Abstract 740: Statin Prevents Structural and Electrical Atrial Remodeling in Rat Hypertensive Heart Failure Induced by Chronic Inhibition of NO Synthesis

Background: The prevalence of atrial fibrillation (AF) increases in patients with hypertension and heart failure in which endothelial function is impaired. Oxidative stress in atrial tissues is involved in the development of AF. Statins have pleiotropic effects including antioxidant effects. Thus, we developed hypertensive heart failure in rats by the chronic inhibition of NO synthesis and we investigated the role of the statin in atrial remodeling. Methods and Results: Ten-week-old male Wistar-Kyoto rats were randomly divided into four groups: the control (no treatment), the L-NAME (received L-NAME, an inhibitor of NO synthase, 1 g/L in drinking water), the L-NAME+atorvastatin (L(a low dose)) (5 mg/kg/day) and the L-NAME+atorvastatin (H(a high dose)) (20 mg/kg/day). Chronic inhibition of NO synthesis increased systolic blood pressure (control group: 138±5 mmHg; L-NAME group: 212±8 mmHg L+atorvastatin (L) group: 210±6 seconds , L+atorvastatin (H): 208±6 seconds) and decreased LV dP/dt max/LVSP (control group: 54±3, L-NAME group: 36±8, L+atorvastatin (L) group: 40±3, L+atorvastatin (H) group: 38±6 1/second), whereas co-administration of atorvastatin did not affect them. The sustained duration of AF was always induced by transesophageal burst pacing (The pacing pulse used for induction of AF was rectanglar in shape, of 60V and 6ms-width. The atrium was paced at a cycle length of 12ms (83Hz) for 30seconds) and it was prolonged by L-NAME, which was prevented by atorvastatin in a dose-dependent manner (control: 8.8 ± 1.0 seconds, L-NAME: 20.7 ± 3.0 seconds, L+atorvastatin (L): 12.8 ± 3.2 seconds , L+atorvastatin (H): 8.8 ± 2.6 seconds). The chronic inhibition of NO synthesis increased the extent of fibrosis and markers of oxidative stresses such as proteins modified with 4-hydroxy-trans-2-nonenal and p47phox and rac1 in left atrial tissue, either of which was prevented by atorvastatin. Conclusion: Atorvastatin attenuates oxidative stresses in atrium and prevents atrial electrical and morphological remodeling in rat hypertensive failing hearts without hemodynamic changes. Statin may be beneficial in patients with coronary heart disease and atrial fibrillation, and may contribute to the prevention of the onset of heart failure.

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THE ROLE OF INFLAMMATION AND COAGULATION CASCADE IN THE PATHOGENESIS OF ATRIAL FIBRILLATION

ASJ. ◽

10.31618/asj.2707-9864.2020.3.41.32 ◽

2020 ◽

Vol 3 (41) ◽

pp. 8-10

Author(s):

L. Hazarapetyan ◽

S. Grigoryan ◽

A. Sarksyan

Keyword(s):

Atrial Fibrillation ◽

Coagulation Cascade ◽

Control Group ◽

Atrial Remodeling ◽

Inflammation Markers ◽

Reactive Protein ◽

Gender And Age ◽

The Impact ◽

The Relationship

Introduction: Atrial fibrillation (AF) is associated with prothrombotic or hypercoagulable states, various inflammation markers such as interleukin-6 (IL-6) and hsC-reactive protein (hsCRP) have also been associated with AF. The aim of this study is to investigate the relationship between inflammation markers and the prothrombotic state in the setting of AF and the impact on outcome in patients with AF. Methods: We observed 141 patients with non-valvular AF. As a control group patients similar in gender and age without AF were examined. Clinical, instrumental and laboratory tests were performed on the observed patients. The markers of the coagulation cascade (TF and F) and of inflammatory markers (hsCRP and IL-6) were studied additionally by ELISA on the analyzer "Stat Fax 303 Plus". Studies were conducted using SPSS 13.0 and EXCEL-2013. Results: The obtained results showed that compared to the control group, AF patients had significantly higher levels of IL-6 (p = 0.043), hsCRP (p = 0.002), TF (p = 0.026), and F (p = 0.025). Moreover, levels of hsCRP were higher among AF patients at "high" risk of stroke by CHA2DS2-VASc Score (p = 0.003). Besides, the levels of hsCRP and IL-6 were markedly elevated in patients with dilated left atrium (p = 0.001), poorly functioning left atrial appendage (p = 0.023) and longer duration of AF (p = 0.002). Conclusion: We have demonstrated that the increased plasma levels of IL-6 and hsCRP are related to indices of the coagulation cascade and contribute to structural atrial remodeling in patients with AF.

