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Locally targeted cytoprotection with dextran sulfate attenuates experimental porcine myocardial ischaemia/reperfusion injury

Banz, Yara ; Hess, Otto M. ; Robson, Simon C. ; Mettler, Daniel ; Meier, Pascal ; Haeberli, André ; Csizmadia, Eva ; Korchagina, Elena Y. ; Bovin, Nicolai V. ; Rieben, Robert

In: European Heart Journal, 2005, vol. 26, no. 21, p. 2334-2343

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    Titre
    • Locally targeted cytoprotection with dextran sulfate attenuates experimental porcine myocardial ischaemia/reperfusion injury
    Auteur
    • Banz, Yara. Department of Clinical Research, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland
    • Hess, Otto M.. Department of Cardiology, Swiss Cardiovascular Center, University Hospital, Bern, Switzerland
    • Robson, Simon C.. Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
    • Mettler, Daniel. Department of Clinical Research, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland
    • Meier, Pascal. Department of Cardiology, Swiss Cardiovascular Center, University Hospital, Bern, Switzerland
    • Haeberli, André. Department of Clinical Research, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland
    • Csizmadia, Eva. Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
    • Korchagina, Elena Y.. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
    • Bovin, Nicolai V.. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
    • Rieben, Robert. Department of Clinical Research, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • European Heart Journal, 2005, vol. 26, no. 21, p. 2334-2343. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:291642
    Summary
    Aims Intravascular inflammatory events during ischaemia/reperfusion injury following coronary angioplasty alter and denudate the endothelium of its natural anticoagulant heparan sulfate proteoglycan (HSPG) layer, contributing to myocardial tissue damage. We propose that locally targeted cytoprotection of ischaemic myocardium with the glycosaminoglycan analogue dextran sulfate (DXS, MW 5000) may protect damaged tissue from reperfusion injury by functional restoration of HSPG. Methods and results In a closed chest porcine model of acute myocardial ischaemia/reperfusion injury (60 min ischaemia, 120 min reperfusion), DXS was administered intracoronarily into the area at risk 5 min prior to reperfusion. Despite similar areas at risk in both groups (39±8% and 42±9% of left ventricular mass), DXS significantly decreased myocardial infarct size from 61±12% of the area at risk for vehicle controls to 39±14%. Cardioprotection correlated with reduced cardiac enzyme release creatine kinase (CK-MB, troponin-I). DXS abrogated myocardial complement deposition and substantially decreased vascular expression of pro-coagulant tissue factor in ischaemic myocardium. DXS binding, detected using fluorescein-labelled agent, localized to ischaemically damaged blood vessels/myocardium and correlated with reduced vascular staining of HSPG. Conclusion The significant cardioprotection obtained through targeted cytoprotection of ischaemic tissue prior to reperfusion in this model of acute myocardial infarction suggests a possible role for the local modulation of vascular inflammation by glycosaminoglycan analogues as a novel therapy to reduce reperfusion injury