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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

David Montaigne   *
1   EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France
2   Soins Intensifs Cardiologiques, Hôpital Cardiologique, CHRU Lille, Université de Lille 2, France
,
Xavier Marechal   *
1   EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France
,
Steve Lancel
1   EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France
,
Brigitte Decoster
1   EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France
,
Philippe Asseman
2   Soins Intensifs Cardiologiques, Hôpital Cardiologique, CHRU Lille, Université de Lille 2, France
,
Remi Neviere
1   EA 2689, IMPRT –IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, France
› Author AffiliationsFinancial support: This work was supported by grants from EA 2689 Ministère de la Recherche, Université de Lille 2, France.
Further Information

Publication History

Received 11 April 2008

Accepted after major revision 24 August 2008

Publication Date:
22 November 2017 (online)

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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

* These authors contributed equally to this work.


 

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