The synthetic pentasaccharide fondaparinux prevents coronary microvascular injury and myocardial dysfunction in the ischemic heart

David Montaigne; Xavier Marechal; Steve Lancel; Brigitte Decoster; Philippe Asseman; Remi Neviere

doi:10.1160/TH08-04-0230

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(05): 912-919
DOI: 10.1160/TH08-04-0230

Animal Models

Schattauer GmbH

The synthetic pentasaccharide fondaparinux prevents coronary microvascular injury and myocardial dysfunction in the ischemic heart

Authors

David Montaigne^*

¹EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France

²Soins Intensifs Cardiologiques, Hôpital Cardiologique, CHRU Lille, Université de Lille 2, France
Xavier Marechal^*

¹EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France
Steve Lancel

¹EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France
Brigitte Decoster

¹EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France
Philippe Asseman

²Soins Intensifs Cardiologiques, Hôpital Cardiologique, CHRU Lille, Université de Lille 2, France
Remi Neviere

¹EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France

Abstract

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Summary

Fondaparinux is a synthetic pentasaccharide with powerful anticoagulant properties, which may also reduce ischemia-reperfusion (I/R) injury in vivo.However,the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection are unknown.To address this issue, a crystalloid-perfused heart model was used to assess potential effects of fondaparinux on IR-induced heart injury in the absence of blood. Fondaparinux protects the ischemic myocardium independently of its haemostasis effects. Fondaparinux improved post ischemic myocardial contractile performance and tissue damage. These beneficial effects of fondaparinux may be related to the observed reduction in IR-induced oxidative stress and endothelial activation. In addition, fondaparinux altered NADPH oxidase activity and phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting activation of survival signaling pathways. The present study provides novel information by demonstrating that fondaparinux can attenuate inflammatory responses and oxidative stress in connection with IR heart injury. These findings could represent a potential therapeutic strategy for the prevention of myocardial dysfunction.

Keywords

Ischemia reperfusion - heart - reactive oxygen species - heparin

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References

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