scholarly journals Effects of atrial fibrillation on ventricular remodeling in the human heart

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Pabel ◽  
M Knierim ◽  
T Stehle ◽  
F Alebrand ◽  
M Paulus ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Atrial Fibrillation ◽  
Sarcoplasmic Reticulum ◽  
Clinical Data ◽  
Ventricular Remodeling ◽  
Negative Impact ◽  
Left Ventricular ◽  
Public Institution ◽  
Transient Kinetics ◽  
Ec Coupling

Abstract   Atrial fibrillation (AF) is often found in patients with heart failure (HF). Clinical data indicated that the arrhythmic component of AF alone could contribute to left-ventricular (LV) dysfunction. However, the effects of non-tachycardic AF with arrhythmic excitation of the human LV, are unknown. We investigated human LV myocardium from patients with sinus rhythm (SR) or normofrequent AF (mean EF>50%, matched clinical data, derived from septal resections during AVR). In histological analysis we detected no difference between SR (n=17 patients) and AF patients (n=18) regarding the amount and distribution of fibrosis. We isolated human LV cardiomyocytes (CM) and studied cellular Ca-handling (Fura-2). Systolic Ca-transient amplitude of LV CM was reduced in patients suffering from AF (n=8 AF patients vs. 11 SR), while diastolic Ca-levels and Ca-transient kinetics were not significantly changed. These results were confirmed in LV CM from non-failing donors (NF) with AF (n=4 AF patients vs. 8 SR). For the standardized investigation of a normofrequent arrhythmia, we simulated AF in vitro by using arrhythmic (60 bpm, 40% beat-to-beat variability) or rhythmic (60 bpm) field stimulation. Human LV CM from NF SR patients (n=8) showed an impaired Ca-transient amplitude after 24h arrhythmic culture pacing without changes in diastolic Ca and Ca-transient kinetics. For studying a model suitable for more standardized chronic pacing, we utilized human iPSC cardiomyocytes (iPSC-CM) from healthy donors (n=6). After 7 days, arrhythmically paced iPSC-CM exhibited a reduced systolic Ca-transient amplitude, a trend towards a prolonged Ca-elimination time and a reduced sarcoplasmic reticulum Ca-load. Confocal line-scans of arrhythmically paced cells (Fluo-4 AM) showed an increased diastolic Ca-leak from the sarcoplasmic reticulum, possibly underlying the reduced Ca-load. Coupled with the Ca changes, cytosolic Na was elevated after arrhythmia. We found an increased late INa, which could explain the detrimentally altered Ca/Na-interplay. Accordingly, Patch-clamp experiments revealed a prolonged action potential duration after arrhythmia. We further elucidated the underlying mechanisms of this electrophysiological remodeling by showing that oxidative stress (H2O2, LPO) is increased in the LV of patients suffering from AF (n=6 AF patients vs. 6 SR), which was associated with an enhanced NOX2/-4 activity. Consecutively, Ca2+/calmodulin-dependent protein kinase IIδ (CaMKII) was found to be more oxidized (CaMKII-Met281/282) in the LV of AF patients (n=7 AF patients vs. 7 SR) leading to an increased CaMKII activity, which adversely regulated EC-coupling protein phosphorylation including RyR2 hyperphosphorylation. Normofrequent arrhythmia/AF impairs human ventricular EC-coupling via increased oxidative stress and enhanced CaMKII. Thus, this translational study provides the first mechanistic characterization and the potential negative impact of isolated AF on the human LV. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Else Kröner-Fresenius-Stiftung (EKFS) and Deutsche Gesellschaft für Innere Medizin

The Pattern of Ventricular Remodeling Influences the Level of Oxidative Stress in Heart Failure Patients

