Abstract 209: Different Reaction To Lactate Between The Atrial And The Ventricular Muscle In Excitation-contraction Coupling

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Daisuke Shimura ◽  
Yoichiro Kusakari ◽  
Nobuhito Goda ◽  
Susumu Minamisawa
Keyword(s):  
Energy Source ◽  
Papillary Muscle ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Physiological Property ◽  
Mouse Heart ◽  
Atrial Myocardium ◽  
Solution Ph ◽  
Peak Tension ◽  
Ec Coupling

Background: The effect of a metabolic change on excitation-contraction (EC) coupling is poorly understood in the atrial myocardium, while the previous studies have mainly focused on EC coupling in the ventricular myocardioum. Although the myocardium mostly uses fatty acid as an energy source, we have reported that metabolic substrate, includes lactate, can be used for energy production and that the metabolomic profile is different between the atria and the ventricles in mouse heart. In addition, it is still under discussion whether lactate can be an energy source for muscles. In the present study, we aimed to investigate the effect of lactate exposure on EC coupling in the atrial and the ventricular myocardium. Methods: We micro-injected aequorin (a Ca2+-sensitive photoprotein) into superficial cells of the left atrium and/or the left ventricular papillary muscle isolated from mice (C57/BL6, 12 - 17 weeks of age), and simultaneously measured intracellular Ca2+ concentration and tension (1 Hz at 36 °C). We added lactate (~10 mM) into HEPES-Tyrode solution (pH was adjusted at 7.4) and observed the changes in the peak tension and the peak Ca2+ concentration. Results and Conclusion: Lactate at a concentration of 10 mM significantly decreased the peak tension (61.7±6.0%; n = 3; P < 0.05.) and the peak Ca2+ concentration (78.8±4.8%; n = 3; P < 0.05.) in the atrial myocardium. Although we observed similar effect of lactate on the ventricular papillary muscle, it was modest compared with the atrial myocardium (72.8±5.6%, 91.6±13.5%, peak tension and Ca2+, respectively; n = 3; no significance). Our results suggest that the atrium has different characteristic of EC coupling from the ventricles in response to an increase in lactate, of which condition is often observed in myocardial ischemia. Moreover, lactate did not seem to contribute to make energy in terms of the tension in the heart. Simultaneous measurement of tension and intracellular Ca2+ concentration can be useful to analyze the atrial physiological property.

Abstract 17185: Sympathetic Reinnervation is Required for Mammalian Cardiac Regeneration

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ian A White ◽  
Julie Gordon ◽  
Wayne Balkan ◽  
Joshua M Hare
Keyword(s):  
Sympathetic Innervation ◽  
Cardiac Regeneration ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Neonatal Mouse ◽  
Left Ventricular Myocardium ◽  
Autonomic Nerves ◽  
Mouse Heart ◽  
Minimal Scarring ◽  
Age Related

Rationale: Established animal models of tissue and limb regeneration demonstrate a critical dependence on concurrent reinnervation by the peripheral nervous system. The abundance of autonomic nerves in the mammalian heart suggests they play a similar role in the response to cardiac injury. Objective: To test the hypothesis that reinnervation is required for innate neonatal cardiac regeneration. Methods and Results: Crossing Wnt1:cre transgenic mice with a double-tandem (td) tomato reporter strain identified all neural crest-derived cell lineages including the peripheral autonomic nerves in the heart. Whole mount epi-fluorescence microscopy facilitated the clear resolution of subepicardial autonomic nerves in the mouse ventricles providing unprecedented detail of the subepicardial neuroanatomy of the mouse heart. We confirmed that sympathetic nerve structures envelop the entire heart, and importantly, exhibit robust re-growth into the regenerating myocardium following resection of the left ventricular apex in neonatal mice. While innervated hearts regenerate with minimal scarring to the left ventricular myocardium, we report that innate cardiac regeneration was inhibited following sympathectomy, as determined by cross-sectional percentage of viable LV myocardium (n=9, 0.87±1.4% vs. n=6, 14.05±4.4% ; p<0.01). Conclusions: Ablation of post-ganglionic sympathetic nerves blocks the innate regenerative capacity of neonatal mouse hearts. Therefore, the innate ability of the neonatal mouse heart to undergo regeneration in response to injury is dependent on sympathetic innervation of the ventricular myocardium. This finding has significant implications for adult regeneration following myocardial infarction where nerve growth is hindered by age related influences and scar tissue.

