| Evaluation of multimeric tyrosine-O-sulfate as a cytoprotectant in an in vivo model of acute myocardial infarction in pigs. | |
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MedLine Citation:
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PMID: 22398380 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Intracoronary administration of glycosaminoglycan analogs, including the complement inhibitor dextran sulfate, attenuates myocardial ischemia/reperfusion injury (I/R injury). However, dextran sulfate has a distinct anticoagulatory effect, possibly limiting its use in specific situations in vivo. We therefore developed multimeric tyrosine sulfate (sTyr-PAA), a novel, minimally anticoagulatory, fully synthetic non-carbohydrate-containing polyacrylamide conjugate, for in vivo testing in an acute closed-chest porcine model of acute myocardial infarction. METHODS: Following balloon occlusion of the left anterior descending artery just after the first diagonal branch (60-minute ischemia), sTyr-PAA (approx. 10 mg/kg bodyweight, fraction with strongest complement-inhibitory and minimal anticoagulatory properties, n = 11) or phosphate-buffered saline (controls, n = 9) was administered intracoronarily into ischemic myocardium prior to 120 min of reperfusion. RESULTs: sTyr-PAA significantly reduced infarct size (from 61.0 ± 12.0% of the ischemic area at risk to 39.4 ± 17.0%), plasma creatine kinase, local complement deposition and tissue factor upregulation, without affecting systemic coagulation. Protection was associated with significantly reduced myocardial neutrophil extravasation and translated into a significant improvement of ejection fraction and left ventricular enddiastolic pressure. CONCLUSIONs: sTyr-PAA protected significantly against myocardial I/R injury without substantially affecting systemic coagulation. Local intravascular sTyr-PAA administration may prove advantageous in situations where bleeding complications are likely or are to be avoided at all costs. |
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Authors:
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Yara Banz; Otto M Hess; Pascal Meier; Elena Y Korchagina; Elena A Gordeeva; Simon C Robson; Thusitha Gajanayake; Eva Csizmadia; Daniel Mettler; André Haeberli; Nicolai V Bovin; Robert Rieben |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-03-02 |
Journal Detail:
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Title: Cardiology Volume: 121 ISSN: 1421-9751 ISO Abbreviation: Cardiology Publication Date: 2012 |
Date Detail:
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Created Date: 2012-03-21 Completed Date: 2012-05-14 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 1266406 Medline TA: Cardiology Country: Switzerland |
Other Details:
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Languages: eng Pagination: 59-70 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 S. Karger AG, Basel. |
Affiliation:
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Institute of Pathology, University of Bern, Bern, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anticoagulants / pharmacology* Complement Inactivating Agents / pharmacology* Complement Pathway, Classical / drug effects Cytoprotection / drug effects Dose-Response Relationship, Drug Granulocytes / pathology Hemodynamics / drug effects Myocardial Infarction / complications*, immunology Myocardial Reperfusion Myocardial Reperfusion Injury / immunology, pathology, prevention & control* Neutrophils / pathology Sus scrofa Thromboplastin / metabolism Tyrosine / analogs & derivatives*, pharmacology Ventricular Fibrillation / chemically induced |
| Chemical | |
Reg. No./Substance:
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0/Anticoagulants; 0/Complement Inactivating Agents; 55520-40-6/Tyrosine; 9035-58-9/Thromboplastin; 956-46-7/tyrosine O-sulfate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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