis in this rabbit model of small vessel injury.