Ultrasound-enhanced thrombolysis

Problems with current thrombolytic therapy include slow and incomplete thro mbolysis and frequent bleeding complications. Increasing evidence from in v itro, animal, and initial patient studies indicates that application of ult rasound as an adjunct to thrombolytic therapy offers unique potential to im prove effectiveness and decrease bleeding complications. Numerous studies i n vitro demonstrate that lour intensity ultrasound increases enzymatic fibr inolysis through mechanisms that include improving drug transport, reversib ly altering fibrin structure, and increasing tPA binding to fibrin. These o bservations have been confirmed in animal models that demonstrated that ult rasound delivered transcutaneously or with an endovascular catheter acceler ates thrombolysis in models of venous, arterial, and small vessel thrombosi s. Ultrasound delivered at higher intensities using either an endovascular vibrating wire or transcutaneously in conjunction with stabilized microbubb les can cause mechanical fragmentation of thrombus without administration o f plasminogen activator. Recent studies indicate that ultrasound at lower f requencies in the range of 20-40 kHz has a greater effect on thrombolysis w ith improved tissue penetration and less heating. These studies form the ba sis for clinical trials investigating the potential of ultrasound as an adj unct to improve thrombolytic therapy.