scholarly journals TVP1022 Attenuates Cardiac Remodeling and Kidney Dysfunction in Experimental Volume Overload-Induced Congestive Heart Failure

2011 ◽  
Vol 4 (4) ◽  
pp. 463-473 ◽  
Author(s):  
Zaid A. Abassi ◽  
Yaron D. Barac ◽  
Sawa Kostin ◽  
Ariel Roguin ◽  
Elena Ovcharenko ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Remodeling ◽  
Volume Overload ◽  
Kidney Dysfunction

Abstract 375: Mechanotransduction via Titin’s N2B Element Contributes to Cardiac Remodeling

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Mathew Bull ◽  
Pooja Nair ◽  
Joshua Strom ◽  
Michael Gotthardt ◽  
Henk Granzier
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Mapk Pathway ◽  
Hot Spot ◽  
Pressure Overload ◽  
Volume Overload ◽  
Mitogen Activated Protein Kinase ◽  
Stress And Strain ◽  
Knock Out ◽  
Voluntary Running

Pathological remodeling is responsible for the functional deficits characteristic of heart failure patients. Understanding mechanotransduction is limited, but holds potential to provide novel therapeutic targets to treat patients with heart failure, especially those with diastolic dysfunction and preserved ejection fraction (HFpEF). Titin is the largest known protein and is abundant in muscle. It is the main contributor of passive stiffness in the heart and functions as a molecular mechano-sensor for stress and strain in the myocyte. Titin is composed of four distinct regions, (N-terminal Z-line, I-band, A-band, and C-terminal M-line), and acts as a molecular spring that is responsible for the assembly and maintenance of ultrastructure in the sarcomere. The elastic N2B element found in titin’s I-band region has been proposed as a mechano-sensor and signaling “hot spot” in the sarcomere. This study investigates the role of titin’s cardiac specific N2B element as sensor for stress and strain induced remodeling in the heart. The previously published N2B knock out (KO) mouse was subjected to a variety of stressors including transverse aortic constriction (TAC), aorto-caval fistula (ACF), chronic swimming, voluntary running and isoproterenol injections. Through chronic pathologic stress, pressure overload (TAC) and chronic volume overload (ACF), we found that the N2B element is necessary for the response to volume overload but not pressure overload as determined by changes in cardiac remodeling. Furthermore, the response to exercise either by chronic swimming or voluntary running was reduced in the N2B KO mouse. Finally, unlike the wild-type (WT) mouse, the N2B KO mouse did not respond to isoproterenol injections with hypertrophic remodeling. Ongoing work to elucidate the molecular pathways involving the N2B element and response to stress, is focused on its binding protein Four-and-a-half-LIM domains 2 (FHL2) and the mitogen activated protein kinase (MAPK) pathway. Taken together our data suggest that the N2B element contributes significantly to mechanotransduction in the heart.

scholarly journals Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0184161 ◽  
Author(s):  
Mohammed Shaqura ◽  
Doaa M. Mohamed ◽  
Noureddin B. Aboryag ◽  
Lama Bedewi ◽  
Lukas Dehe ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Liver Injury ◽  
Volume Overload

scholarly journals Blood lactate increases with the progression of mitral valve disease in dogs

2018 ◽  
Vol 38 (9) ◽  
pp. 1781-1786
Author(s):  
Jorge Cardoso Silva-Filho ◽  
Marlos G. Sousa ◽  
Evandro Zacché Pereira ◽  
Edna M.G. Ortiz ◽  
Rodrigo P. Franco ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Mitral Valve ◽  
Blood Lactate ◽  
Cardiac Remodeling ◽  
Mitral Valve Disease ◽  
Lactate Concentration ◽  
Tissue Perfusion ◽  
Valve Disease ◽  
Cross Sectional

ABSTRACT: In dogs with congestive heart failure, the upregulated sympathetic tone causes vasoconstriction that impairs peripheral blood supply, therefore causing the accumulation of lactate. In this prospective cross-sectional study with a longitudinal component, blood lactate was quantified in 10 healthy and 34 myxomatous mitral valve disease (MMVD) dogs to investigate its potential use as a diagnostic and prognostic biomarker. While there were no differences in lactate concentration between control animals and stages B1 (3.31±0.62mmol/L) and B2 (3.32±0.46mmol/L) dogs, significant differences were found between healthy (2.50±0.69mmol/L) and both C (3.99±0.47mmol/L) and D (6.97±1.23mmol/L) animals. When a cut-off of 3.35mmol/L was used, lactate was able to distinguish dogs with normal and remodeled hearts with a sensitivity of 78.2% and specificity of 63.6%. Also, significant correlations existed between lactate and indicators of cardiac remodeling. Finally, animals with blood lactate <3.5mmol/L carried a better prognosis when compared with dogs in which lactate was >5.0mmol/L. Our results suggest that the progression of MMVD results in accumulation of lactate within the bloodstream, which is likely attributable to the impaired peripheral tissue perfusion. In MMVD dogs, blood lactate may be used as a surrogate for cardiac remodeling, and an increased concentration is associated with a worse prognosis regarding the time to evolve into congestive heart failure.

