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
