scholarly journals Cardioprotective Effect of Resveratrol in a Postinfarction Heart Failure Model

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Adam Riba ◽  
Laszlo Deres ◽  
Balazs Sumegi ◽  
Kalman Toth ◽  
Eszter Szabados ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
P38 Mapk ◽  
Left Ventricular ◽  
Failure Model ◽  
Major Health Problem ◽  
Ros Formation ◽  
Cox 2 ◽  
Heart Failure Model

Despite great advances in therapies observed during the last decades, heart failure (HF) remained a major health problem in western countries. In order to further improve symptoms and survival in patients with heart failure, novel therapeutic strategies are needed. In some animal models of HF resveratrol (RES), it was able to prevent cardiac hypertrophy, contractile dysfunction, and remodeling. Several molecular mechanisms are thought to be involved in its protective effects, such as inhibition of prohypertrophic signaling molecules, improvement of myocardial Ca2+ handling, regulation of autophagy, and the reduction of oxidative stress and inflammation. In our present study, we wished to further examine the effects of RES on prosurvival (Akt-1, GSK-3β) and stress signaling (p38-MAPK, ERK 1/2, and MKP-1) pathways, on oxidative stress (iNOS, COX-2 activity, and ROS formation), and ultimately on left ventricular function, hypertrophy and fibrosis in a murine, and isoproterenol- (ISO-) induced postinfarction heart failure model. RES treatment improved left ventricle function, decreased interstitial fibrosis, cardiac hypertrophy, and the level of plasma BNP induced by ISO treatment. ISO also increased the activation of P38-MAPK, ERK1/2Thr183-Tyr185, COX-2, iNOS, and ROS formation and decreased the phosphorylation of Akt-1, GSK-3β, and MKP-1, which were favorably influenced by RES. According to our results, regulation of these pathways may also contribute to the beneficial effects of RES in HF.

scholarly journals Modulation of Mitochondrial Quality Control Processes by BGP-15 in Oxidative Stress Scenarios: From Cell Culture to Heart Failure

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Orsolya Horvath ◽  
Katalin Ordog ◽  
Kitti Bruszt ◽  
Nikoletta Kalman ◽  
Dominika Kovacs ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Hydrogen Peroxide ◽  
Quality Control ◽  
Mitochondrial Fusion ◽  
Neonatal Rat ◽  
Failure Model ◽  
Mitochondrial Quality Control ◽  
Insulin Sensitizer ◽  
Heart Failure Model

Heart failure (HF) is a complex chronic clinical disease characterized by among others the damage of the mitochondrial network. The disruption of the mitochondrial quality control and the imbalance in fusion-fission processes lead to a lack of energy supply and, finally, to cell death. BGP-15 (O-[3-piperidino-2-hydroxy-1-propyl]-nicotinic acid amidoxime dihydrochloride) is an insulin sensitizer molecule and has a cytoprotective effect in a wide variety of experimental models. In our recent work, we aimed to clarify the mitochondrial protective effects of BGP-15 in a hypertension-induced heart failure model and “in vitro.” Spontaneously hypertensive rats (SHRs) received BGP-15 or placebo for 18 weeks. BGP-15 treatment preserved the normal mitochondrial ultrastructure and enhanced the mitochondrial fusion. Neonatal rat cardiomyocytes (NRCMs) were stressed by hydrogen-peroxide. BGP-15 treatment inhibited the mitochondrial fission processes, promoted mitochondrial fusion, maintained the integrity of the mitochondrial genome, and moreover enhanced the de novo biogenesis of the mitochondria. As a result of these effects, BGP-15 treatment also supports the maintenance of mitochondrial function through the preservation of the mitochondrial structure during hydrogen peroxide-induced oxidative stress as well as in an “in vivo” heart failure model. It offers the possibility, which pharmacological modulation of mitochondrial quality control under oxidative stress could be a novel therapeutic approach in heart failure.

scholarly journals Reversal of heart failure in a chemogenetic model of persistent cardiac redox stress

2019 ◽  
Vol 317 (3) ◽  
pp. H617-H626 ◽  
Author(s):  
Andrea Sorrentino ◽  
Benjamin Steinhorn ◽  
Luca Troncone ◽  
Seyed Soheil Saeedi Saravi ◽  
Sachin Badole ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Myocyte ◽  
Ang Ii ◽  
Failure Model ◽  
Redox Stress ◽  
Amino Acid Oxidase ◽  
Chronic Oxidative Stress ◽  
Metabolic Remodeling ◽  
Heart Failure Model

