Dataset Information

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.

SUBMITTER: Haileselassie B

PROVIDER: S-EPMC5389950 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundWe investigated longitudinal right ventricular (RV) function assessed using speckle-tracking strain echocardiography in patient with myocardial infarction (MI), and identified the contributing factors for RV dysfunction.MethodsWe retrospectively studied 71 patients with old MI (the OMI group) and 45 normal subjects (the Control group) who underwent a transthoracic echocardiography. Global and free wall RV peak systolic strains (PSSs) in the longitudinal direction were measured by using speckle-tracking strain echocardiography. Left ventricular (LV) PSSs were measured in the longitudinal, radial and circumferential directions. Cardiac hemodynamics including peak systolic pulmonary artery pressure was also assessed non-invasively. Plasma brain natriuretic peptide (BNP) levels were measured in all patients.ResultsIn the OMI group, 73% of the patients had a normal estimated peak systolic pulmonary artery pressure of less than 35 mmHg. Global and free wall RV PSS were impaired in the OMI group compared with the Control group, and these RV systolic indices were significantly associated with heart rate, logarithmic transformed plasma BNP, greater than 1 year after onset of MI, Doppler-derived estimated pulmonary vascular resistance, LV systolic indices, LV mass index, infarcted segments within a territory of the left circumflex artery and residual total occlusion in the culprit right coronary artery. Multivariable linear regression analysis indicated that reduced longitudinal LV PSS in the 4-chamber view and BNP levels ≥500 pg/ml were independently associated with reduced global and free wall RV PSS. Moreover, when patients were divided into 3 groups according to plasma BNP levels (BNP <100 pg/ml; n = 31, 100 ≤BNP <500 pg/ml; n = 24, and BNP ≥500 pg/ml; n = 16), only patients with BNP ≥500 pg/ml had a strong correlation between RV PSS and longitudinal LV PSS in the 4-chamber view (r = 0.78 for global RV PSS and r = 0.71 for free wall RV PSS, p <0.05).ConclusionLongitudinal RV systolic strain depends significantly on longitudinal LV systolic strain especially in patients with high plasma BNP levels, but not on estimated peak systolic pulmonary artery pressure. These results indicate that process of RV myocardial dysfunction following MI may be governed by neurohormonal activation which causing ventricular remodeling rather than increased RV afterload.

Project description:Aims:More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction. Here, we tested this hypothesis in a swine model chronically exposed to three common comorbidities. Methods and results:DM (induced by streptozotocin), HC (produced by high fat diet), and HT (resulting from renal artery embolization), were produced in 10 female swine, which were followed for 6 months. Eight female healthy swine on normal pig-chow served as controls. The DM + HC + HT group showed hyperglycemia, HC, hypertriglyceridemia, renal dysfunction and HT, which were associated with systemic inflammation. Myocardial superoxide production was markedly increased, due to increased NOX activity and eNOS uncoupling, and associated with reduced NO production, and impaired coronary small artery endothelium-dependent vasodilation. These abnormalities were accompanied by increased myocardial collagen content, reduced capillary/fiber ratio, and elevated passive cardiomyocyte stiffness, resulting in an increased left ventricular end-diastolic stiffness (measured by pressure-volume catheter) and a trend towards a reduced E/A ratio (measured by cardiac MRI), while ejection fraction was maintained. Conclusions:The combination of three common comorbidities leads to systemic inflammation, myocardial oxidative stress, and coronary microvascular dysfunction, which associate with myocardial stiffening and LV diastolic dysfunction with preserved ejection fraction.

Project description:BackgroundLong-term RV pacing leads to ventricular dyssynchrony, in the form of LBBB-like morphology, with subsequent detrimental effects on LV structure and function. Three-dimensional echocardiography allowed early detection of volumetric changes associated with PICMP and provided more accurate assessment of mechanical dyssynchrony. Speckle tracking strain is able to identify LV dysfunction even before any reduction in LVEF. Our aim was to study pacing effects on LV function and hemodynamics using 3D echo and speckle tracking strain.ResultsThis was a prospective study of 175 consecutive patients without structural heart disease (LVEF > 50%) presented for permanent pacing. Full-volume 3D echocardiography done before implantation, 1 week, and 6 months together with GLS. Patients were followed for 6 months to detect incidence of PIVD (defined as reduction in LVEF > 10% but still above 50%) and PICMP (defined as decrease in LVEF by 10% from baseline in absence of other known causes of cardiomyopathy resulting in EF< 50%). PIVD and PICMP predictors and risk factors were analyzed. Only 50 patients met study criteria. Twenty-five (50%) patients developed LV systolic dysfunction; of these, 19 (38%) developed PIVD and 6 (12%) developed PICMP. Pre-implantation GLS was significantly lower in the 6 patients who subsequently developed PICMP, compared to those who developed PIVD and the preserved EF group (mean GLS - 15.50 vs. - 21.0, - 20.0 respectively; p = 0.005, 0.033, respectively). At 1 week, GLS was significantly lower in the 25 patients who subsequently developed PIVD, compared to those who did not (GLS - 13.0 vs. - 18.0, respectively; p = 0.002). A reduction of baseline GLS by 15% or more at 1 week was associated with the development of PIVD and PICMP (p = < 0.001). A wider native QRS complex was associated with PIVD and PICMP (p = 0.008, 0.018, respectively). The other predictors were found non-significant.ConclusionPICMP may be more common than previously reported and it may occur shortly after implantation. Pre-implantation GLS is a sensitive parameter for PICMP. One-week GLS, pre-implantation QRS complex width are early predictors for PICMP and PIVD before any reduction in EF.