Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice

The role of NADPH oxidase subunit, gp91phox (NOX2) in development of oxidative stress and cardiac dysfunction due to iron (Fe)-overload was assessed. Control (C57BL/6J) and gp91phox knockout (KO) mice were treated for up to 8 weeks with Fe (2.5 mg/g/wk, i.p.) or Na-dextran; echocardiography, plasma 8-isoprostane (lipid peroxidation marker), cardiac Fe accumulation (Perl’s staining), and CD11b+ (WBCs) infiltrates were assessed. Fe caused no adverse effects on cardiac function at 3 weeks. At 6 weeks, significant declines in left ventricular (LV) ejection fraction (14.6% lower), and fractional shortening (19.6% lower) occurred in the Fe-treated control, but not in KO. Prolonging Fe treatment (8 weeks) maintained the depressed LV systolic function with a trend towards diastolic dysfunction (15.2% lower mitral valve E/A ratio) in controls but produced no impact on the KO. Fe-treatment (8 weeks) caused comparable cardiac Fe accumulation in both strains, but a 3.3-fold elevated plasma 8-isoprostane, and heightened CD11b+ staining in controls. In KO mice, lipid peroxidation and CD11b+ infiltration were 50% and 68% lower, respectively. Thus, gp91phox KO mice were significantly protected against oxidative stress, and systolic and diastolic dysfunction, supporting an important role of NOX2-mediated oxidative stress in causing cardiac dysfunction during Fe overload.

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Tachycardia-induced myocardial ischemia and diastolic dysfunction potentiate secretion of ANP, not BNP, in hypertrophic cardiomyopathy

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00110.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. H1064-H1070 ◽

Cited By ~ 2

Author(s):

Shinsuke Kido ◽

Naoyuki Hasebe ◽

Yoshinao Ishii ◽

Kenjiro Kikuchi

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Myocardial Ischemia ◽

Diastolic Dysfunction ◽

Diastolic Pressure ◽

Systolic Function ◽

Left Ventricular ◽

Atrial Pacing ◽

Catheter Tip ◽

Lv Systolic Function ◽

Lv Diastolic Dysfunction

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery ( n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls ( n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 ± 101 to 1,268 ± 334 pg/ml ( P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM ( P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER ( r = −0.57, P < 0.01) and tau ( r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.

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Echocardiographic Assessment of Left Ventricular Geometric Patterns in Hypertensive Patients in Nigeria

Clinical Medicine Insights Cardiology ◽

10.4137/cmc.s12727 ◽

2013 ◽

Vol 7 ◽

pp. CMC.S12727 ◽

Cited By ~ 1

Author(s):

Rasaaq A. Adebayo ◽

Olaniyi J. Bamikole ◽

Michael O. Balogun ◽

Anthony O. Akintomide ◽

Victor O. Adeyeye ◽

...

Keyword(s):

Diastolic Dysfunction ◽

Systolic Function ◽

Left Ventricular ◽

Geometric Pattern ◽

Color Flow ◽

Hypertensive Patients ◽

Geometric Patterns ◽

Concentric Hypertrophy ◽

Eccentric Hypertrophy ◽

Lv Systolic Function

Left ventricular (LV) hypertrophy is an important predictor of morbidity and mortality in hypertensive patients, and its geometric pattern is a useful determinant of severity and prognosis of heart disease. Studies on LV geometric pattern involving large number of Nigerian hypertensive patients are limited. We examined the LV geometric pattern in hypertensive patients seen in our echocardiographic laboratory. A two-dimensional, pulsed, continuous and color flow Doppler echocardiographic evaluation of 1020 consecutive hypertensive patients aged between 18 and 91 years was conducted over an 8-year period. LV geometric patterns were determined using the relationship between the relative wall thickness and LV mass index. Four patterns of LV geometry were found: 237 (23.2%) patients had concentric hypertrophy, 109 (10.7%) had eccentric hypertrophy, 488 (47.8%) had concentric remodeling, and 186 (18.2%) had normal geometry. Patients with concentric hypertrophy were significantly older in age, and had significantly higher systolic blood pressure (BP), diastolic BP, and pulse pressure than those with normal geometry. Systolic function index in patients with eccentric hypertrophy was significantly lower than in other geometric patterns. Doppler echocardiographic parameters showed some diastolic dysfunction in hypertensive patients with abnormal LV geometry. Concentric remodeling was the most common LV geometric pattern observed in our hypertensive patients, followed by concentric hypertrophy and eccentric hypertrophy. Patients with concentric hypertrophy were older than those with other geometric patterns. LV systolic function was significantly lower in patients with eccentric hypertrophy and some degree of diastolic dysfunction were present in patients with abnormal LV geometry.

