Document Detail


Evaluation of multimeric tyrosine-O-sulfate as a cytoprotectant in an in vivo model of acute myocardial infarction in pigs.
MedLine Citation:
PMID:  22398380     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-02
Journal Detail:
Title:  Cardiology     Volume:  121     ISSN:  1421-9751     ISO Abbreviation:  Cardiology     Publication Date:  2012  
Date Detail:
Created Date:  2012-03-21     Completed Date:  2012-05-14     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  1266406     Medline TA:  Cardiology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  59-70     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Affiliation:
Institute of Pathology, University of Bern, Bern, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
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:
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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