scholarly journals 1047 Increased interstitial fibrosis in patients with mitral valve prolapse and mitro-annular dysjunction

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A Pavon ◽  
S Hugelshofer ◽  
T Rutz ◽  
P Pascale ◽  
E Pruvot ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Papillary Muscle ◽  
Mitral Valve Prolapse ◽  
Interstitial Fibrosis ◽  
Extracellular Volume ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Control Group ◽  
Left Ventricular Myocardium ◽  
Inferior Wall

Abstract Background in patients with myxomatous mitral valve prolapse (MVP), mitral annular disjunction (MAD) has been associated with the presence of late gadolinium enhancement (LGE) at papillary muscle level and the risk of sudden cardiac death. However, patients with MAD but no detectable LGE still may have arrhythmia. We investigated the relation between MAD and the presence of interstitial fibrosis in the basal inferior left ventricular myocardium. Methods 28 patient with MVP and associated MAD underwent Cardiovascular Magnetic Resonance imaging (CMR) at 1.5 T scanner (Aera, Siemens Medical Solutions, Erlangen, Germany). Exclusion criteria were ischemic heart disease, infiltrative cardiomyopathy and contraindication to CMR. 12 patients with mitral valve regurgitation but no MAD and 10 patients without mitral disease served as the control group. MAD severity was measured from LA wall-posterior MV leaflet junction to the top of the LV infero-basal wall during end systole. Insterstitial fibrosis was assessed by calculating the extracellular volume (ECV) from T1 mapping of the left ventricular basal slice acquired before and after Gadolinium injection. Results Mean age was 47,5+\-23,3 years and 60% were male. ECV was higher in patients with MVP compared with controls (basal septum: 0.27 ± 0.04 vs 0.23 ± 0.03 p = 0.006; basal inferoposterior wall 0.28 ± 0.03 vs 0.23 ± 0.02 p = 0.003) and there was a significant correlation between MAD severity and ECV of the basal inferior wall (spearman rho 0.68, p &lt; 0.0001) (Figure 1). Among MVP patients, ECV of the basal inferoposterior wall was higher in patients positive for LGE in the papillary muscles (ECV 0.31 ± 0.03 vs 0.27 ± 0.03 p 0,004). Conclusion In MVP patients, MAD severity was associated with a higher amount of interstitial fibrosis even in the absence of detectable macroscopic fibrosis in the papillary muscle region. Abstract 1047 Figure 1

scholarly journals Effects of Telmisartan on Myocardial Protein Profiles in Hypertensive Rats

2021 ◽  
Vol 34 (3) ◽  
pp. 299-299
Author(s):  
Yu Feng ◽  
Man-li Zhou ◽  
Jian-zhang Wang ◽  
Jia-qi Zhang ◽  
Shu-le Qian ◽  
...  
Keyword(s):  
Heat Shock ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Sterile Water ◽  
Protein Profiles ◽  
Related Protein ◽  
Hypertensive Rats ◽  
Treatment Groups ◽  
Proteasome 26S

Abstract Background To investigate the effects of telmisartan on the protein profiles of the left ventricular myocardium in spontaneously hypertensive rats (SHR). Methods Sixteen SHR were randomly divided into control and telmisartan treatment groups. Rats were treated with sterile water (10 ml/kg) or telmisartan (4.33 mg/kg) by gavage for 12 weeks. Wistar-Kyoto (WKY) rats treated with sterile water (10 ml/kg) as controls. At the end of 12 weeks of control or telmisartan treatment, rats were sacrificed, and hearts were collected for protein preparations, isotope labeling, and mass spectrometric analysis. Results In total, there were 23 differentially expressed proteins in the left ventricular myocardium between control and telmisartan treatment groups in SHR. Compared with the telmisartan group, the upregulated proteins in the SHR were dual-specificity mitogen-activated protein kinase kinase 3-like, transgelin, and haptoglobin subtype 2. The downregulated proteins in the SHR were as follows: von Willebrand factor (fragment), kininogen 1, small ribonucleoprotein-related protein, fibrinogen beta chain, protein mass 3 (fragment), proteasome 26s, heat shock protein 27-related protein 1, tenascin X, fibronectin subtype 2, transferrin receptor protein, platelets 1, cathepsin L1, complement factor B, isoform CRA_b, fibrinogen isomer, immunoglobulin heavy chain (γ polypeptide), and α 1 antiprotease. Conclusions Telmisartan differentially regulates myocardial protein expression in hypertensive rats including heat shock protein 27, fibrinogen, fibronectin, proteasome 26s and transgelin, as well as proteins in biochemical, metabolic, and signal transduction pathways. These changes in protein expression may contribute to the antihypertrophic effects of telmisartan in hypertension.

