Ultrasound Reversibly Disaggregates Fibrin Fibers

Abstract

SummaryUltrasound accelerates fibrinolysis in vitro and in vivo, primarily through non-thermal mechanisms including cavitation. We have previously observed that ultrasound reversibly increases flow through fibrin gels, a property primarily determined by the structure of the fibrin matrix. Therefore, the effect of ultrasound on the ultrastructure of fibrin gels was examined using scanning electron microscopy. Non-cross- linked fibrin gels were fixed and prepared for microscopy before, during and after exposure to 1 MHz ultrasound, and quantitative analysis of fiber population density and diameter was performed. Gels exposed and fixed in the presence of ultrasound exhibited an increase in density of 65 ± 26% (mean ± SD) at 4 W/cm2 (p <0.000001) accompanied by a decrease in fiber diameter of 27 ± 9% (p <0.000001). Gels fixed 15 min following ultrasound exposure showed no significant change in either density or diameter compared to unexposed gels, indicating that the ultrasound-induced change in fiber structure was reversible. Factor XIII-crosslinked fibrin gels exhibited no change in population density or diameter when exposed to ultrasound. These results indicate that ultrasound exposure causes reversible disaggregation of uncrosslinked fibrin fibers into smaller fibers, an effect that may alter flow resistance and create additional binding sites for fibrinolytic components, improving fibrinolytic efficacy.

Ultrasound Accelerates Thrombolysis of Acutely Induced Platelet-Rich Thrombi Similar to Those in Acute Myocardial Infarction

“…Several in vitro studies suggest that US directly changes the fibrin structure, inducing the better penetration of tPA into the thrombus. 30,31 In the present study, we demonstrated that US enhanced the pharmacological lysis of platelet-rich thrombus, probably without direct influence on the structure of thrombus, indicated by the angiographic and histological data for the US alone group. Therefore, we consider that US accelerates the mixing of tPA into the thrombus in vivo by microstreaming.…”

Pulsed-high intensity focused ultrasound enhanced tPA mediated thrombolysis in a novel in vivo clot model, a pilot study

“…This mechanism would seem to explain the enhancing effect of pulsed-HIFU on tPA-mediated thrombolysis observed in our in vitro [17] study, and similarly could explain the results in the present study. These results are supported by additional studies in purified fibrin gels, where ultrasound exposures caused reversible fiber disaggregation [23], and consequently improved fluid flow through the gels [24]. When the same exposures were carried out in blood clots, improved penetration of tPA was observed, in comparison to untreated clots [25].…”

US-accelerated catheter-directed thrombolysis for the treatment of deep venous thrombosis

“…High-frequency, low-intensity US can be used safely in many medical applications but has no lytic effect. However, the combination of directed US with the local administration of thrombolytic agents accelerates the thrombolytic process (24).…”