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THE NEW GENETIC ASPECTS OF ATRIAL FIBRILLATION IN PERSONS OF THE RUSSIAN POPULATION

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2020-22-12-27-33 ◽

2020 ◽

pp. 27-33

Author(s):

Aksyutina N.V. ◽

Shulman V.A. ◽

Aldanova E.E. ◽

Nikulina S.Yu. ◽

Mordovskii V.S. ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Chronic Heart Failure ◽

Molecular Genetic ◽

Genetic Research ◽

Heart Rhythm ◽

Control Group ◽

Atrial Remodeling ◽

Cardiovascular Pathology ◽

Heart Rhythm Disorders

Atrial fibrillation (AF) is one of the most common and dangerous heart rhythm disorders. Lone AF is due to a genetic predisposition. Foreign studies have proven the association of rs2200733 polymorphism of chromosome 4q25 with AF. No such studies have been conducted in the Russian Federation. Purpose of the study: to determine the association of the rs2200733 polymorphism of chromosome 4q25 with the development of AF, and to exclude the possible connection of the studied polymorphic marker with concomitant cardiovascular pathology. A total of 247 patients with AF were examined (113 from lone AF, 134 from secondary). Control group - 182 healthy people. Behavior: ECG, EchoCG, Holter ECG monitoring, blood test for thyroid hormones, VEM, CAG, molecular genetic research. In the group of patients with AF, the TT genotype was detected in 12.95%, which is statistically significant more often than in the control group (4.94%), p<0.05. In the presence of a genotype with a rare T allele, the risk of developing AF increases by 1.5 times. The TT genotype was statistically significant more often in the subgroup of patients with isolated AF (17.70%) in comparison with the control group (4.94%), p<0.05. The risk of developing isolated AF in the presence of a genotype with a rare allele T is 1.8 times increased. Chronic heart failure, no statistically significant differences were found (p>0.05). In patients with the TT genotype, the mean LA size was 3.738 ± 0.494 cm, it was statistically significantly smaller than in patients with the CC genotype, which corresponded to 3.925 ± 0.629 cm, p<0.05; and than in individuals with a heterozygous CT genotype, its value in this subgroup is 4.018 ± 0.639 cm, p<0.05. Conclusions: Homozygous genotype for the rare TT allele and the T allele of the rs2200733 polymorphism of chromosome 4q25 are predictors of lone AF. The rs2200733 polymorphism has no association with any cardiovascular pathology, such as hypertension, ischemic heart disease and chronic heart failure. The TT genotype and the T allele of the rs2200733 polymorphism do not affect left atrial remodeling in patients with AF.

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Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats

Cardiovascular Diabetology ◽

10.1186/s12933-019-0964-4 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 21

Author(s):

Qingmiao Shao ◽

Lei Meng ◽

Sharen Lee ◽

Gary Tse ◽

Mengqi Gong ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Mitochondrial Biogenesis ◽

Mitochondrial Function ◽

High Fat Diet ◽

Low Dose ◽

Control Group ◽

High Dose ◽

Atrial Remodeling ◽

High Fat

Abstract Background Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus (T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model. Methods High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks. Results Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway. Conclusions Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation.

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Role of Metoprolol Succinate in the Treatment of Heart Failure and Atrial Fibrillation

American Journal of Therapeutics ◽

10.1097/mjt.0000000000001043 ◽

2020 ◽

Vol 27 (2) ◽

pp. e183-e193

Author(s):

Dragos Vinereanu ◽

Jindrich Spinar ◽

Atul Pathak ◽

Dariusz Kozlowski

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Metoprolol Succinate

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Interleukin-6 Could Be a Potential Prognostic Factor in Ambulatory Elderly Patients with Stable Heart Failure: Results from a Pilot Study

Journal of Clinical Medicine ◽

10.3390/jcm10030504 ◽

2021 ◽

Vol 10 (3) ◽

pp. 504

Author(s):

Marina Povar-Echeverría ◽

Pablo Esteban Auquilla-Clavijo ◽

Emmanuel Andrès ◽

Francisco Javier Martin-Sánchez ◽

María Victoria Laguna-Calle ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Renal Failure ◽

