Ultrasound Combined With Continuous Microbubble Injection to Enhance Catheter-Directed Thrombolysis in Vitro and in Vivo

Objectives-To investigate the influence of microbubble perfusion mode on catheter-directed thrombolysis (CDT), we evaluated the effect of two different types of microbubble perfusion modes (continuous injection versus bolus injection) on the thrombolytic efficacy of CDT in vitro and further assessed the effect of continuous microbubble injection on CDT in vivo.Methods-In an in vitro experimental setup, 50 fresh bovine whole blood clots were randomized into five groups: ultrasound and continuous microbubble injection-enhanced CDT (US + cMB + CDT), ultrasound and bolus microbubble injection-enhanced CDT (US + bMB + CDT), US + CDT, US + cMB, and CDT. In a porcine femoral vein thrombosis model, 16 completely obstructive thrombi were randomly assigned to the CDT group and the US + cMB + CDT group, respectively. Thrombolysis rate, vascular recanalization rate, hematoxylin-eosin, and immunofluorescence staining were used to evaluate the thrombolytic effect in vitro and in vivo.Results-In vitro, US + cMB + CDT group resulted in a significantly higher thrombolysis rate compared with the other four groups (P < .05). Meanwhile, this group also demonstrated a looser clot structure and more disrupted fibrin structures. In vivo, US + cMB + CDT contributed to a significantly higher vascular recanalization rate compared with CDT (87.50% versus 25.00%, P < .05).Conclusions-US + cMB + CDT was more effective than US + bMB + CDT in thrombolysis, and ultrasound combined with continuous microbubble injection could enhance the thrombolytic efficacy of CDT.