2017 ◽  
Vol 68 (7) ◽  
pp. 1506-1511
Author(s):  
Cerasela Mihaela Goidescu ◽  
Anca Daniela Farcas ◽  
Florin Petru Anton ◽  
Luminita Animarie Vida Simiti
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Clinical Laboratory ◽  
Left Ventricular ◽  
Control Group ◽  
Reactive Protein ◽  
Lv Mass ◽  
Few Data

Oxidative stress (OS) is increased in chronic diseases, including cardiovascular (CV), but there are few data on its effects on the heart and vessels. The isoprostanes (IsoP) are bioactive compounds, with 8-iso-PGF25a being the most representative in vivo marker of OS. They correlate with the severity of heart failure (HF), but because data regarding OS levels in different types of HF are scarce, our study was aimed to evaluate it by assessing the urinary levels of 8-iso-PGF2aand its correlations with various biomarkers and parameters. Our prospective study included 53 consecutive patients with HF secondary to ischemic heart disease or dilative cardiomyopathy, divided according to the type of HF (acute, chronic decompensated or chronic compensated HF). The control group included 13 hypertensive patients, effectively treated. They underwent clinical, laboratory - serum NT-proBNP, creatinine, uric acid, lipids, C reactive protein (CRP) and urinary 8-iso-PGF2a and echocardiographic assessment. HF patients, regardless the type of HF, had higher 8-iso-PGF2a than controls (267.32pg/�mol vs. 19.82pg/�mol, p[0.001). The IsoP level was directly correlated with ejection fraction (EF) (r=-0.31, p=0.01) and NT-proBNP level (r=0.29, p=0.019). The relative wall thickness (RWT) was negatively correlated with IsoP (r=-0.55, p[0.001). Also 8-iso-PGF25a was higher by 213.59pg/�mol in the eccentric left ventricular (LV) hypertrophy subgroup comparing with the concentric subgroup (p=0.014), and the subgroups with severe mitral regurgitation (MR) and moderate/severe pulmonary hypertension (PAH) had the highest 8-iso-PGF2a levels. Male sex, severe MR, moderate/severe PAH, high LV mass and low RWT values were predictive for high OS level in HF patients.Eccentric cardiac remodeling, MR severity and PAH severity are independent predictors of OS in HF patients.

Role of oxidative stress in left ventricular remodeling and heart failure after myocardial infarction

1999 ◽  
Vol 5 (3) ◽  
pp. 79
Author(s):  
Shintaro Kinugawa ◽  
Hiroyuki Tsutsui ◽  
Tomomi Ide ◽  
Hideo Ustumi ◽  
Nobuhiro Suematsu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular

Importance of antioxidant and antiapoptotic effects of β-receptor blockers in heart failure therapy

2004 ◽  
Vol 287 (3) ◽  
pp. H1003-H1012 ◽  
Author(s):  
Keisuke Kawai ◽  
Fuzhong Qin ◽  
Junya Shite ◽  
Weike Mao ◽  
Shuji Fukuoka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Cardiac Pacing ◽  
Left Ventricular ◽  
Beneficial Effects ◽  
Myocyte Apoptosis ◽  
Adrenergic Blocking ◽  
Fractional Shortening

