• Bereketeab Haileselassie, Erik Su, Iraklis Pozios, Diego F Niño, Hongyun Liu, Dai-Yin Lu, Ioannis Ventoulis, William B Fulton, Chhinder P Sodhi, David Hackam, Brian O'Rourke, and Theodore Abraham.
• Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. bhailes3@stanford.edu.
• Intensive Care Med Exp. 2017 Dec 1; 5 (1): 21.

BackgroundRecognition 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.MethodsC57BL/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.ResultsSeptic 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.ConclusionsIn 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.

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