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Published on: June 4, 2021
Ultrasound enhancement of thrombolytic therapy: observations and mechanisms
1The Heart Institute, E Wolfson Medical Center Holon, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Insights
Ultrasound therapy can accelerate fibrinolysis, the process of breaking down blood clots, potentially reducing the need for higher drug doses. This non-thermal method enhances clot permeability, improving the effectiveness of clot-busting medications.
Area of Science:
- Cardiovascular Medicine
- Biomedical Engineering
- Hematology
Background:
- Fibrinolytic therapy is crucial for reperfusion during myocardial infarction, but bleeding complications are a concern.
- Myocardial muscle loss is directly related to ischemic duration.
- Adjuvant therapies are sought to improve fibrinolysis efficacy and reduce drug dosage.
Purpose of the Study:
- To investigate the potential of ultrasound as an adjuvant therapy to enhance fibrinolysis.
- To determine if ultrasound can accelerate clot lysis and reduce required lytic agent concentrations.
- To elucidate the mechanism of ultrasound-mediated acceleration of thrombolysis.
Main Methods:
- Noninvasive ultrasound at low intensities and high frequencies was applied to fibrin and whole blood clots in vitro and in vivo.
- Ultrasound effects on clot structure, degradation products, and flow were analyzed.
- The influence of echo-contrast agents on ultrasound-enhanced thrombolysis was assessed.
Main Results:
- Ultrasound significantly accelerated the rate of fibrinolysis in both pure fibrin and whole blood clots.
- The enhancement of fibrinolysis by ultrasound was independent of the specific lytic drug used.
- Ultrasound acted via a nonthermal mechanism, increasing clot permeability and flow without mechanical fragmentation.
- Echo-contrast agents further accelerated ultrasound-mediated thrombolysis.
Conclusions:
- Noninvasive ultrasound is a promising adjuvant therapy for accelerating fibrinolysis.
- Ultrasound enhances thrombolysis by altering fibrin ultrastructure and increasing clot permeability.
- This approach may allow for reduced lytic agent concentrations, potentially mitigating bleeding risks.
Abstract:
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.
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