The synthetic pentasaccharide fondaparinux prevents coronary microvascular injury and myocardial dysfunction in the ischemic heart.
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.
Montaigne
David
D
EA 2689, IMPRT -IFR114, Département de Physiologie, Faculté de Médecine, Université de Lille 2, Lille Cedex 59045 France.
Marechal
Xavier
X
Lancel
Steve
S
Decoster
Brigitte
B
Asseman
Philippe
P
Neviere
Remi
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D000077425:Fondaparinux; D006861:Hydrogen Peroxide / Q000378:metabolism; D036904:Leukocyte Rolling / Q000187:drug effects; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D010766:Phosphorylation; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D011134:Polysaccharides; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077425:Fondaparinux