Effect of 40-kHz Ultrasound on Acute Thrombotic Ischemia in a Rabbit Femoral Artery Thrombosis Model

Abstract

Background —We have shown previously that 40-kHz ultrasound (US) at low intensity accelerates fibrinolysis in vitro with little heating and good tissue penetration. These studies have now been extended to examine the effects of 40-kHz US on thrombolysis and tissue perfusion in a rabbit model. Methods and Results —Treatment was administered with either US alone at 0.75 W/cm 2 , streptokinase alone, or the combination of US and streptokinase. US or streptokinase resulted in minimal thrombolysis, but reperfusion was nearly complete with the combination after 120 minutes. US also reversed the ischemia in nonperfused muscle in the absence of arterial flow. Tissue perfusion decreased after thrombosis from 13.7±0.2 to 6.6±0.8 U and then declined further to 4.5±0.4 U after 240 minutes. US improved perfusion to 10.6±0.5 and 12.1±0.5 U after 30 and 60 minutes, respectively. This effect was reversible and declined to pretreatment values after US was discontinued. Similarly, tissue pH declined from normal to 7.05±0.02 after thrombosis, but US improved pH to 7.34±0.03 after 60 minutes. US-induced improvement in tissue perfusion and pH also occurred after femoral artery ligation, indicating that thrombolysis did not cause these effects. Conclusions —40-kHz US at low intensity markedly accelerates fibrinolysis and also improves tissue perfusion and reverses acidosis, effects that would be beneficial in treatment of acute thrombosis.

Correlation of cavitation with ultrasound enhancement of thrombolysis

“…The addition of ultrasound with clinically relevant intensities and frequencies has enhanced the enzymatic rate of thrombolytic therapy in vitro (Blinc et al 1993;Francis et al 1992;Holland et al 2002;Lauer et al 1992;Olsson et al 1994;Shaw et al 2001), in animal models (Kashyap et al 1994;Lou et al 1996;Suchkova et al 2000) and in clinical trials (Alexandrov et al 2004a(Alexandrov et al ,2004b. Acceleration of thrombolysis is a particularly critical issue for acute treatment of ischemic stroke.…”

Early iNOS impairment and late eNOS enhancement during reperfusion following 2.49 MHz continuous ultrasound exposure after ischemia

“…In summary attenuation of IR induced tissue damage by ultrasound exposure and NO production has previously been reported following acute ischemic stroke [1], femoral thrombosis [38], muscular ischemia [39], and complete vascular occlusion [7,16], mitigating injury and preventing further tissue damage. The present study extends our understanding of the underlying pathophysiological basis of the damage produced in the microcirculation by IR injury, and how this is mitigated by the application of ultrasound irradiation.…”

Safety and efficacy of sonothrombolysis using bilateral TCD monitoring by diagnostic 2 MHz probes - a pilot study

“…1,2,4,6,14,[20][21][22][23] ), the effect of TCD monitoring in acute IS patients was reported for the first time in 2000 (ref. 24 ) and the results of the first randomized study, testing the effect of sonothrombolysis showed the safety and efficacy of sonothrombolysis using the diagnostic 2-MHz TCD probe 7 .…”

“…Firstly, mechanical effect caused by the thrombus vibration may lead to the acceleration of the penetration of fibrinolytics 3 . Secondly, non-thermal mechanisms -increasing the transport of fibrinolytic agents into the thrombus by mechanical disruption of its structure 24 , direct activation of fibrinolytic enzymes 14,15 , transient peripheral vasodilatation caused probably by increased production of nitrite oxide in the endothelium 21,26 also play a role in clot dissolution. However, confirmation of different effects on thrombus dissolution using various ultrasound frequencies and intensities are still missing.…”