Interleukin 6 ◽

Kaplan Meier ◽

Patients With Heart Failure ◽

Potential Prognostic Factor ◽

Fundamental Phenomenon ◽

Group 2

Introduction: Inflammation is a fundamental phenomenon in heart failure, but the prognostic or therapeutic role of markers such as interleukin-6 (IL-6) has not yet been clarified. The objective of this study is to describe the clinical profile of patients with elevated IL-6 and determine if they have worse clinical outcomes. Methods: A retrospective c.ohort observational study including 78 patients with heart failure followed up at the Heart Failure Outpatient Clinic of the Internal Medicine Department. IL-6 was determined in all patients, who were then assigned into two groups according to IL-6 level (normal or high). Clinical and prognostic data were collected to determine the differences in both groups. Results: The average age was 79 years, 60% female. A total of 53.8% of the patients had elevated IL-6 (group 2). Patients with elevated IL-6 presented more frequently with anemia mellitus (64.3% vs. 41.7%; p = 0.046), atrial fibrillation (83.3% vs. 61.9% p = 0.036), dyslipidemia (76.2% vs. 58.2%; p = 0.03), higher creatinine levels (1.35 mg/dL vs. 1.08 mg/dL; p = 0.024), lower glomerular filtration rate (43.6 mL/min/m2 vs. 59.9 mL/min/m2; p = 0.007), and anemia 25% vs. 52.4% p = 0.014. The factors independently associated with the increase in IL-6 were anemia 3.513 (1.163–10.607) and renal failure 0.963 (0.936–0.991), p < 0.05. Mortality was higher in the group with elevated IL-6 levels (16% vs. 2%; p = 0.044) with a log-rank p = 0.027 in the Kaplan–Meier curve. Conclusion: Patients with heart failure and elevated IL-6 most often have atrial fibrillation, diabetes mellitus, dyslipidemia, anemia, and renal failure. In addition, mortality was higher and a tendency of higher hospital admission was observed in stable HF patients with elevated IL-6.

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Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽

10.3390/pharmaceutics13030386 ◽

2021 ◽

Vol 13 (3) ◽

pp. 386

Author(s):

Tung-Hu Tsai ◽

Yu-Jen Chen ◽

Li-Ying Wang ◽

Chen-Hsi Hsieh

Keyword(s):

Stereotactic Body Radiation Therapy ◽

In Vivo Studies ◽

Control Group ◽

High Dose ◽

Dependent Manner ◽

Hep G2 ◽

Time Curve ◽

Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

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PROGNOSTIC ROLE OF ATRIAL FIBRILLATION AND HEART RATE CONTROL IN CHRONIC HEART FAILURE PATIENTS

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(13)60735-4 ◽

2013 ◽

Vol 61 (10) ◽

pp. E735

Author(s):

Savina Nodari ◽

Marco Triggiani ◽

Laura Lupi ◽

Alessandra Manerba ◽

Giuseppe Milesi ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Heart Rate ◽

Chronic Heart Failure ◽

Rate Control ◽

Heart Rate Control ◽

Prognostic Role ◽

Heart Failure Patients

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Role of Heart Failure and Infectious Etiology in Infective Endocarditis With New-Onset Atrial Fibrillation

The American Journal of Cardiology ◽

10.1016/j.amjcard.2015.12.019 ◽

2016 ◽

Vol 117 (6) ◽

pp. 1028

Author(s):

Saraschandra Vallabhajosyula ◽

Daniel C. DeSimone ◽

Nandan S. Anavekar

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Infective Endocarditis ◽

Onset Atrial Fibrillation ◽

Infectious Etiology ◽

New Onset

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The Anti-Inflammatory Potential of Mimosa caesalpiniifolia Following Experimental Colitis: Role of COX-2 and TNF-Alpha Expression

Drug Research ◽

10.1055/s-0043-119750 ◽

2017 ◽

Vol 68 (04) ◽

pp. 196-204 ◽

Cited By ~ 3

Author(s):

Marcelo Silva ◽

Wagner Vilegas ◽

Marcelo da Silva ◽

Ana Paiotti ◽

Mauricio Pastrelo ◽

...

Keyword(s):

Protective Action ◽

Experimental Colitis ◽

Distal Colon ◽

Tnf Alpha ◽

High Dose ◽

Dependent Manner ◽

Hydroalcoholic Extract ◽

Tnf Α ◽

Cox 2

AbstractThe aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 – Sham group:; G2 – TNBS group; G3, G4 –colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 – colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner.

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