title: Myocardial oxidative stress correlates with left ventricular dysfunction on strain echocardiography in a rodent model of sepsis.
abstract: BACKGROUND
  Recognition of cardiomyopathy in sepsis can be challenging due to the limitations of conventional measures such as ejection fraction (EF) and fractional shortening (FS) in the context of variable preload and afterload conditions. This study correlates myocardial function using strain echocardiography (SE) with cardiomyocyte oxidative stress in a murine model of sepsis.
  
  
  METHODS
  C57BL/6J mice were randomized into control (n = 10), sham (n = 25), and a cecal ligation and puncture (CLP) (n = 33) model of sepsis. Echocardiography was performed pre-, 12, 24, and 48 h post-injury. Cardiac pro-inflammatory cytokines and mitochondrial redox scavenger expression were evaluated in a subset of each arm. To evaluate the influence of redox scavenger upregulation on oxidative injury and cardiac function, CLP was performed on mitochondrial catalase-upregulated C57BL/6J MCAT+/+mice (n = 12) and wild-type (WT) animals for comparison.
  
  
  RESULTS
  Septic C57BL/6J mice exhibited depressed longitudinal strain (LS) when compared to sham and control at 24 h (p < 0.01) and 48 h (p = 0.04) post-CLP despite having a preserved EF. Furthermore, there was a significant association between increased odds of mortality and depressed LS (OR = 1.23, p = 0.04). Septic C57BL/6J mice concomitantly demonstrated increased expression of cardiomyocyte pro-inflammatory cytokines and decreased expression of redox scavengers at 24 and 48 h. When comparing C57Bl/6 MCAT+/+mice and C57BL/6J WT mice, a significant decrease in LS was identified in the WT mice at 24 h (MCAT = -23 ± 5% vs. WT = -15 ± 4% p < 0.01) and 48 h (MCAT = -23 ± 7% vs. WT = -15 ± 4.3% p = 0.04) post-CLP which correlated with significant increase in the level of cardiac oxidative stress following CLP.
  
  
  CONCLUSIONS
  In this sepsis model, SE identified cardiomyopathy despite normal EF. SE depression temporally coincides with upregulation of inflammatory cytokines and decreases expression of key mitochondrial ROS scavengers. Upregulation of redox scavenger (CAT) abrogates oxidative stress and cardiac dysfunction in this sepsis model.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. bhailes3@stanford.edu.|Department of Pediatrics, Division of Critical Care, Stanford University School of Medicine, 770 Welch Road, Suite 435, Palo Alto, CA, 94304-5731, USA. bhailes3@stanford.edu.
authors.forename: Bereketeab
authors.identifier: http://orcid.org/0000-0002-0120-3366
authors.initials: B
authors.lastname: Haileselassie
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Su
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Iraklis
authors.initials: I
authors.lastname: Pozios
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Niño
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Dai-Yin
authors.initials: DY
authors.lastname: Lu
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Ventoulis
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Fulton
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Chhinder P
authors.initials: CP
authors.lastname: Sodhi
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hackam
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: O'Rourke
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Theodore
authors.initials: T
authors.lastname: Abraham
keywords: Sepsis; Sepsis-induced myocardial dysfunction; Shock; Ultrasound