Ultrasound-enhanced thrombolysis

Abstract

Problems with current thrombolytic therapy include slow and incomplete thrombolysis and frequent bleeding complications. Increasing evidence from in vitro, animal, and initial patient studies indicates that application of ultrasound as an adjunct to thrombolytic therapy offers unique potential to improve effectiveness and decrease bleeding complications. Numerous studies in vitro demonstrate that low intensity ultrasound increases enzymatic fibrinolysis through mechanisms that include improving drug transport, reversibly altering fibrin structure, and increasing tPA binding to fibrin. These observations have been confirmed in animal models that demonstrated that ultrasound delivered transcutaneously or with an endovascular catheter accelerates thrombolysis in models of venous, arterial, and small vessel thrombosis. Ultrasound delivered at higher intensities using either an endovascular vibrating wire or transcutaneously in conjunction with stabilized microbubbles can cause mechanical fragmentation of thrombus without administration of plasminogen activator. Recent studies indicate that ultrasound at lower frequencies in the range of 20-40 kHz has a greater effect on thrombolysis with improved tissue penetration and less heating. These studies form the basis for clinical trials investigating the potential of ultrasound as an adjunct to improve thrombolytic therapy.