Ultrasound-Enhanced Thrombolysis

Abstract

See related article, pages 1470–1475. Intravenous tissue plasminogen activator (tPA) infusion is the fastest and easiest way to initiate reperfusion therapy in acute stroke. However, poor recovery can still be expected in up to 50% of patients, likely as a result of the initial severity of ischemic insult and slow and incomplete thrombolysis.1,2 Clinical improvement and functional independence after stroke usually occur after arterial recanalization.3–6 A recent meta-analysis showed that recanalization is associated with a 4- to 5-fold increase in the odds of a good final functional outcome and a 4- to 5-fold reduction in the odds of death.7 These results lend strong support to the hypothesis that recanalization is the mechanism of how systemic tPA increases the likelihood of recovery from stroke and the use of recanalization as a surrogate end point in phase II trials of reperfusion agents in acute ischemic stroke. Over the past 30 years, in vitro and animal studies have provided evidence that thrombolysis with tPA can be enhanced with ultrasound. Although the mechanisms are still not fully understood, it is known that ultrasound accelerates enzymatic fibrinolysis primarily through nonthermal mechanisms by increasing transport of drug molecules into the clot.8,9 Mechanical effects of ultrasound radiation forces have the ability to influence drug transport. In addition, ultrasound can promote the motion of fluid through and around the …