The Effects of Statins on Cardiac Function and Oxidative Status in Rats with Sepsis

A. M. Samanovic, M. Nikolić, V. Zivkovic, Zeljko Mijailovic, A. Jevtic, M. Andjic, N. Draginic, Maja Savić, S. Bolevich, V. Jakovljevic
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Abstract

Introduction: Sepsis is a life-threatening condition characterized by organ dysfunction evoked by an abnormal host response to an infectious process. Statins, a class of lipid-lowering agents, possess immunomodulatory effects. Having in mind the potential benefit of treatment with statins in sepsis, we aimed to investigate the effects of statins on cardiac function and cardiac oxidative stress (OS) in the experimental sepsis rat model. Methodology: Thirty Wistar Albino rats (males, 8-weeks old, BW were randomly divided into 2 groups: Control group (C,) and animals with induced sepsis (SEPSIS,). After induced sepsis, all animals from the SEPSIS group were randomly divided into 4 subgroups: animals with induced sepsis without treatment (S), animals with induced sepsis treated with a single dose of Atorvastatin, Simvastatin, and Rosuvastatin. After 72h from sepsis induction, all animals were sacrificed and hearts were isolated and perfused according to the Langendorff technique gradually increasing coronary perfusion pressures 40–120 cmH20. In coronary venous effluent were determined the biomarkers of cardiac OS. All data were analyzed by one-way Anova and Kruskal-Wallis tests $(p < 0.05)$. Results: There were no changes in cardiodynamic parameters in septic rats without treatment, as well in those treated with statins, except for coronary flow, where its values were statistically increased in the sepsis group compared to all other groups. Also, sepsis was associated with disturbed cardiac OS and most of the applied therapeutic protocols of statins have mitigated the release of hydrogen peroxide and lipid peroxidation index, while in the case of superoxide anion radical, only atorvastatin at CPP 120 cmH2O had such a positive effect. Conclusion: Given the conditions of the current experiment, we can generally conclude that the rat's hearts in septic conditions were exposed to elevated OS which was not related to its functional changes. Additionally, statin therapy has achieved positive effects in terms of reduced release of molecules that could cause oxidative damage to the rat heart.
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他汀类药物对脓毒症大鼠心功能和氧化状态的影响
简介:败血症是一种危及生命的疾病,其特征是由宿主对感染过程的异常反应引起的器官功能障碍。他汀类药物是一类降脂药物,具有免疫调节作用。考虑到他汀类药物治疗脓毒症的潜在益处,我们旨在研究他汀类药物对实验性脓毒症大鼠心功能和心脏氧化应激(OS)的影响。方法:Wistar Albino大鼠30只,雄性,8周龄,体重,随机分为2组:对照组(C,)和脓毒症(sepsis,)。脓毒症组动物在发生脓毒症后,随机分为4个亚组:未治疗的脓毒症动物(S),单剂量阿托伐他汀、辛伐他汀和瑞舒伐他汀治疗的脓毒症动物。脓毒症诱导72h后,处死所有动物,分离心脏,按照Langendorff技术逐渐升高冠状动脉灌注压40-120 cmH20灌注。在冠状静脉流出液中测定心脏OS的生物标志物。所有数据均采用单因素方差分析和Kruskal-Wallis检验(p < 0.05)。结果:未经治疗的脓毒症大鼠以及接受他汀类药物治疗的大鼠的心脏动力学参数没有变化,除了冠状动脉血流,脓毒症组的冠状动脉血流值与其他各组相比有统计学意义上的增加。此外,脓毒症与心脏OS紊乱有关,大多数他汀类药物的应用治疗方案都减轻了过氧化氢的释放和脂质过氧化指数,而在超氧阴离子自由基的情况下,只有CPP为120 cmH2O的阿托瓦他汀有这样的积极作用。结论:在目前的实验条件下,我们大致可以得出结论,脓毒症大鼠心脏暴露于OS升高,与功能变化无关。此外,他汀类药物治疗在减少可能导致大鼠心脏氧化损伤的分子释放方面取得了积极效果。
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