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Abstract 2292: Torsional Deformation Delay: a Novel Echocardiographic Index of Left Ventricular Peak Rotation Sequence Between Basal and Apical Level.

Circulation ◽

10.1161/circ.116.suppl_16.ii_500-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Lukasz Chrzanowski ◽

Barbara Uznanska ◽

Michal Plewka ◽

Piotr Lipiec ◽

Jaroslaw Drozdz ◽

...

Keyword(s):

Systolic Function ◽

Temporal Distribution ◽

Left Ventricular ◽

Torsional Deformation ◽

Lv Mass ◽

Echocardiographic Parameters ◽

The Difference ◽

Lv Systolic Function ◽

Rotation Sequence

Purpose: left ventricular (LV) torsion (TOR) results from oppositely directed rotation (ROT) at the basal (BAS) and apical (AP) level. Speckle Tracking Echocardiography (STE) allows TOR assessment, but little is known of LV ROT temporal distribution. The aim was to evaluate the sequence of BAS and AP level ROT and to identify associated echocardiographic parameters. Methods: 48 patients (PTS) were studied (mean age 54±13 years, 23 men). LV systolic function was normal in 23 PTS (LVEF 60% or more), and various degrees of dysfunction were present in 25 PTS (mean LVEF 40±10%). Digital short axis loops at BAS and AP level were analyzed using STE algorithm to measure ROT in degrees (°). After adjustment for heart rate, Torsional Deformation Delay (TDD) was calculated as the difference between the time from the onset of QRS complex to the peak average systolic ROT at BAS and AP level (figure ). Results: mean TOR, BAS ROT and AP ROT was 14.3±7.3°, −6.8±4.7° and 7.5±6.1° respectively. Mean TDD was 19±107 ms (range from −285 to 248 ms); negative TDD indicated shorter time to BAS peak ROT. No difference of mean TDD was found between PTS with normal and decreased LVEF. TDD outside the range of −28 ms to 28 ms, derived by ROC analysis, was shown to have 96% specificity in detecting PTS with LVEF <60%. It was also associated with higher LV mass index as compared to TDD ranging from −28 to 28 ms (130 g/m2 vs 100 g/m2, p=0.025). Conclusions: a novel TDD index allows evaluation of LV ROT temporal distribution between BAS and AP level. TDD values outside the range of −28 ms to 28 ms are associated with decreased LVEF and presence of LV hypertrophy. Further studies are required to assess the role of TDD in cardiac imaging.

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Valve Replacement for Aortic Stenosis in Patients With Poor Left Ventricular Function

Circulation ◽

10.1161/circ.100.suppl_2.ii-1 ◽

1999 ◽

Vol 100 (suppl_2) ◽

Author(s):

Julian Collinson ◽

Michael Henein ◽

Marcus Flather ◽

John R. Pepper ◽

Derek G. Gibson

Keyword(s):

Aortic Stenosis ◽

Systolic Function ◽

Left Ventricular ◽

Lv Function ◽

Valve Prosthesis ◽

Transthoracic Doppler Echocardiography ◽

Early Improvement ◽

Lv Dysfunction ◽

Lv Systolic Function ◽

Fractional Shortening

Background —Long-standing aortic stenosis causes significant left ventricular (LV) dysfunction, which may progress irreversibly. In many cases, LV function can be salvaged by aortic valve surgery, although debate exists regarding the best valve prosthesis to use. Methods and Results —We studied 33 patients retrospectively who had significant aortic stenosis and impaired LV systolic function, as assessed by transthoracic Doppler echocardiography. Patients were assessed preoperatively and before discharge from the hospital. A total of 20 patients received a stentless (homograft or Toronto) valve, and 13, a stented valve. No patient had significant aortic regurgitation or other valvular disease. Preoperatively, fractional shortening was 18.8±5.5% in the stentless group and 18.6±3.8% in the stented group. Postoperatively, it was 25.6±6.9% ( P <0.001 compared with baseline) and 17.0±2.8%, respectively ( P <0.001 compared with stentless group). Fractional shortening improved because of a reduction in LV end-systolic and end-diastolic dimensions in the stentless group. Systolic long axis function at the LV free wall also recovered, with an increase in systolic excursion and both peak shortening and lengthening rates. No change was noted in mitral valve Doppler patterns. Conclusions —Patients who received a stentless valve demonstrated a significantly greater early improvement in LV systolic function compared with those who received a stented valve.