Efficacy of Add-on low Dose Versus High Dose of Tolvaptan to Furosemide on Congestive Heart Failure with Advanced Kidney Dysfunction

2017 ◽  
Vol 23 (10) ◽  
pp. S64
Author(s):  
Keisuke Kida ◽  
Shunichi Doi ◽  
Chikayuki Ito ◽  
Norio Suzuki ◽  
Kohei Ashikaga ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Low Dose ◽  
High Dose ◽  
Kidney Dysfunction

scholarly journals A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Leonardo Schirone ◽  
Maurizio Forte ◽  
Silvia Palmerio ◽  
Derek Yee ◽  
Cristina Nocella ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
Volume Overload ◽  
Cardiac Complications ◽  
Compensatory Mechanism ◽  
Myocardial Remodeling ◽  
Heart Failure Progression ◽  
Complex Signaling

Pathological molecular mechanisms involved in myocardial remodeling contribute to alter the existing structure of the heart, leading to cardiac dysfunction. Among the complex signaling network that characterizes myocardial remodeling, the distinct processes are myocyte loss, cardiac hypertrophy, alteration of extracellular matrix homeostasis, fibrosis, defective autophagy, metabolic abnormalities, and mitochondrial dysfunction. Several pathophysiological stimuli, such as pressure and volume overload, trigger the remodeling cascade, a process that initially confers protection to the heart as a compensatory mechanism. Yet chronic inflammation after myocardial infarction also leads to cardiac remodeling that, when prolonged, leads to heart failure progression. Here, we review the molecular pathways involved in cardiac remodeling, with particular emphasis on those associated with myocardial infarction. A better understanding of cell signaling involved in cardiac remodeling may support the development of new therapeutic strategies towards the treatment of heart failure and reduction of cardiac complications. We will also discuss data derived from gene therapy approaches for modulating key mediators of cardiac remodeling.

Exogenous midkine administration prevents cardiac remodeling in pacing-induced congestive heart failure of rabbits

2014 ◽  
Vol 31 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Masahide Harada ◽  
Mayumi Hojo ◽  
Kaichiro Kamiya ◽  
Kenji Kadomatsu ◽  
Toyoaki Murohara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Remodeling

scholarly journals Mechanical work and energetic analysis of eccentric cardiac remodeling in a volume overload heart failure in rats

2009 ◽  
Vol 296 (4) ◽  
pp. H1117-H1124 ◽  
Author(s):  
Yoshiaki Takewa ◽  
Elie R. Chemaly ◽  
Miyako Takaki ◽  
Li Fan Liang ◽  
Hongwei Jin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Sham Group ◽  
Group Versus ◽  
Volume Overload ◽  
Left Ventricular ◽  
Mechanical Work ◽  
Energy Utilization ◽  
Male Rats ◽  
Sham Operation

Eccentric cardiac remodeling seen in dilated cardiomyopathy or regurgitant valvular disease is a well-known process of heart failure progression, but its mechanoenergetic profile has not been yet established. We made a volume overload (VO) heart failure model in rats and for the first time investigated left ventricular (LV) mechanical work and energetics in cross-circulated whole heart preparations. Laparotomy was performed in 14 Wistar male rats, and abdominal aortic-inferior vena caval shunt was created in seven rats (VO group). Another seven rats underwent a sham operation without functional shunt (Sham group). LV dimensions changes were followed with weekly transthoracic echocardiography. Three months after surgery, we measured LV pressure and volume and myocardial O2 consumption in isolated heart cross circulation. LV internal dimensions in both systolic and diastolic phases were significantly increased in the VO group versus the Sham group ( P < 0.05). LV pressure was markedly decreased in the VO group versus in the Sham group ( P < 0.05). LV end-systolic pressure-volume relation shifted downward, and myocardial O2 consumption related to Ca2+ handling significantly decreased. The contractile response to Ca2+ infusion was attenuated. Nevertheless, the increase in Ca2+ handling-related O2 consumption per unit change in LV contractility in the VO group was significantly higher than that in the Sham group ( P < 0.05). The levels of sarco(endo)plasmic reticulum Ca2+-ATPase 2a protein were reduced in the VO group ( P < 0.01). In conclusion, VO failing rat hearts had a character of marked contractile dysfunction accompanied with less efficient energy utilization in the Ca2+ handling processes. These results suggest that restoring Ca2+ handling in excitation-contraction coupling would improve the contractility of the myocardium after eccentric cardiac remodeling.

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