Effet de la combinaison de l'hypertension et de l'infarctus du myocarde sur la physiopathologie du choc septique : mise au point d'un modèle animal expérimental mimant le phénotype des patients septiques

Abstract : Septic shock is considered as the most common cause of death among patients admitted in medical intensive care units. Mortality remains very high (50%) despite advances in physiopathological knowledge of this disease. In fact, most experimental studies are often conducted on young and healthy animals, whereas it is well established that the incidence and mortality rates dramatically increase with age. The goal of this study was to evaluate the effect of the combination of two diseases (hypertension and myocardial infarction) in a septic rat model, on cardiovascular function, cell survival and the inflammatory response. Therefore, we used normotensive Wistar-Kyoto rats (WKY) and Spontaneously Hypertensive Rats (SHR) in which myocardial infarction was induced by left coronary descending artery ligation, followed or not by cecal ligation and perforation-induced sepsis. Our results showed that the polypathological SHR rats in which a myocardial infarction and sepsis were induced, exhibited a significant decrease in cardiac and hemodynamic parameters compared to WKY rats that have sepsis (CLP) only. Indeed, cardiac output, mean arterial pressure and ejection fraction were reduced by 70%, 60% and 67% respectively in the polypathological SHR rats versus the WKY rats with sepsis. We observed also that the vascular hyporeactivity in the polypathological SHR rats was higher than for the WKY CLP rats. A mesure of gene expression level of alpha1 adrenergic receptor shows a relatively low expression level in the rats from SHR IDM CLP rats compared to WKY CLP that could explain the observed vasodilation. The protein level of caspase3 and 8, Pp38 and proteins involved in apoptosis, is upregulated in SHR IDM CLP rats compared to WKY CLP rats. However, the polypathological SHR rats show a significant decrease in the expression of eNOS and Akt protein compared to WKY CLP rats. The combination of hypertension with myocardial infarct is associated with higher sensitivity of the rats to sepsis. The polypathological SHR rats developed a severe heart failure compared to WKY rats having sepsis only. Our animal model, the polypathological SHR rats is very close to observed clinical situations in intensive care units. This model could serve as a good candidate for pre-clinical studies.
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Theses
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http://docnum.univ-lorraine.fr/ulprive/DDOC_T_2016_0176_AL_KATTANI.pdf
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Submitted on : Thursday, March 29, 2018 - 1:45:14 PM
Last modification on : Friday, March 30, 2018 - 1:32:27 AM

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Narimane Al Kattani. Effet de la combinaison de l'hypertension et de l'infarctus du myocarde sur la physiopathologie du choc septique : mise au point d'un modèle animal expérimental mimant le phénotype des patients septiques. Médecine humaine et pathologie. Université de Lorraine, 2016. Français. ⟨NNT : 2016LORR0176⟩. ⟨tel-01752406⟩

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