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Genetic inhibition of calcineurin induces diastolic dysfunction in mice with chronic pressure overload

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00449.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. H1814-H1819 ◽

Cited By ~ 14

Author(s):

Ricardo J. Gelpi ◽

Shumin Gao ◽

Peiyong Zhai ◽

Lin Yan ◽

Chull Hong ◽

...

Keyword(s):

Diastolic Dysfunction ◽

Diastolic Function ◽

Systolic Function ◽

Pressure Overload ◽

Left Ventricular ◽

Aortic Banding ◽

Lv Systolic Function ◽

Calcineurin Inhibition ◽

Lv Diastolic Function ◽

Isovolumic Relaxation

Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase that induces myocardial growth in response to several physiological and pathological stimuli. Calcineurin inhibition, induced either via cyclosporine or genetically, can decrease myocardial hypertrophy secondary to pressure overload without affecting left ventricular (LV) systolic function. Since hypertrophy can also affect LV diastolic function, the goal of this study was to examine the effects of chronic pressure overload (2 wk aortic banding) in transgenic (Tg) mice overexpressing Zaki-4β (TgZ), a specific endogenous inhibitor of calcineurin, on LV diastolic function. As expected, in the TgZ mice with calcineurin inhibitor overexpression, aortic banding reduced the degree of LV hypertrophy, as assessed by LV weight-to-body weight ratio (3.5 ± 0.1) compared with that in non-Tg mice (4.6 ± 0.2). LV systolic function remained compensated in both groups with pressure overload. However, the LV end-diastolic stress-to-LV end-diastolic dimension ratio, an index of diastolic stiffness and LV pressure half-time and isovolumic relaxation time, two indexes of isovolumic relaxation, increased significantly more in TgZ mice with aortic banding. Protein levels of phosphorylated phospholamban (PS16), sarco(endo)plasmic reticulum Ca2+-ATPase 2a, phosphorylated ryanodine receptor, and the Na+/Ca2+ exchanger were also reduced significantly ( P < 0.05) in the banded TgZ mice. As expected, genetic calcineurin inhibition inhibited the development of LV hypertrophy with chronic pressure overload but also induced LV diastolic dysfunction, as reflected by both impaired isovolumic relaxation and increased myocardial stiffness. Thus genetic calcineurin inhibition reveals a new mechanism regulating LV diastolic function.

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New Echocardiographic Findings Correlate with Intramyocardial Inflammation in Endomyocardial Biopsies of Patients with Acute Myocarditis and Inflammatory Cardiomyopathy

Mediators of Inflammation ◽

10.1155/2013/875420 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 33

Author(s):

Felicitas Escher ◽

Mario Kasner ◽

Uwe Kühl ◽

Johannes Heymer ◽

Ursula Wilkenshoff ◽

...

Keyword(s):

Speckle Tracking ◽

Speckle Tracking Echocardiography ◽

Systolic Function ◽

Acute Myocarditis ◽

Left Ventricular ◽

Inflammatory Cardiomyopathy ◽

Lv Systolic Function ◽

Lymphocytic Infiltrates ◽

Fractional Shortening

Background. The diagnosis of acute myocarditis (AMC) and inflammatory cardiomyopathy (DCMi) can be difficult. Speckle tracking echocardiography with accurate assessments of regional contractility could have an outstanding importance for the diagnosis.Methods and Results.N=25patients with clinically diagnosed AMC who underwent endomyocardial biopsies (EMBs) were studied prospectively. Speckle tracking imaging was examined at the beginning and during a mean follow-up period of 6.2 months. In the acute phase patients had markedly decreased left ventricular (LV) systolic function (mean LV ejection fraction (LVEF)40.4±10.3%). At follow-up inn=8patients, inflammation persists, correlating with a significantly reduced fractional shortening (FS,21.5±6.0%) in contrast to those without inflammation in EMB (FS32.1±7.1%,P<0.05). All AMC patients showed a reduction in global systolic longitudinal strain (LS,−8.36±−3.47%) and strain rate (LSR,0.53±0.29 1/s). At follow-up, LS and LRS were significantly lower in patients with inflammation, in contrast to patients without inflammation (−9.4±1.4versus−16.8±2.0%,P<0.0001;0.78±0.4versus1.3±0.3 1/s). LSR and LS correlate significantly with lymphocytic infiltrates (for CD3r=0.7,P<0.0001, and LFA-1r=0.8,P<0.0001).Conclusion. Speckle tracking echocardiography is a useful adjunctive assisting tool for evaluation over the course of intramyocardial inflammation in patients with AMC and DCMi.

