Quantification of microbubble‐induced sonothrombolysis in an ex vivo non‐human primate model
Background In vitro studies with ultrasound (US) and microbubbles (MB) have reported that sono‐thrombolysis can be achieved at high peak rarefactional acoustic pressure amplitudes (PRAPAs) using 0.25 and 1.05 MHz US frequencies. Objective The aim of the current study was to determine if these parame...
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| Veröffentlicht in: | Journal of thrombosis and haemostasis 2021-02, Vol.19 (2), p.502-512 |
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| creator | Hinds, Monica T. Ammi, Azzdine Y. Johnson, Jennifer Kaul, Sanjiv |
| description | Background
In vitro studies with ultrasound (US) and microbubbles (MB) have reported that sono‐thrombolysis can be achieved at high peak rarefactional acoustic pressure amplitudes (PRAPAs) using 0.25 and 1.05 MHz US frequencies.
Objective
The aim of the current study was to determine if these parameters work on an ex vivo physiological model of thrombosis.
Methods
A thrombogenic device was placed in an ex vivo chronic arteriovenous shunt in juvenile baboons. Platelet accumulation was measured by dynamic imaging of the device and the 10 cm thrombus tail with 111In‐labeled platelets. After 15 minutes of thrombus formation, treatment with either low‐dose recombinant tissue plasminogen activator (rtPA) or low‐dose rtPA + MB+US was performed for 20 minutes. Four US settings at 0.25% duty cycle were used: 0.25 MHz at PRAPAs of 1.20 and 2.20 MPa, and 1.05 MHz at 1.75 and 4.75 MPa.
Results
Platelet accumulation was not inhibited by low‐dose rtPA or MB with US alone. Platelet accumulation was significantly reduced with 0.25 MHz US at 2.20 PRAPA (P |
| doi_str_mv | 10.1111/jth.15180 |
| format | Article |
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In vitro studies with ultrasound (US) and microbubbles (MB) have reported that sono‐thrombolysis can be achieved at high peak rarefactional acoustic pressure amplitudes (PRAPAs) using 0.25 and 1.05 MHz US frequencies.
Objective
The aim of the current study was to determine if these parameters work on an ex vivo physiological model of thrombosis.
Methods
A thrombogenic device was placed in an ex vivo chronic arteriovenous shunt in juvenile baboons. Platelet accumulation was measured by dynamic imaging of the device and the 10 cm thrombus tail with 111In‐labeled platelets. After 15 minutes of thrombus formation, treatment with either low‐dose recombinant tissue plasminogen activator (rtPA) or low‐dose rtPA + MB+US was performed for 20 minutes. Four US settings at 0.25% duty cycle were used: 0.25 MHz at PRAPAs of 1.20 and 2.20 MPa, and 1.05 MHz at 1.75 and 4.75 MPa.
Results
Platelet accumulation was not inhibited by low‐dose rtPA or MB with US alone. Platelet accumulation was significantly reduced with 0.25 MHz US at 2.20 PRAPA (P < .001) and with 1.05 MHz at 1.75 MPa and 4.75 MPa (P < .05) when used with MB and low‐dose rtPA. Although this approach prevented platelet accumulation it did not cause thrombolysis on the device.