We previously described a novel “chemogenetic” animal model of heart failure that recapitulates a characteristic feature commonly found in human heart failure: chronic oxidative stress. This heart failure model uses a chemogenetic approach to activate a recombinant yeast d-amino acid oxidase in rat hearts in vivo to generate oxidative stress, which then rapidly leads to the development of a dilated cardiomyopathy. Here we apply this new model to drug testing by studying its response to treatment with the angiotensin II (ANG II) receptor blocker valsartan, administered either alone or with the neprilysin inhibitor sacubitril. Echocardiographic and [18F]fluorodeoxyglucose positron emission tomographic imaging revealed that valsartan in the presence or absence of sacubitril reverses the anatomical and metabolic remodeling induced by chronic oxidative stress. Markers of oxidative stress, mitochondrial function, and apoptosis, as well as classical heart failure biomarkers, also normalized following drug treatments despite the persistence of cardiac fibrosis. These findings provide evidence that chemogenetic heart failure is rapidly reversible by drug treatment, setting the stage for the study of novel heart failure therapeutics in this model. The ability of ANG II blockade and neprilysin inhibition to reverse heart failure induced by chronic oxidative stress identifies a central role for cardiac myocyte angiotensin receptors in the pathobiology of cardiac dysfunction caused by oxidative stress. NEW & NOTEWORTHY The chemogenetic approach allows us to distinguish cardiac myocyte-specific pathology from the pleiotropic changes that are characteristic of other “interventional” animal models of heart failure. These features of the chemogenetic heart failure model facilitate the analysis of drug effects on the progression and regression of ventricular remodeling, fibrosis, and dysfunctional signal transduction. Chemogenetic approaches will be highly informative in the study of the roles of redox stress in heart failure providing an opportunity for the identification of novel therapeutic targets.

scholarly journals Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model

2016 ◽  
Vol 37 (4) ◽  
pp. 473-482 ◽  
Author(s):  
Chun-kai Huang ◽  
Bi-yi Chen ◽  
Ang Guo ◽  
Rong Chen ◽  
Yan-qi Zhu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Failure Model ◽  
Heart Failure Model

scholarly journals Synthesis of new azaindeno-acetonitrile derivative with inotropic activity against heart failure model

2019 ◽  
Vol 9 (6) ◽  
pp. 4598-4604
Keyword(s):  
Heart Failure ◽  
Biological Activity ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Failure Model ◽  
Inotropic Activity ◽  
Inotropic Drugs ◽  
Heart Failure Model ◽  
Steroid Derivative

Several steroid derivatives have prepared as inotropic drugs; however, there are few reports on azaindeno-steroid derivatives with inotropic activity. The objective of this investigation was to prepare some azaindeno-acetonitrile derivatives (compounds 3 to 7) to evaluate their biological activity on left ventricular pressure. The first step was achieved by preparation of azaindeno-steroid derivatives using reactions of etherification and addition. The second stage involves the evaluation of biological activity from azaindeno-steroid derivatives on left ventricular pressure in a heart failure model using either estrone or an enone-steroid derivative (compound 2) as controls. The results showed that only compound 6 increases left ventricular pressure compared with estrone, compounds 2-5 and 6. In conclusion, the positive inotropic effect exerted by compound 6 depends on the functional groups involved in its chemical structure.

Abstract 134: Influence of Predictive Modeling in Implementing Optimal Heart Failure Therapy in Inpatient setting

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Hari Prasad ◽  
Gujan Choudhary ◽  
Ali Fahad ◽  
Dwight Stapleton
Keyword(s):  
Heart Failure ◽  
Medical Therapy ◽  
Systolic Heart Failure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Failure Model ◽  
Heart Failure Therapy ◽  
Device Therapy ◽  
Predictive Tool ◽  
Heart Failure Model

Background: A gap remains between evidence-based guidelines in the treatment of heart failure and current pharmacologic and device therapy. The Seattle Heart Failure Model is an accurate predictive tool that allows the clinician to quantitatively assess the influence of pharmacologic and device therapy on heart failure that has been validated in outpatient setting. We attempt to use the Seattle Heart Failure Model in optimizing the heart failure therapy. Methods: We examined 405 patients’ charts who were admitted with a diagnosis of acute systolic heart failure or acute on chronic systolic heart failure with left ventricular ejection fraction ≤ 40%. Twenty-one data elements were entered into the Seattle Heart Failure Model to create a survival estimate before and after implementation of interventions known to be beneficial, both pharmacologic (addition of ACE/ARB, statin, β-blocker, aldosterone blocker) and device-based (consideration for AICD, BiV pacer, BiV ICD). Results: The mean age of the population examined was 77 ± 9 years. The cohort was comprised of 72 % males, mean weight 89 ± 22.5kg, with NYHA class 2.4 ± 0.6 symptoms. Ischemic etiology was identified in 86% with a mean left ventricular EF of 29.8 ± 9 %. Laboratory data included mean Hgb 10.1 ±1.5g/dL with 15 ± 8% lymphocytes, mean total cholesterol of 176 ± 42mg/dL and mean sodium of 133 ± 3.5mmol/L. The one year all-cause mortality rates were 19.5 % reflecting advanced heart failure population. In the 405 patients examined, we were able to alter therapy (medical or device) in 86%. This included advancement of medical therapy in 56%, consideration for device referral in 11%, or both (medical therapy and device referral) in 19 %. This augmentation of therapy resulted in an increase in estimated mean life expectancy from 6.6 years to 9.6 years (p < 0.001). Conclusion: Use of the Seattle Heart Failure Model significantly helps in intensification of heart failure therapy when applied at time of discharge or in first follow up visit post discharge.

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