Abstract
Vascular disease arises through the complications of atherosclerosis, a complex chronic inflammatory condition affecting the arterial circulation. It leads to the development of vascular lesions or atherosclerotic plaques, which manifest as asymmetrical thickenings of the intima of medium to large sized elastic and muscular arteries. A plaque may rupture with high risk of subsequent thrombus mediated acute clinical events such as myocardial infarction and stroke. Focused ultrasound is one of the non- invasive methods to treat abnormal tissues. In pulsed- focused ultrasound with low duty cycle, which is used for thrombolysis, energy deposition rates are low that temperature rises are well below the threshold for thermal damage. The aim of this study was to generate a rabbit model of common carotid artery atherothrombotic stenosis and the subsequent investigating the feasibility of dual- frequency focused ultrasound - mediated thrombolytic therapy accompanied by tissue plasminogen activator (tPA) administration in this model. Briefly, New Zealand white rabbits were submitted to common carotid artery atherothrombotic stenosis by primary balloon injury followed 1.5% cholesterol- rich diet injury for 12 weeks and finally perivascular severe cold injury. Then treatment group underwent dual- frequency focused ultrasound (I= 3w, F= 3MHz, PD= 30 ms and I= 30 W/cm2, F= 150 KHz, PD= 150 ms) - mediated thrombolytic therapy accompanied by tPA (0.6 mg/kg) administration. Results from histopathology, B-mode and color Doppler ultrasonography, showed a significant reduction in the mean value for thrombus content, blood mean velocity and a significant increase in the mean value for blood volume flow at the stenotic region in the treatment group compared with the other groups (P<0.05). Focal thrombus disruption mechanism was partly clarified as originated from microjet formation upon bubble collapse. Enhanced anti- thrombotic effect of tPA, due to microjets- induced by dual- frequency focused ultrasound, can cause to reduce the thrombus content and significantly dilate the luminal cross-sectional area of stenosis and lower treatment time in comparison with conventional tPA thrombolytic therapy.
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