European Heart Journal Advance Access originally published online on July 29, 2005
European Heart Journal 2005 26(21):2334-2343; doi:10.1093/eurheartj/ehi421
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Locally targeted cytoprotection with dextran sulfate attenuates experimental porcine myocardial ischaemia/reperfusion injury
1Department of Clinical Research, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland
2Department of Cardiology, Swiss Cardiovascular Center, University Hospital, Bern, Switzerland
3Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
4Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
Received 10 February 2005; revised 3 June 2005; accepted 27 June 2005; online publish-ahead-of-print 29 July 2005.
* Corresponding author. Tel: +41 31 632 9669; fax: +41 31 632 8837. E-mail address: robert.rieben{at}dkf.unibe.ch
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.
Key Words: Ischaemia reperfusion injury • Dextran sulfate • Cytoprotection • Endothelium
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Banz, R. Rieben, C. Zobrist, P. Meier, S. Shaw, J. Lanz, T. Carrel, and P. Berdat Addition of dextran sulfate to blood cardioplegia attenuates reperfusion injury in a porcine model of cardiopulmonary bypass Eur. J. Cardiothorac. Surg., September 1, 2008; 34(3): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Spirig, C. van Kooten, C. Obregon, L. Nicod, M. Daha, and R. Rieben The Complement Inhibitor Low Molecular Weight Dextran Sulfate Prevents TLR4-Induced Phenotypic and Functional Maturation of Human Dendritic Cells J. Immunol., July 15, 2008; 181(2): 878 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Banz, O. M. Hess, S. C. Robson, E. Csizmadia, D. Mettler, P. Meier, A. Haeberli, S. Shaw, R. A. Smith, and R. Rieben Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1 Cardiovasc Res, December 1, 2007; 76(3): 482 - 493. [Abstract] [Full Text] [PDF]
|
|