Conclusions
rtPA + MB + US (0.25 and 1.05 MHz) resulted in inhibition of platelet accumulation on the thrombogenic device when moderately high PRAPAs (≥1.75 MPa) were used. These results taken in context with lytic effects of US on myocardial microthrombi and direct effect on myocardial blood flow and function provide direction for the use of therapeutic US in acute coronary syndromes.</description><identifier>ISSN: 1538-7933</identifier><identifier>ISSN: 1538-7836</identifier><identifier>EISSN: 1538-7836</identifier><identifier>DOI: 10.1111/jth.15180</identifier><identifier>PMID: 33205492</identifier><language>eng</language><publisher>England: Elsevier Limited</publisher><subject>Animals ; Blood clots ; Blood flow ; contrast media ; Microbubbles ; Platelets ; Primates ; t-Plasminogen activator ; Thrombolysis ; Thrombolytic Therapy ; thrombolytics ; Thrombosis ; Thrombosis - therapy ; Tissue Plasminogen Activator ; Ultrasonic Therapy ; Ultrasound</subject><ispartof>Journal of thrombosis and haemostasis, 2021-02, Vol.19 (2), p.502-512</ispartof><rights>2020 International Society on Thrombosis and Haemostasis</rights><rights>2020 International Society on Thrombosis and Haemostasis.</rights><rights>2021 International Society on Thrombosis and Haemostasis</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4430-1d9277434ddc9abc43f06cad3a147d0a26b124f3f7fd6a426c3b2a1d8c2b0aed3</citedby><cites>FETCH-LOGICAL-c4430-1d9277434ddc9abc43f06cad3a147d0a26b124f3f7fd6a426c3b2a1d8c2b0aed3</cites><orcidid>0000-0003-0124-3920</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33205492$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hinds, Monica T.</creatorcontrib><creatorcontrib>Ammi, Azzdine Y.</creatorcontrib><creatorcontrib>Johnson, Jennifer</creatorcontrib><creatorcontrib>Kaul, Sanjiv</creatorcontrib><title>Quantification of microbubble‐induced sonothrombolysis in an ex vivo non‐human primate model</title><title>Journal of thrombosis and haemostasis</title><addtitle>J Thromb Haemost</addtitle><description>Background
In vitro studies with ultrasound (US) and microbubbles (MB) have reported that sono‐thrombolysis can be achieved at high peak rarefactional acoustic pressure amplitudes (PRAPAs) using 0.25 and 1.05 MHz US frequencies.
Objective
The aim of the current study was to determine if these parameters work on an ex vivo physiological model of thrombosis.
Methods
A thrombogenic device was placed in an ex vivo chronic arteriovenous shunt in juvenile baboons. Platelet accumulation was measured by dynamic imaging of the device and the 10 cm thrombus tail with 111In‐labeled platelets. After 15 minutes of thrombus formation, treatment with either low‐dose recombinant tissue plasminogen activator (rtPA) or low‐dose rtPA + MB+US was performed for 20 minutes. Four US settings at 0.25% duty cycle were used: 0.25 MHz at PRAPAs of 1.20 and 2.20 MPa, and 1.05 MHz at 1.75 and 4.75 MPa.
Results
Platelet accumulation was not inhibited by low‐dose rtPA or MB with US alone. Platelet accumulation was significantly reduced with 0.25 MHz US at 2.20 PRAPA (P < .001) and with 1.05 MHz at 1.75 MPa and 4.75 MPa (P < .05) when used with MB and low‐dose rtPA. Although this approach prevented platelet accumulation it did not cause thrombolysis on the device.
Conclusions
rtPA + MB + US (0.25 and 1.05 MHz) resulted in inhibition of platelet accumulation on the thrombogenic device when moderately high PRAPAs (≥1.75 MPa) were used. These results taken in context with lytic effects of US on myocardial microthrombi and direct effect on myocardial blood flow and function provide direction for the use of therapeutic US in acute coronary syndromes.</description><subject>Animals</subject><subject>Blood clots</subject><subject>Blood flow</subject><subject>contrast media</subject><subject>Microbubbles</subject><subject>Platelets</subject><subject>Primates</subject><subject>t-Plasminogen activator</subject><subject>Thrombolysis</subject><subject>Thrombolytic Therapy</subject><subject>thrombolytics</subject><subject>Thrombosis</subject><subject>Thrombosis - therapy</subject><subject>Tissue Plasminogen Activator</subject><subject>Ultrasonic Therapy</subject><subject>Ultrasound</subject><issn>1538-7933</issn><issn>1538-7836</issn><issn>1538-7836</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKAzEYRoMoXqoLX0ACbnTRmtvcNoKIVwoi1HXMbWzKTKKTmWp3PoLP6JMYWysqmE1Ccjh8fz4AdjEa4LiOJu14gBOcoxWwiROa97OcpqvLc0HpBtgKYYIQLhKC1sEGpQQlrCCb4P62E661pVWitd5BX8LaqsbLTsrKvL--Wac7ZTQM3vl23Pha-moWbIDWQeGgeYFTO_XQeRfhcVfHu8fG1qI1sPbaVNtgrRRVMDtfew_cnZ-NTi_7w5uLq9OTYV8xRlEf64JkGaNMa1UIqRgtUaqEpgKzTCNBUokJK2mZlToVjKSKSiKwzhWRSBhNe-B44X3sZG20Mq5tRMXnWZoZ98Ly3y_OjvmDn_I8KXBRoCg4-BI0_qkzoeW1DcpUlXDGd4ETluI8JUmSRHT_DzrxXePieJHKGU4pYThShwsqfmcIjSm_w2DEP3vjsTc-7y2yez_Tf5PLoiJwtACebWVm_5v49ehyofwAkNamhQ</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Hinds, Monica T.