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Neutrophil to Lymphocyte Ratio is Increased and Associated with Left Ventricular Diastolic Function in Newly Diagnosed Essential Hypertension Children.

10.21203/rs.3.rs-27242/v1 ◽

2020 ◽

Author(s):

Miao Hou ◽

Lei Cao ◽

Yueyue Ding ◽

Ye Chen ◽

Bo Wang ◽

...

Keyword(s):

Essential Hypertension ◽

Diastolic Dysfunction ◽

Diastolic Function ◽

Systolic Function ◽

Left Ventricular ◽

Neutrophil To Lymphocyte Ratio ◽

Healthy Children ◽

Newly Diagnosed ◽

Lymphocyte Ratio ◽

Lv Systolic Function

Abstract Aim Hypertension is associated with cardiac structural and functional changes, including left ventricular hypertrophy (LVH), LV systolic dysfunction, and diastolic dysfunction. Neutrophil to lymphocyte ratio (NLR) is a novel inflammatory biomarker associated with cardiovascular diseases. The current study aimed to evaluate NLR in children with newly diagnosed essential hypertension and its relationship between blood pressure and cardiac changes. Methods and subjects 44 children with newly diagnosed essential hypertension and 43 healthy children were included. Clinical characteristics, blood cell counts and biochemical parameters were collected. LVH was assessed by calculation of LV mass index (LVMI), and LV systolic function was evaluated by measuring LV ejection fraction and fractional shortening. LV diastolic function was primarily assessed with E/E’ ratio by doppler and echocardiography. Results The hypertension children had significantly higher LVMI and E/E’ ratio compared to the controls, whereas there was no difference in LV systolic function between two groups. The NLR was significantly higher in the hypertension group than the control group. Moreover, NLR and it was positively correlated with SBP and DBP levels in the hypertension group. Additionally, a significantly positive correlation between NLR and E/E’ ratio was found in the hypertension group. However, NLR was not related to LVH and LV systolic function indicators in hypertension children.Conclusion The higher NLR may be a potential indicator of increased risk for the development of hypertension in children. Moreover, NLR may help to assess the presence of LV diastolic dysfunction in hypertension children.

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P897 The role of oxidative stress and inflammation for stress induced left ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease patients

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.535 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

Z Cherneva ◽

V L Lozanov ◽

P S Sugareva ◽

R C H Cherneva

Keyword(s):

Oxidative Stress ◽

Diastolic Dysfunction ◽

Left Ventricular Diastolic Dysfunction ◽

Urine Concentration ◽

Left Ventricular ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Ventricular Diastolic Dysfunction ◽

Severe Copd

Abstract Background Oxidative stress and inflammation have been implicated in the pathogenesis of diastolic dysfunction (DD) and are both present in chronic obstructive pulmonary disease (COPD). Purpose To evaluate the role of oxidative stress markers (8-isoprostane) and inflammation (prostaglandin E2, resistin) in the pathogenesis of stress induced left ventricular diastolic dysfunction (LVDD) in non-severe COPD. Materials and methods 104 patients with non-severe COPD (FEV1 > 50%) and preserved left ventricular ejection fraction >50% underwent incremental cardio-pulmonary exercise testing (CPET). Echocardiography was performed before CPET and 1-2 minutes after peak exercise. Peak E/e’ ratio >15 was a marker for stress LVDD. Urine concentration of 8-isoprostanes was assumed as surrogate marker for oxidative stress; urine concentration of prostaglandine-E2 and plasma resistin levels as inflammatory markers. Mass spectrometry was applied for 8-isoprostane and prostglandine E2 (Cayman. Chemical) measurement. Values were normalised to urine creatinine (µmol/l/cre). ELISA was applied for resistin measurement (Raybio_Human) (ng/ml). Results Patients were divided into two groups: subjects with stress LVDD (67) and subjects without stress LVDD (37). 8-isoprostane levels were higher in subjects with LVDD vs those without LVDD (32.9 vs 29.67µmol/l/cre; p< 0.05). The same is observed regarding resistin plasma levels (22.51 vs 15.68ng/ml). Urine concentrations of prostaglandin E2 did not differ between the two groups (50.76 vs 51.07 µmol/l/cre) Conclusions In non-severe COPD patients the levels of oxidative stress (8-isoprostanes) and inflammation (resistin) seem to be associated with stress induced left ventricular diastolic dysfunction.

