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Muscle squelettique et ischémie-reperfusion expérimentale des membres : mécanismes impliqués dans la protection ou les effets délétères de la cyclosporine et facteurs limitant les conditionnements pharmacologique et ischémique

Abstract : Peripheral arterial disease and many surgical procedures (requiring vascular clamping or tourniquet application) induce severe skeletal muscle ischemia-reperfusion (IR) injuries. As a result, using experimental hind limb ischemia-reperfusion models, our goals were: ° To test a pharmacologic substitute to ischemic postconditioning by using cyclosporine A, that acts on a very downstream step of IR injury cascade by binding to cyclophilin D and inhibiting mitochondrial transition pore opening. We wondered if cyclosporine could alleviate mitochondrial dysfunction and reduce ROS production in skeletal muscles submitted to IR. ° To determine how diabetes and senescence would influence cyclosporine A protective effects. In conclusion, the protective effects of pharmacologic postconditioning with cyclosporine A seem to critically depend on the model under study. A variable and narrow dose-effect relationship is likely and makes it necessary to perform a dose finding study in every pathologic model. Considering the narrow relationships between mitochondrial protection and oxidative stress, combing cyclosporine A postconditioning with antioxidant therapy may restore a more robust protective effect but this hypothesis has to be validated.
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https://tel.archives-ouvertes.fr/tel-00871846
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Submitted on : Thursday, October 10, 2013 - 5:17:09 PM
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Julien Pottecher. Muscle squelettique et ischémie-reperfusion expérimentale des membres : mécanismes impliqués dans la protection ou les effets délétères de la cyclosporine et facteurs limitant les conditionnements pharmacologique et ischémique. Santé publique et épidémiologie. Université de Strasbourg, 2012. Français. ⟨NNT : 2012STRAJ119⟩. ⟨tel-00871846⟩

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