</creator><creator>Ammi, Azzdine Y.</creator><creator>Johnson, Jennifer</creator><creator>Kaul, Sanjiv</creator><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0124-3920</orcidid></search><sort><creationdate>202102</creationdate><title>Quantification of microbubble‐induced sonothrombolysis in an ex vivo non‐human primate model</title><author>Hinds, Monica T. ; Ammi, Azzdine Y. ; Johnson, Jennifer ; Kaul, Sanjiv</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4430-1d9277434ddc9abc43f06cad3a147d0a26b124f3f7fd6a426c3b2a1d8c2b0aed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Blood clots</topic><topic>Blood flow</topic><topic>contrast media</topic><topic>Microbubbles</topic><topic>Platelets</topic><topic>Primates</topic><topic>t-Plasminogen activator</topic><topic>Thrombolysis</topic><topic>Thrombolytic Therapy</topic><topic>thrombolytics</topic><topic>Thrombosis</topic><topic>Thrombosis - therapy</topic><topic>Tissue Plasminogen Activator</topic><topic>Ultrasonic Therapy</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hinds, Monica T.</creatorcontrib><creatorcontrib>Ammi, Azzdine Y.</creatorcontrib><creatorcontrib>Johnson, Jennifer</creatorcontrib><creatorcontrib>Kaul, Sanjiv</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hinds, Monica T.</au><au>Ammi, Azzdine Y.</au><au>Johnson, Jennifer</au><au>Kaul, Sanjiv</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantification of microbubble‐induced sonothrombolysis in an ex vivo non‐human primate model</atitle><jtitle>Journal of thrombosis and haemostasis</jtitle><addtitle>J Thromb Haemost</addtitle><date>2021-02</date><risdate>2021</risdate><volume>19</volume><issue>2</issue><spage>502</spage><epage>512</epage><pages>502-512</pages><issn>1538-7933</issn><issn>1538-7836</issn><eissn>1538-7836</eissn><abstract>Background
In vitro studies with ultrasound (US) and microbubbles (MB) have reported that sono‐thrombolysis can be achieved at high peak rarefactional acoustic pressure amplitudes (PRAPAs) using 0.25 and 1.05 MHz US frequencies.
Objective
The aim of the current study was to determine if these parameters work on an ex vivo physiological model of thrombosis.
Methods
A thrombogenic device was placed in an ex vivo chronic arteriovenous shunt in juvenile baboons. Platelet accumulation was measured by dynamic imaging of the device and the 10 cm thrombus tail with 111In‐labeled platelets. After 15 minutes of thrombus formation, treatment with either low‐dose recombinant tissue plasminogen activator (rtPA) or low‐dose rtPA + MB+US was performed for 20 minutes. Four US settings at 0.25% duty cycle were used: 0.25 MHz at PRAPAs of 1.20 and 2.20 MPa, and 1.05 MHz at 1.75 and 4.75 MPa.
Results
Platelet accumulation was not inhibited by low‐dose rtPA or MB with US alone. Platelet accumulation was significantly reduced with 0.25 MHz US at 2.20 PRAPA (P < .001) and with 1.05 MHz at 1.75 MPa and 4.75 MPa (P < .05) when used with MB and low‐dose rtPA. Although this approach prevented platelet accumulation it did not cause thrombolysis on the device.
Conclusions
rtPA + MB + US (0.25 and 1.05 MHz) resulted in inhibition of platelet accumulation on the thrombogenic device when moderately high PRAPAs (≥1.75 MPa) were used. These results taken in context with lytic effects of US on myocardial microthrombi and direct effect on myocardial blood flow and function provide direction for the use of therapeutic US in acute coronary syndromes.</abstract><cop>England</cop><pub>Elsevier Limited</pub><pmid>33205492</pmid><doi>10.1111/jth.15180</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0124-3920</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Blood clots Blood flow contrast media Microbubbles Platelets Primates t-Plasminogen activator Thrombolysis Thrombolytic Therapy thrombolytics Thrombosis Thrombosis - therapy Tissue Plasminogen Activator Ultrasonic Therapy Ultrasound |
| title | Quantification of microbubble‐induced sonothrombolysis in an ex vivo non‐human primate model |
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