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Link between diabetes and diastolic dysfunction and the diagnostic role of echocardiography

Orvosi Hetilap ◽

10.1556/oh.2009.28738 ◽

2009 ◽

Vol 150 (45) ◽

pp. 2060-2067 ◽

Cited By ~ 1

Author(s):

András Nagy ◽

Zsuzsanna Cserép

Keyword(s):

Heart Failure ◽

Diastolic Dysfunction ◽

Systolic Function ◽

Diastolic Heart Failure ◽

Systolic Dysfunction ◽

Mitral Annulus ◽

Left Ventricular ◽

Diabetic Patients ◽

Doppler Study

Diabetes mellitus, a disease that has been reaching epidemic proportions, is an important risk factor to the development of cardiovascular complication. The left ventricular diastolic dysfunction represents the earliest pre-clinical manifestation of diabetic cardiomyopathy, preceding systolic dysfunction and being able to evolve to symptomatic heart failure. In early stages, these changes appear reversible with tight metabolic control, but as pathologic processes become organized, the changes are irreversible and contribute to an excess risk of heart failure among diabetic patients. Doppler echocardiography provides reliable data in the stages of diastolic function, as well as for systolic function. Combination of pulsed tissue Doppler study of mitral annulus with transmitral inflow may be clinically valuable for obtaining information about left ventricular filling pressure and unmasking Doppler inflow pseudonormal pattern, a hinge point for the progression toward advanced heart failure. Subsequently we give an overview about diabetes and its complications, their clinical relevance and the role of echocardiography in detection of diastolic heart failure in diabetes.

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Abstract 311: Early Losartan Treatment Prevents the Developmental Programming of Cardiac Dysfunction Caused by Neonatal High Oxygen Exposure in Rats

Hypertension ◽

10.1161/hyp.64.suppl_1.311 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Mariane Bertagnolli ◽

Sarah Béland-Bonenfant ◽

Anne Dios ◽

Daniela R Dartora ◽

Marie-Amélie Lukaszewski ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Dysfunction ◽

Systolic Function ◽

Developmental Programming ◽

Term Treatment ◽

Short Term ◽

Short Term Treatment ◽

High O2 ◽

Cardiac Alterations

Neonatal oxidative stress is a major postnatal deleterious factor predisposing preterm born infants to classical complications of prematurity (retinopathy, bronchopulmonary dysplasia) which are characterized by impaired vascular development. Our group has previously shown that rats transiently exposed to high O2 as newborns (mimicking human preterms oxidative stress conditions) develop high blood pressure (BP), cardiac remodeling and dysfunction later in life, in part mediated by the renin angiotensin system (RAS). Cardiac RAS activation is characterized by AT1/AT2 receptors imbalance, with increased AT1R at adult age. In order to study the role of RAS at early stages of the developmental programming of cardiac dysfunction caused by high O2 exposure, we assessed whether an early and short-term treatment with AT1R blocker Losartan, prevents cardiac alterations at young male 4 wks-old rats (prior to the elevation of BP in this model). Sprague-Dawley newborns rats were kept with their mother in 80% O2 (O2 group, n=9) or room air (Ctrl, n=9) from days 3-10 of life (P3-P10). Losartan (LOS, n=10, 20 mg/Kg) or water was administered by gavage in O2 rats from P8-P10 (last 2 days of O2 to avoid impact on nephrogenesis). At 4 wks, echocardiography reveals that O2 rats have decreased fraction of shortening compared to Ctrl (FS: 37±2 vs 42±2 %), suggesting impaired systolic function in O2. Cardiac hypertrophy evaluated by heart/body weight and cardiomyocyte surface area (CSA) is also increased in O2 vs Ctrl (141±13 vs 118±4 μm2). LOS treatment prevented the impairment of systolic function in O2 by ameliorating FS (43±2 %) and reducing CSA (121±11 μm2). LOS treatment also modulated RAS genes expression (RT-PCR): LOS restored AT1/AT2 balance in O2 hearts by decreasing AT1b subunit (0.8±0.2 O2 vs 1.3±0.3 O2+LOS vs 0.9±0.2 Ctrl) as well as increasing ACE2 (1.5±0.4 O2 vs 0.8±0.1 O2+LOS vs 1.1±0.4 Ctrl) expressions. In conclusion, a short-term treatment with LOS during neonatal O2 exposure prevents the impairment of cardiac systolic function and hypertrophy at young age. This data reinforces the key role of RAS in the developmental programming of cardiac dysfunction and reveals LOS as an effective strategy to prevent early cardiac alterations caused by neonatal high O2 exposure.

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