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首页> 外文期刊>Life sciences >Distinct cardiodynamic and molecular characteristics during early and late stages of sepsis-induced myocardial dysfunction.
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Distinct cardiodynamic and molecular characteristics during early and late stages of sepsis-induced myocardial dysfunction.

机译：脓毒症诱发的心肌功能障碍的早期和晚期，有明显的心脏动力学和分子特征。

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We hypothesized that progressive decline in myocardial performance would correlate with upregulation of markers for apoptotic mechanisms following increased duration of polymicrobial sepsis in the rat. Male Sprague-Dawley rats (350-400 g) were randomized into sham, 1-, 3- and 7-day sepsis groups. Each septic rat received 200 mg/kg cecal inoculum intraperitoneally (i.p). The post-mortem analysis showed a severely inflamed peritoneum with the presence of pus in all septic animals that was directly proportional to the duration of sepsis. We observed 10, 33 and 42% mortality in the 1-, 3- and 7-day sepsis groups, respectively. Septic animals at 3 and 7 days exhibited an increased wet lung/total body weight and heart weight/total body weight. A significant increase in total cardiac troponin I (cTnI) and C Reactive Protein (CRP) and endothelin-1 (ET-1) was also observed with an increased duration of sepsis. Myocardial ET-1 concentration in the 7-day post-sepsis group was significantly elevated compared to the sham and 1-day post-sepsis groups. Sepsis also produced a significant decrease in the mean arterial pressure in the 7-day post-sepsis group and tachycardia in the 1-, 3-, and 7-day post-sepsis groups compared to the sham group. A significant prolongation of the left ventricular isovolumic relaxation rate constant, tau, and left ventricular end-diastolic pressure in the 1-, 3- and 7-day post-sepsis groups compared to the sham group was observed. In addition, a significant decrease in the rates of left ventricular relaxation (-dP/dt) and contraction (+dP/dt) in the 3- and 7-day post-sepsis groups compared to the sham and 1-day post-sepsis group was observed. Sepsis produced a significant upregulation in the expression of myocardial TRADD, cytosolic active caspase-3, the Bax/Bcl(2) ratio, and the mitochondrial release of cytochrome C in the 3- and 7-day post-sepsis groups. We observed a progressive increase in the number of TUNEL positive nuclei, cytosolic caspase-3 activation and co-localization of PARP in the nuclei at 1, 3 and 7 days post-sepsis. These data suggest that the progression of sepsis from 1 day to 3-7 days produce distinct cardiodynamic characteristics with a more profound effect during later stages. The sepsis-induced decline in myocardial performance correlates with the induction of myocardial apoptosis.
机译：我们假设，随着大鼠中微生物败血症持续时间的增加，心肌功能的逐步下降将与凋亡机制标记物的上调相关。将雄性Sprague-Dawley大鼠（350-400 g）随机分为假，第1天，第3天和第7天败血症组。每只脓毒症大鼠腹膜内（i.p）接受200 mg / kg盲肠接种物。验尸分析显示，在所有脓毒症动物中，严重的腹膜发炎和脓液的存在与脓毒症的持续时间成正比。我们分别在1、3和7天的败血症组中观察到10％，33％和42％的死亡率。在第3天和第7天的败血症动物表现出增加的湿肺/总体重和心脏/总体重。随着败血症持续时间的增加，总心肌肌钙蛋白I（cTnI）和C反应蛋白（CRP）和内皮素1（ET-1）的含量也显着增加。与假手术和术后1天相比，脓毒症后7天的心肌ET-1浓度显着升高。与假手术组相比，败血症组在败血症后7天的平均动脉压显着降低，而在脓毒症后1天，3天和7天的心动过速也显着降低。与假手术组相比，在术后第1、3和7天，观察到左室等容松弛常数，tau和左室舒张末期压力显着延长。此外，与假手术和术后第1天相比，在术后第3天和第7天，左室舒张率（-dP / dt）和收缩率（+ dP / dt）显着降低。观察组。脓毒症在脓毒症发作后3天和7天组的心肌TRADD，胞浆活性caspase-3，Bax / Bcl（2）比率以及线粒体细胞色素C的表达中产生了明显的上调。我们观察到在脓毒症发生后1、3和7天，TUNEL阳性细胞核的数量，胞浆caspase-3激活和PARP在细胞核中的共定位在逐渐增加。这些数据表明脓毒症从1天到3-7天的发展过程产生了明显的心脏动力学特征，并在后期阶段产生了更深远的影响。败血症诱导的心肌性能下降与诱导心肌细胞凋亡相关。

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