| Potentiating intra-arterial sonothrombolysis for acute ischemic stroke by the addition of the ultrasound contrast agents (Optison™ & SonoVue(®)). | |
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MedLine Citation:
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PMID: 20473551 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Transcranial ultrasound in combination with intravenously administered ultrasound contrast agents (UCA) in the presence or absence of recombinant tissue plasminogen activator (rt-PA) has been widely evaluated as a new modality for treatment of ischemic stroke. Despite the successful demonstration of accelerated clot lysis there are inherent limitations associated with this modality such as inconsistency in temporal window thickness and/or potential serious cardiopulmonary reactions to intravenous administration of UCA that prevent broad application to ischemic stroke populations. As a complementary modality, we evaluated potential lysis enhancement by intra-arterial ultrasound with concurrent intra-clot delivery of UCA and rt-PA. To this end, clots were formed with average pore diameter similar to clinically retracted clots by adjusting the thrombin concentration. Physical characteristic and retention of UCA after delivery through the catheter as a function of clinically relevant flow rates of 6, 12, 18 ml/h were determined using a microscopic method. The ability of the UCA employed in this study, Optison and SonoVue, to penetrate into the clot was verified using ultrasound B-mode imaging. Clot lysis as a function of rt-PA concentration, 0.009 through 0.5 mg/ml, in the presence and absence of UCA diluted to 1:10, 1:100, and 1:200 v/v at two Peak rarefaction acoustic pressures of 1.3 and 2.1 MPa were evaluated using a weighing method. The study results suggest the addition of only 0.02 ml of 1:100 diluted UCA to rt-PA of 0.009, 0.05, 0.3, and 0.5 mg/ml can enhance the lysis rate by 3.9, 2.6, 1.9 and 1.8 fold in the presence of peak rarefaction acoustic pressure of 1.3 MPa and by 5.1, 3.4, 2.6, 3.1 in the presence of peak rarefaction acoustic pressure of 2.1 MPa, respectively. In addition, Optison and SonoVue demonstrated comparable effectiveness in enhancing the clot lysis rate. Addition of UCA to intra-arterial sonothrombolysis could be considered as a viable treatment option for ischemic stroke patients. |
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Authors:
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Azita Soltani; Ruchi Singhal; Melissa Obtera; Ronald A Roy; Wayne M Clark; Douglas R Hansmann |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of thrombosis and thrombolysis Volume: 31 ISSN: 1573-742X ISO Abbreviation: J. Thromb. Thrombolysis Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-07 Completed Date: 2011-04-20 Revised Date: 2012-01-04 |
Medline Journal Info:
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Nlm Unique ID: 9502018 Medline TA: J Thromb Thrombolysis Country: Netherlands |
Other Details:
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Languages: eng Pagination: 71-84 Citation Subset: IM |
Affiliation:
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Research and Development Department, EKOS Corporation, 11911 North Creek Parkway South, Bothell, WA 98011, USA. asoltani@ekoscorp.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Albumins
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pharmacology* Brain Ischemia* / therapy, ultrasonography Contrast Media / pharmacology* Fibrinolytic Agents / pharmacology* Fluorocarbons / pharmacology* Humans Microbubbles* Models, Cardiovascular* Phospholipids / pharmacology* Stroke* / therapy, ultrasonography Sulfur Hexafluoride / pharmacology* Thrombolytic Therapy / methods* Tissue Plasminogen Activator / pharmacology* Ultrasonography, Doppler, Transcranial / instrumentation, methods* |
| Grant Support | |
ID/Acronym/Agency:
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5R21NS053418-02/NS/NINDS NIH HHS; R21 NS053418-02/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Albumins; 0/Contrast Media; 0/FS 069; 0/Fibrinolytic Agents; 0/Fluorocarbons; 0/Phospholipids; 0/contrast agent BR1; 2551-62-4/Sulfur Hexafluoride; EC 3.4.21.68/Tissue Plasminogen Activator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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