Effet protecteur du sulfure d'hydrogène, de la protéine C activée et de la dexamétasone dans la modulation hémodynamique et inflammatoire de l'ischémie/reperfusion

Abstract : Ischemia/reperfusion (I/R) is a very common phenomenon, observed during intestinal artery surgery, shock treatment, as well as in several other diseases. The disruption of tissue perfusion (ischemia) and recovery (reperfusion) induce hemodynamic and metabolic dysfunction. Gut ischemia/reperfusion is often presented as the main source of lactate and the motor of the inflammatory response, such as cardiogenic, hypovolemic and septic shock. In parallel, gut reperfusion produces numerous mediators such as reactive oxygen metabolites, pro-inflammatory cytokines, and high concentrations of nitric oxide. In a model of ischemia/reperfusion induced by hemorrhagic shock, we found that 1) NaHS an injectable form of H2S, limited the decrease in arterial pressure induced by shock and decreased plasmatic lactate, a witness of tissue suffering, 2) this hemodynamic improvement was associated with a fall in myocardial iNOS mRNA expression, a reduction in the concentration of plasmatic NOx and a reduction of aortic and myocardial concentrations of NO and superoxide anion and 3) the inhibition of H2S with DL-propargylglycine worsened hemodynamics and tissue consequences of shock An experimental model of intestinal I/R has been developed, we demonstrated that the administration of APC or Dexa : 1) Improves MAP and vascular reactivity, 2) increased pH and decreased lactate, 3) decreased pro-inflammatory cytokines production and 4) inhibited apoptosis mediators expression. These results are related to a down regulation of iNOS, to a restoration of the AKT/eNOS pathway, and to alpha-adrenoreceptor resensitization. These results open new perspectives in clinical treatment of I/R
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Khodr Issa. Effet protecteur du sulfure d'hydrogène, de la protéine C activée et de la dexamétasone dans la modulation hémodynamique et inflammatoire de l'ischémie/reperfusion. Médecine humaine et pathologie. Université de Lorraine, 2013. Français. ⟨NNT : 2013LORR0059⟩. ⟨tel-01749798⟩

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