Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China.
Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China.
Can J Cardiol. 2019 Jul;35(7):875-883. doi: 10.1016/j.cjca.2019.03.022. Epub 2019 Apr 4.
Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication of sepsis. Mammalian target of rapamycin (mTOR) signalling pathway is significantly associated with SIMD in an animal model; however, there have been no clinical studies of the association in humans.
We enrolled 88 patients with sepsis who were admitted to the intensive care unit (ICU) between April 2017, and April 2018. Biochemical indexes, hemodynamic parameters, and bedside echocardiographic parameters were recorded. Serum levels of mTOR, phosphorylated ribosome S6 protein kinase (PS6K), microtubule-associated protein light chain 3 type II (LC3B), Bcl-2-interacting mediator of cell death (BIM), interleukin 6, interleukin 10, and interferon-γ were examined.
Compared with non-SIMD patients, patients with SIMD had higher ICU and 28-day mortality, PS6K and BIM levels, but lower LC3B levels. Serum PS6K levels in patients with SIMD were significantly negatively and positively correlated with LC3B and BIM, respectively. Multivariate regression analysis revealed that PS6K concentration at admission was an independent predictor of 28-day mortality. Receiver operating characteristic curve analysis indicated that a PS6K concentration cutoff of 42.43 pg/mL at ICU admission could predict the incidence of SIMD with a sensitivity and specificity of 91.7% and 96.2%, whereas a cutoff concentration of 41.17 pg/mL PS6K could predict 28-day mortality with a sensitivity and specificity of 83.3% and 54.3%, respectively.
Patients with sepsis and SIMD had higher ICU and 28-day mortality. Higher serum PS6K concentrations were significantly associated with SIMD incidence and 28-day mortality, suggesting that activation of the mTOR pathway may play a major role in SIMD.
脓毒症诱导的心肌功能障碍（SIMD）是脓毒症的一种危及生命的并发症。在动物模型中，哺乳动物雷帕霉素靶蛋白（mTOR）信号通路与 SIMD 显著相关；然而，在人类中尚未有关于该关联的临床研究。
我们招募了 2017 年 4 月至 2018 年 4 月期间入住重症监护病房（ICU）的 88 例脓毒症患者。记录生化指标、血流动力学参数和床边超声心动图参数。检测 mTOR、磷酸核糖体 S6 激酶（PS6K）、微管相关蛋白轻链 3 型 II（LC3B）、Bcl-2 相互作用的细胞死亡介体（BIM）、白细胞介素 6、白细胞介素 10 和干扰素-γ的血清水平。
与非 SIMD 患者相比，SIMD 患者的 ICU 入住率和 28 天死亡率较高，PS6K 和 BIM 水平较低，LC3B 水平较低。SIMD 患者的血清 PS6K 水平与 LC3B 和 BIM 呈显著负相关和正相关。多变量回归分析显示，入院时 PS6K 浓度是 28 天死亡率的独立预测因子。受试者工作特征曲线分析表明，ICU 入院时 PS6K 浓度 42.43pg/ml 可预测 SIMD 发生率，其敏感性和特异性分别为 91.7%和 96.2%，而 PS6K 浓度 41.17pg/ml 可预测 28 天死亡率，其敏感性和特异性分别为 83.3%和 54.3%。
患有脓毒症和 SIMD 的患者 ICU 入住率和 28 天死亡率较高。较高的血清 PS6K 浓度与 SIMD 发生率和 28 天死亡率显著相关，表明 mTOR 通路的激活可能在 SIMD 中起主要作用。