The present study was carried out to determine whether beneficial effects of carvedilol in congestive heart failure (CHF) are mediated via its β-adrenergic blocking, antioxidant, and/or α-adrenergic blocking action. Rabbits with heart failure induced by rapid cardiac pacing were randomized to receive subcutaneous carvedilol, metoprolol, propranolol plus doxazosin, or placebo pellets for 8 wk and compared with sham-operated rabbits without pacing. We found rapid cardiac pacing produced clinical heart failure, left ventricular dilation, and decline of left ventricular fractional shortening. This was associated with an increase in left ventricular end-diastolic pressure, decrease in left ventricular first derivative of left ventricular pressure, and myocyte hypertrophy. Tissue oxidative stress measured by GSH/GSSG was increased in the heart with increased oxidation product of mitochondrial DNA, 8-oxo-7,8-dihydro-2′-deoxyguanosine, increase of Bax, decrease of Bcl-2, and increase of apoptotic myocytes as measured by anti-single-stranded DNA monoclonal antibody. Administration of carvedilol and metoprolol, which had no effect in sham animals, attenuated cardiac ventricular remodeling, cardiac hypertrophy, oxidative stress, and myocyte apoptosis in CHF. In contrast, propranolol plus doxazosin, which has less antioxidant effects, produced smaller effects on left ventricular function and myocyte apoptosis. In all animals, GSH/GSSG correlated significantly with changes of left ventricular end-diastolic dimension ( r = −0.678, P < 0.0001), fractional shortening ( r = 0.706, P < 0.0001), and apoptotic myocytes ( r = −0.473, P = 0.0001). Thus our findings suggest antioxidant and antiapoptotic actions of carvedilol and metoprolol are important determinants of clinical beneficial effects of β-receptors in the treatment of CHF.

scholarly journals Tolerogenic dendritic cells induced by atorvastatin via inhibition of the TLR-4/NF-κB pathway improve cardiac remodeling after myocardial infarction

2020 ◽  
Author(s):  
Jianbing Zhu ◽  
Hang Chen ◽  
Yuanji Ma ◽  
Haibo Liu ◽  
Zhaoyang Chen
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Infarct Size ◽  
Inflammatory Reaction ◽  
Ventricular Remodeling ◽  
Inflammatory Responses ◽  
Systolic Function ◽  
Left Ventricular

Abstract BackgroundNecrosis of ischemic cardiomyocytes after myocardial infarction (MI) activates an intense inflammatory reaction. Dendritic cells (DCs) play a crucial role in the repair process after MI. Tolerogenic DCs (tDCs) can inhibit inflammatory responses. Methods and resultsWe investigated the role of atorvastatin and supernatants of necrotic cardiomyocytes (SNC) on DCs. We found that SNC induced DCs maturation, activated TLR-4/NF-κB pathway, promoted inflammatory cytokines secretion and oxidative stress. Co-treatment with SNC and atorvastatin suppressed DC maturation and inflammatory response, which meant that atorvastatin induced DCs tolerate to SNC. Then, we investigated the effect of mDCs induced by SNC and tDCs induced by atorvastatin on ventricular remodeling after MI. tDCs treatment significantly improved the left ventricular systolic function, reduced the infiltration of MPO+ neutrophil, Mac3+ macrophages and CD3+ T cells, inhibited myocardial apoptosis and fibrosis, and decreased infarct size. Compared with PBS, treatment with mDCs did not showed beneficial effect on ventricular remodeling and inflammatory reaction after MI in mice.ConclusionAtorvastatin inactivated the TLR-4/NF-κB pathway, repressed the oxidative stress, inflammatory response, and immune maturity induced by SNC. Treatment with tDCs, induced by co-treated with atorvastatin, preserved left ventricular function, limited infarct size, suppressed the infiltration of inflammatory cells, and attenuated the severity of fibrosis, and reduced the number of apoptotic cardiomyocytes.

scholarly journals Risk Factors Contributing to the Progression of Paroxysmal and Persistent Atrial Fibrillation in Heart Failure Patients with Mid-Range Ejection Fraction

2021 ◽  
Author(s):  
Lusine Hazarapetyan ◽  
Lyudmila Budaghyan ◽  
Alina Maloyan ◽  
Svetlana Grigoryan
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Transforming Growth Factor ◽  
Ventricular Remodeling ◽  
Hypertensive Crisis ◽  
Left Ventricular ◽  
Control Group ◽  
Increased Risk

