| Thrombolysis with plasmin: implications for stroke treatment. | |
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MedLine Citation:
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PMID: 20876504 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Plasmin is a direct-acting thrombolytic agent with a striking hemostatic safety advantage over plasminogen activators in animal models of thrombolysis and bleeding. In contradistinction to plasminogen activators, which risk bleeding at any effective thrombolytic dose, plasmin is tolerated without bleeding at several-fold higher amounts than those needed for thrombolysis. Plasmin has been safe in a current trial in patients with peripheral arterial or graft occlusion, and efforts are now directed toward therapy of stroke caused by cerebral artery occlusion. A rabbit (4 kg body weight) model of 2-hour, thrombin-induced middle cerebral artery occlusion using angiographic documentation of vascular patency and recanalization was used to perform a dose-ranging study of plasmin, delivered by catheter over a median duration of 10 minutes. Plasmin induced early recanalization in all animals (3 per group) within 10 minutes after discontinuation of 3, 2, or 1 mg of agent infusion. Control saline infusion failed to induce recanalization in 3 of 3 subjects. Plasmin rapidly induces middle cerebral artery recanalization, as determined in an angiogram-based animal model of arterial occlusion. Based on these data and other information, a phase I/IIa clinical trial of plasmin in human middle cerebral artery ischemic stroke has been initiated. |
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Authors:
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Victor J Marder; Reza Jahan; Theresa Gruber; Abha Goyal; Vik Arora |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Stroke; a journal of cerebral circulation Volume: 41 ISSN: 1524-4628 ISO Abbreviation: Stroke Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-29 Completed Date: 2010-11-01 Revised Date: 2011-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0235266 Medline TA: Stroke Country: United States |
Other Details:
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Languages: eng Pagination: S45-9 Citation Subset: IM |
Affiliation:
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Division of Hematology-Oncology, David Geffen School of Medicine at University of California Los Angeles, Room A3-29 Rehabilitation Building, 1000 Veteran Ave, Los Angeles, CA 90095, USA. vmarder@mednet.ucla.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Disease Models, Animal Fibrinolysin / therapeutic use* Fibrinolytic Agents / therapeutic use Infarction, Middle Cerebral Artery / drug therapy* Rabbits Stroke / drug therapy* Thrombolytic Therapy / methods* Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
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P50 NS044378/NS/NINDS NIH HHS; P50 NS044378-08/NS/NINDS NIH HHS; R01 HL074051/HL/NHLBI NIH HHS; R01 HL074051-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fibrinolytic Agents; EC 3.4.21.7/Fibrinolysin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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