Matkovich Scot J, Al Khiami Belal, Efimov Igor R, Evans Sarah, Vader Justin, Jain Ashwin, Brownstein Bernard H, Hotchkiss Richard S, Mann Douglas L
1Center for Pharmacogenomics, John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO. 2Center for Cardiovascular Research, Cardiovascular Division, John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO. 3Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California, San Diego, CA. 4Department of Biomedical Engineering, George Washington University, Washington, DC. 5Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO.
Crit Care Med. 2017 Mar;45(3):407-414. doi: 10.1097/CCM.0000000000002207.
The mechanism(s) for septic cardiomyopathy in humans is not known. To address this, we measured messenger RNA alterations in hearts from patients who died from systemic sepsis, in comparison to changed messenger RNA expression in nonfailing and failing human hearts.
Identification of genes with altered abundance in septic cardiomyopathy, ischemic heart disease, or dilated cardiomyopathy, in comparison to nonfailing hearts.
ICUs at Barnes-Jewish Hospital, St. Louis, MO.
Twenty sepsis patients, 11 ischemic heart disease, nine dilated cardiomyopathy, and 11 nonfailing donors.
None other than those performed as part of patient care.
Messenger RNA expression levels for 198 mitochondrially localized energy production components, including Krebs cycle and electron transport genes, decreased by 43% ± 5% (mean ± SD). Messenger RNAs for nine genes responsible for sarcomere contraction and excitation-contraction coupling decreased by 43% ± 4% in septic hearts. Surprisingly, the alterations in messenger RNA levels in septic cardiomyopathy were both distinct from and more profound than changes in messenger RNA levels in the hearts of patients with end-stage heart failure.
The expression profile of messenger RNAs in the heart of septic patients reveals striking decreases in expression levels of messenger RNAs that encode proteins involved in cardiac energy production and cardiac contractility and is distinct from that observed in patients with heart failure. Although speculative, the global nature of the decreases in messenger RNA expression for genes involved in cardiac energy production and contractility suggests that these changes may represent a short-term adaptive response of the heart in response to acute change in cardiovascular homeostasis.
人类脓毒症性心肌病的发病机制尚不清楚。为了探究这一问题，我们检测了死于全身性脓毒症患者心脏中的信使核糖核酸（mRNA）变化，并与非衰竭和衰竭的人类心脏中变化的mRNA表达进行比较。
与非衰竭心脏相比，鉴定脓毒症性心肌病、缺血性心脏病或扩张型心肌病中丰度改变的基因。
密苏里州圣路易斯市巴恩斯犹太医院的重症监护病房。
20例脓毒症患者、11例缺血性心脏病患者、9例扩张型心肌病患者和11例非衰竭供体。
除作为患者护理一部分所进行的操作外，无其他干预措施。
198种线粒体定位的能量产生成分的mRNA表达水平，包括三羧酸循环和电子传递基因，下降了43%±5%（平均值±标准差）。脓毒症心脏中负责肌节收缩和兴奋 - 收缩偶联的9个基因的mRNA下降了43%±4%。令人惊讶的是，脓毒症性心肌病中mRNA水平的变化既不同于终末期心力衰竭患者心脏中mRNA水平的变化，且更为显著。
脓毒症患者心脏中mRNA的表达谱显示，编码参与心脏能量产生和心脏收缩力的蛋白质的mRNA表达水平显著下降，且与心力衰竭患者中观察到的情况不同。尽管具有推测性，但参与心脏能量产生和收缩力的基因的mRNA表达下降的全局性表明，这些变化可能代表心脏对心血管内环境稳态急性变化的短期适应性反应。
