Ultrasound enhancement of thrombolytic therapy: observations and mechanisms.

Fibrinolytic therapy is a proven approach for achieving reperfusion of occluded coronary arteries during myocardial infarction, resulting in reduced mortality and preservation of ventricular function. The amount of myocardial muscle loss is proportional to the duration of ischemia. Bleeding complications are not infrequent. Adjuvant therapy by ultrasound might enhance the rate of fibrinolysis and reduce the concentrations of lytic agents required to achieve an equivalent degree of clot lysis. Noninvasive ultrasound at low intensities and high frequencies, parameters that potentially could be applied and tolerated in vivo, have been proven to significantly accelerate the rate of fibrinolysis in both in vitro and in vivo models, in pure fibrin as well as whole blood clots. Such enhancement is not drug-specific. These effects were achieved by nonthermal mechanism. Ultrasound exposure did not cause mechanical fragmentation of the clot, did not alter the size of plasmatic derivates and degradation products. Ultrasound caused increased flow rate through thrombi, probably by cavitation-induced changes in fibrin ultrastructure; disaggregation of uncrosslinked fibrin fibers into smaller fibers has been shown. This resulted in increased transport of the lytic agent into the clot, alteration of binding affinity and increased maximum binding. Presence of echo-contrast agent induced further acceleration of thrombolysis by ultrasound.