Aims: Heart failure (HF) is frequently accompanied by atrial fibrillation (AF), a combination that worsens the outcomes of both diseases. Despite advances in the treatment of AF, it remains a serious and unsolved problem for clinicians and researchers. The aim of this study was to examine risk factors for incidents of paroxysmal and persistent AF in patients having heart failure with mid-range ejection fraction (HFmrEF). Methods. Overall, 71 patients with HFmrEF and non-valvular AF, including paroxysmal and persistent types, were enrolled in this study. As a control group, 42 HFmrEF patients without AF were also enrolled. All patients underwent detailed physical examination, including resting electrocardiography, echocardiography, and 24-hour ambulatory Holter monitoring. Levels of the inflammation markers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) and the fibrotic marker transforming growth factor-β1 (TGF-β1) were measured by ELISA and expressed as odds ratios. Results: We show that paroxysmal AF was associated with higher diastolic blood pressure, whereas both paroxysmal and persistent forms of AF were associated with more frequent occurrence of hypertensive crisis episodes and greater body mass index. Progression from paroxysmal to persistent AF was associated with significant ventricular remodeling. Persistent and paroxysmal AF were associated with higher levels of inflammatory markers when compared to HFmrEF patients having no AF. In addition, TGF-1 was significantly increased in HFmrEF patients having persistent but not paroxysmal AF. Conclusions: Occurrence of AF, first paroxysmal and then persistent, in HFmrEF patients is associated with left ventricular remodeling and the appearance of systemic inflammatory and fibrotic markers. Changes in those parameters may be indicators by which to identify patients at increased risk of atrial fibrillation. Further studies are needed to determine the prognostic validity of these markers.

Effects of Prolonged Propranolol Treatment on Left Ventricular Remodeling and Oxidative Stress After Myocardial Infarction in Rats

2000 ◽  
Vol 35 (5) ◽  
pp. 806-813 ◽  
Author(s):  
Pascale Mansuy ◽  
Nathalie Mougenot ◽  
Juan Fernando Ramirez-Gil ◽  
Dominique Bonnefont-Rousselot ◽  
Françoise Raillecove ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Propranolol Treatment ◽  
And Oxidative Stress

scholarly journals Antioxidant Vitamins Reduce Oxidative Stress and Ventricular Remodeling in Patients with Acute Myocardial Infarction

2005 ◽  
Vol 18 (3) ◽  
pp. 487-496 ◽  
Author(s):  
C. Gasparetto ◽  
A. Malinverno ◽  
D. Culacciati ◽  
D. Gritt ◽  
P.G. Prosperini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Reactive Oxygen ◽  
Total Antioxidant Status ◽  
Left Ventricular ◽  
Antioxidant Vitamins ◽  
Reactive Oxygen Metabolites ◽  
Oxygen Metabolites

We analyzed soluble vascular adhesion molecules (sVCAM-1), reactive oxygen metabolites (ROMs) level, total antioxidant status (TAS) and telediastolic left ventricular volume (TLW) in patients with myocardial infarction undergoing reperfusion therapy and treated with antioxidant vitamins (AT) or placebo (P) before and for 1 month after reperfusion. After reperfusion, sVCAM-1 serum concentration, reactive oxygen metabolites level, and TLW were significantly higher in patients treated with placebo than in those treated with antioxidant vitamins, while TAS was significantly higher in patients treated with antioxidant supplementation. We observed that 48 hours after reperfusion sVCAM-1 (P) vs sVCAM −1(AT) was 2.03±0.5 vs 1.63±0.7 μg/ml with p<0.01; ROMs (P) vs ROMs (AT) were 335.60±35.80 vs 307.50±47.10 U.CARR with p<0.05; TAS (P) vs TAS (AT) was 526.47±44.24 vs 737.65±51.15 μmol/l with p<0.01; 1 week after reperfusion TLW (P) vs TLW (AT) was 125.12±29.80 vs 119.40±29.40 ml with p<0.05; 1 month after reperfusion TLW (P) vs TLW (AV) was 132.00±33.50 vs 123.40±21.60 ml with p<0.05. In the first period after infarction, vitamin treatment improves the antioxidant system and reduces oxidative stress, inflammatory process and left ventricular remodeling.

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