Prevention of Arteriovenous Shunt Occlusion Using Microbubble and Ultrasound Mediated Thromboprophylaxis

Abstract

BackgroundPalliative shunts in congenital heart disease patients are vulnerable to thrombotic occlusion. High mechanical index (MI) impulses from a modified diagnostic ultrasound (US) transducer during a systemic microbubble (MB) infusion have been used to dissolve intravascular thrombi without anticoagulation, and we sought to determine whether this technique could be used prophylactically to reduce thrombus burden and prevent occlusion of surgically placed extracardiac shunts.Methods and ResultsHeparin‐bonded ePTFE tubular vascular shunts of 4 mm×2.5 cm (Propaten; W.L Gore) were surgically placed in 18 pigs: a right‐sided side‐to‐side arteriovenous (AV, carotid‐jugular) shunt, and a left‐sided arterio‐arterial (AA, carotid‐carotid) interposition shunt in each animal. After shunt implantation, animals were randomly assigned to one of 3 groups. Transcutaneous, weekly 30‐minute treatments (total of 4 treatments) of either guided high MI US+MB (Group 1; n=6) using a 3% MRX‐801 MB infusion, or US alone (Group 2; n=6) were given separately to each shunt. The third group of 6 pigs received no treatments. The shunts were explanted after 4 weeks and analyzed by histopathology to quantify luminal thrombus area (mm2) for the length of each shunt. No pigs received antiplatelet agents or anticoagulants during the treatment period. The median overall thrombus burden in the 3 groups for AV shunts was 5.10 mm2 compared with 4.05 mm2 in AA (P=0.199). Group 1 pigs had significantly less thrombus burden in the AV shunts (median 2.5 mm2) compared with Group 2 (median 5.6 mm2) and Group 3 (median 7.5 mm2) pigs (P=0.006). No difference in thrombus burden was seen between groups for AA shunts.ConclusionTranscutaneous US with intravenous MB is capable of preventing thrombus accumulation in arteriovenous shunts without the need for antiplatelet agents, and may be a method of preventing progressive occlusion of palliative shunts.

Increasing of Blood-Brain Tumor Barrier Permeability through Transcellular and Paracellular Pathways by Microbubble-Enhanced Diagnostic Ultrasound in a C6 Glioma Model

“…Previous studies have demonstrated that microbubbles increase the possibility of acoustic cavitation and cavitation-related vascular damage effects, such as microvascular rupture and petechial hemorrhage (Miller and Gies, 2000a ; Miller and Quddus, 2000b ; Miller, 2007 ), in which microbubbles served as cavitation nuclei to induce cavitation (Miller and Thomas, 1995 ). These vascular effects could be therapeutically useful in thrombolysis and gene or drug delivery (Molina et al, 2006 ; Ferrara et al, 2007 ; Xie et al, 2009 ; Kutty et al, 2014 ; Sato et al, 2015 ; Burgess and Hynynen, 2016 ). Recently, some studies showed that the permeability of the BTB is increased by focused ultrasound and low-frequency ultrasound in the presence of an ultrasound contrast agent (Liu et al, 2006 ; Hynynen, 2008 ; Xia et al, 2012 ; Diaz et al, 2014 ; Aryal et al, 2015 ).…”

Ultrasound-Induced Microbubble Cavitation for the Treatment of Catheterization-Induced Vasospasm

“…Guided high mechanical index (MI) impulses from a diagnostic US system during intravenous microbubble (MB) infusion have the potential to dissolve intravascular thrombi (termed sonothrombolysis) without the need for fibrinolytic therapy. We have previously studied the feasibility of treating deeply located acute intravascular thrombi with US and intravenous MBs 17 , 18 , 19 . The spasm reversal properties of US + systemic MB therapy have not been previously investigated, but diagnostic US-induced MB cavitation has been shown to enhance endothelial nitric oxide (NO) release 20 , 21 .…”