• Scot J Matkovich, Belal Al Khiami, Igor R Efimov, Sarah Evans, Justin Vader, Ashwin Jain, Bernard H Brownstein, Richard S Hotchkiss, and Douglas L Mann.
• 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 1; 45 (3): 407-414.

ObjectivesThe 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.DesignIdentification of genes with altered abundance in septic cardiomyopathy, ischemic heart disease, or dilated cardiomyopathy, in comparison to nonfailing hearts.SettingICUs at Barnes-Jewish Hospital, St. Louis, MO.PatientsTwenty sepsis patients, 11 ischemic heart disease, nine dilated cardiomyopathy, and 11 nonfailing donors.InterventionsNone other than those performed as part of patient care.Measurements And Main ResultsMessenger 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.ConclusionsThe 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.

35 keywords...

hide…