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Cardiosensibilisation à l'ischémie-reperfusion induite par l'hypoxie intermittente : rôle de différents agents cardioprotecteurs

Abstract : Obstructive sleep apnea (OSA) is known to be an independent risk factor for coronary heart disease. In the rat, acute and chronic intermittent hypoxia (IH) increases myocardial sensitivity to infarction. Indeed, a 4-h or a 14-day exposure to IH (5% FiO2) aggravates the myocardial lesions induced by an ischemia-reperfusion (I/R) sequence. The aim of this work was to determine whether agents known for their anti-ischemic properties could prevent the deleterious cardiovascular consequences of IH in the rat. Therefore, we have investigated the effects of erythropoietin (EPO), trimetazidine (TMZ), tempol and melatonin on IH-induced myocardial susceptibility to infarction. When administered immediately before or after I/R, exogenous EPO dose-dependently prevented the acute IH-induced increase in infarct size in the isolated rat heart. Tempol and melatonin were also able to prevent the deleterious cardiovascular effects of IH through their antioxidant properties. Indeed, when administered daily during a 14-day IH exposure, these treatments significantly abolished both the increase in infarct size and in mean arterial blood pressure. Moreover, tempol prevented myocardial superoxide anion generation and expression of the NADPH oxidase sub-unit p47-phox, suggesting a role for oxidative stress in the deleterious cardiac effects of IH in the rat. However, TMZ administration throughout IH exposure was without significant effects suggesting that the anti-ischemic actions of this agent are not sufficient to counteract the IH-induced myocardial susceptibility to infarction. Additional studies are now required to explore the mechanisms involved in these deleterious effects and in particular the exact contribution of oxidative stress. This will enable the development of clinical perspectives and of novel therapeutic strategies for OSA syndrome.
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Contributor : Amandine Ramond <>
Submitted on : Tuesday, March 8, 2011 - 10:05:25 AM
Last modification on : Friday, November 6, 2020 - 3:44:02 AM
Long-term archiving on: : Thursday, June 9, 2011 - 2:30:05 AM

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Amandine Ramond. Cardiosensibilisation à l'ischémie-reperfusion induite par l'hypoxie intermittente : rôle de différents agents cardioprotecteurs. Physiologie [q-bio.TO]. Université de Grenoble, 2010. Français. ⟨tel-00574469⟩

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