Abstract
This study aimed to explore thrombolysis therapy based on ultrasound combined with urokinase and Arg–Gly–Asp sequence (RGDS)-targeted microbubbles by evaluating the histological changes in a thrombotic rabbit model. Forty-two New Zealand rabbits featuring platelet-rich thrombi in the femoral artery were randomized to (n = 6/group): ultrasound alone (US); urokinase alone (UK); ultrasound plus non-targeted microbubbles (US + M); ultrasound plus RGDS-targeted microbubbles (US + R); RGDS-targeted microbubbles plus urokinase (R + UK); ultrasound, non-targeted microbubbles and urokinase (US + M + UK); and ultrasound, RGDS-targeted microbubbles and urokinase (US + R + UK) groups. Diagnostic ultrasound was used transcutaneously over the thrombus for 30 min. We evaluated the thrombolytic effect based on ultrasound thrombi detection, blood flow, and histological observations. Among all study groups, complete recanalization was achieved in the US + R + UK group. Hematoxylin and eosin staining showed that the thrombi were completely dissolved. Scanning electron microscopy examination demonstrated that the fiber network structure of the thrombi was damaged. Transmission electron microscopy showed that the thrombus was decomposed into high electron-dense particles. Histology for von Willebrand factor and tissue factor were both negative in the US + R + UK group. This study revealed that a thrombolytic therapy consisting of diagnostic ultrasound together with RGDS-targeted and urokinase coupled microbubbles.
Highlights
This study aimed to explore thrombolysis therapy based on ultrasound combined with urokinase and Arg–Gly–Asp sequence (RGDS)-targeted microbubbles by evaluating the histological changes in a thrombotic rabbit model
The ultrasound alone (US), US + M, US + R, urokinase alone (UK), or US + M + UK groups showed no recanalization during the 120 min after treatment, while the US + R + UK and R + UK achieved recanalization (Table 2)
Thirty minutes prior to the observation of thrombolysis, a large, high-amplitude wave was observed in the R + UK and US + R + UK groups (Fig. 2), which led to a higher and larger resonance wave after flashing by US in the US + R + UK groups (Fig. 2)
Summary
This study aimed to explore thrombolysis therapy based on ultrasound combined with urokinase and Arg–Gly–Asp sequence (RGDS)-targeted microbubbles by evaluating the histological changes in a thrombotic rabbit model. We evaluated the thrombolytic effect based on ultrasound thrombi detection, blood flow, and histological observations. This study revealed that a thrombolytic therapy consisting of diagnostic ultrasound together with RGDS-targeted and urokinase coupled microbubbles. Practically, urokinase treatment achieves a lower initial recanalization rate than interventional or surgical methods, and is associated with a high incidence of reocclusion and systemic bleeding events that may threaten one’s life, and could lead to worse short- and long-term clinical consequences[2]. We have studied and tested in conjunction with thrombolytic agents to facilitate thrombus disruption in patients cavitational and non-cavitational effects of ultrasound (US) in order to overcome the limitations of conventional urokinase t herapy[3,4,5].
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