Myocardial oxidative stress correlates with left ventricular dysfunction on strain echocardiography in a rodent model of sepsis

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-017-0134-5) contains supplementary material, which is available to authorized users.

Targeting the eCIRP/TREM-1 Interaction with a Small Molecule Inhibitor Improves Cardiac Dysfunction in Neonatal Sepsis

“…[73] Additionally, changes in myocardial strain have been shown to correlate with the upregulation of in ammatory cytokines and mitochondrial dysfunction in the form of an increased in mitochondrial ROS. [72] In our study, eCIRP worsened both longitudinal and radial cardiac strain, providing direct evidence that eCIRP causes cardiac dysfunction in neonatal sepsis.…”

“…[38,71] Myocardial strain can identify sepsis-associated cardiac dysfunction even in the presence of a normal ejection fraction, which can occur with decreased cardiac work and does not accurately re ect cardiac dysfunction. [72] In a meta-analysis of adult patients with sepsis, increased (i.e., less negative) global longitudinal strain values were associated with mortality; this nding was not seen with ejection fraction -the most commonly used parameter to evaluate adult cardiac function in sepsis. [73] Additionally, changes in myocardial strain have been shown to correlate with the upregulation of in ammatory cytokines and mitochondrial dysfunction in the form of an increased in mitochondrial ROS.…”

SAH-Induced Electrophysiological Changes of Ventricular Myocytes and Role of N-acetylcysteine Protection

“…The data from the present and previous studies 33,34 suggest that oxidative stress can be involved in the etiology of cardiovascular pathologies. Result of much work confirms the close relation of the endogenous antioxidant defense mechanisms and ionic current changes.…”

Sepsis‐Induced Cardiomyopathy: Oxidative Implications in the Initiation and Resolution of the Damage

“…LPS-induced myocardial depression (measured as peak tension generated by myocardial contraction) coincides with decreased activity of GPx, the most abundant antioxidant enzyme in myocardium, and decreased levels of GSH, the most important thiol in combating oxidative stress [ 11 ]. Moreover, strain echocardiography identified septic cardiomyopathy which correlates with reduced expression of key mitochondrial ROS scavengers [ 110 ]. In animals, it has been found that both superoxide dismutase and glutathione peroxidase activities, in cardiac mitochondria, decrease (as much as 40% and 70% compared to animals without sepsis) early after sepsis induction and remain at lower levels throughout the first 24 hours after LPS challenge.…”