Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model

Abstract Adjuvant ultrasound at 2 MHz with or without an ultrasound contrast agent improves the rate of thrombus resolution by recombinant tissue plasminogen activator (rt-PA) in laboratory and clinical studies. A sub-megahertz approach can further expand this therapy to a subset of patients with an...

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Autores principales:	Robert T. Kleven, Kunal B. Karani, Nicole Hilvert, Samantha M. Ford, Karla P. Mercado-Shekhar, John M. Racadio, Marepalli B. Rao, Todd A. Abruzzo, Christy K. Holland
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/194cf381637f4fa18334d3a7647f19d8
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spelling	oai:doaj.org-article:194cf381637f4fa18334d3a7647f19d82021-12-02T14:04:38ZAccelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model10.1038/s41598-021-83442-32045-2322https://doaj.org/article/194cf381637f4fa18334d3a7647f19d82021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83442-3https://doaj.org/toc/2045-2322Abstract Adjuvant ultrasound at 2 MHz with or without an ultrasound contrast agent improves the rate of thrombus resolution by recombinant tissue plasminogen activator (rt-PA) in laboratory and clinical studies. A sub-megahertz approach can further expand this therapy to a subset of patients with an insufficient temporal bone window, improving efficacy in unselected patient populations. The aim of this study was to determine if a clinical ultrasound contrast agent (UCA), Definity, and 220 kHz pulsed ultrasound accelerated rt-PA thrombolysis in a preclinical animal model of vascular occlusion. The effect of Definity and ultrasound on thrombus clearance was first investigated in vitro and subsequently tested in a xenographic porcine cerebral thromboembolism model in vivo. Two different microcatheter designs (end-hole, multi-side-hole) were used to infuse rt-PA and Definity at the proximal edge or directly into clots, respectively. Sonothrombolysis with Definity increased clot mass loss relative to saline or rt-PA alone in vitro, only when rt-PA was administered directly into clots via a multi-side-hole microcatheter. Combined treatment with rt-PA, Definity, and ultrasound in vivo increased the rate of reperfusion up to 45 min faster than clots treated with rt-PA or saline. In this porcine cerebral thromboembolism model employing retracted human clots, 220 kHz ultrasound, in conjunction with Definity increased the probability of early successful reperfusion with rt-PA.Robert T. KlevenKunal B. KaraniNicole HilvertSamantha M. FordKarla P. Mercado-ShekharJohn M. RacadioMarepalli B. RaoTodd A. AbruzzoChristy K. HollandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robert T. Kleven Kunal B. Karani Nicole Hilvert Samantha M. Ford Karla P. Mercado-Shekhar John M. Racadio Marepalli B. Rao Todd A. Abruzzo Christy K. Holland Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model
description	Abstract Adjuvant ultrasound at 2 MHz with or without an ultrasound contrast agent improves the rate of thrombus resolution by recombinant tissue plasminogen activator (rt-PA) in laboratory and clinical studies. A sub-megahertz approach can further expand this therapy to a subset of patients with an insufficient temporal bone window, improving efficacy in unselected patient populations. The aim of this study was to determine if a clinical ultrasound contrast agent (UCA), Definity, and 220 kHz pulsed ultrasound accelerated rt-PA thrombolysis in a preclinical animal model of vascular occlusion. The effect of Definity and ultrasound on thrombus clearance was first investigated in vitro and subsequently tested in a xenographic porcine cerebral thromboembolism model in vivo. Two different microcatheter designs (end-hole, multi-side-hole) were used to infuse rt-PA and Definity at the proximal edge or directly into clots, respectively. Sonothrombolysis with Definity increased clot mass loss relative to saline or rt-PA alone in vitro, only when rt-PA was administered directly into clots via a multi-side-hole microcatheter. Combined treatment with rt-PA, Definity, and ultrasound in vivo increased the rate of reperfusion up to 45 min faster than clots treated with rt-PA or saline. In this porcine cerebral thromboembolism model employing retracted human clots, 220 kHz ultrasound, in conjunction with Definity increased the probability of early successful reperfusion with rt-PA.
format	article
author	Robert T. Kleven Kunal B. Karani Nicole Hilvert Samantha M. Ford Karla P. Mercado-Shekhar John M. Racadio Marepalli B. Rao Todd A. Abruzzo Christy K. Holland
author_facet	Robert T. Kleven Kunal B. Karani Nicole Hilvert Samantha M. Ford Karla P. Mercado-Shekhar John M. Racadio Marepalli B. Rao Todd A. Abruzzo Christy K. Holland
author_sort	Robert T. Kleven
title	Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model
title_short	Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model
title_full	Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model
title_fullStr	Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model
title_full_unstemmed	Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model
title_sort	accelerated sonothrombolysis with definity in a xenographic porcine cerebral thromboembolism model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/194cf381637f4fa18334d3a7647f19d8
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Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model

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