scholarly journals Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yankun Lyu ◽  
Vipin K. Verma ◽  
Younjee Lee ◽  
Iosif Taleb ◽  
Rachit Badolia ◽  
...  
Keyword(s):  
Heart Function ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Excitation Contraction Coupling ◽  
Transverse Tubular System ◽  
Contraction Coupling ◽  
Senescent Phenotype ◽  
Cellular Microstructure ◽  
T System

AbstractIt is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF. Using left ventricular myocardium from donors and HF patients with ages between 19 and 75 years, we established a library of 3D reconstructions of the t-system as well as ryanodine receptor (RyR) and junctophilin 2 (JPH2) clusters. Aging was characterized by t-system alterations and sarcolemmal dissociation of RyR clusters. This remodeling was less pronounced than in HF and accompanied by major alterations of JPH2 arrangement. Our study indicates that targeting sarcolemmal association of JPH2 might ameliorate age-associated deficiencies of heart function.

scholarly journals Myxomatous Mitral Valve Disease with Mitral Valve Prolapse and Mitral Annular Disjunction: Clinical and Functional Significance of the Coincidence

2021 ◽  
Vol 8 (2) ◽  
pp. 9
Author(s):  
Nina C. Wunderlich ◽  
Siew Yen Ho ◽  
Nir Flint ◽  
Robert J. Siegel
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Disease ◽  
Morphological Changes ◽  
Morphological Characteristics ◽  
Mitral Annulus ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Valve Disease ◽  
Left Ventricular Myocardium ◽  
Basal Portion

The morphological changes that occur in myxomatous mitral valve disease (MMVD) involve various components, ultimately leading to the impairment of mitral valve (MV) function. In this context, intrinsic mitral annular abnormalities are increasingly recognized, such as a mitral annular disjunction (MAD), a specific anatomical abnormality whereby there is a distinct separation between the mitral annulus and the left atrial wall and the basal portion of the posterolateral left ventricular myocardium. In recent years, several studies have suggested that MAD contributes to myxomatous degeneration of the mitral leaflets, and there is growing evidence that MAD is associated with ventricular arrhythmias and sudden cardiac death. In this review, the morphological characteristics of MAD and imaging tools for diagnosis will be described, and the clinical and functional aspects of the coincidence of MAD and myxomatous MVP will be discussed.

scholarly journals DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism

2020 ◽  
Vol 36 (1) ◽  
pp. 136-146
Author(s):  
Nozomi Furukawa ◽  
Norimichi Koitabashi ◽  
Hiroki Matsui ◽  
Hiroaki Sunaga ◽  
Yogi Umbarawan ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Systolic Function ◽  
Cardiac Fibroblasts ◽  
Left Ventricular ◽  
Sirtuin 1 ◽  
Fibroblast Growth Factor 21 ◽  
Mouse Heart ◽  
Acid Uptake ◽  
Dipeptidyl Peptidase 4 ◽  
Fgf21 Expression

AbstractDipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin (vilda), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or vilda, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in vilda-treated mice. Pressure–volume analysis showed that vilda treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that vilda treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by vilda treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with vilda treatment. Vilda treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert vilda-mediated beneficial effects in stressed heart. Vilda induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

scholarly journals Heart transplantation in an adult patient with isolated noncompaction of the left ventricular myocardium

Medicina ◽  
2010 ◽  
Vol 46 (3) ◽  
pp. 193 ◽  
Author(s):  
Sigita Glaveckaitė ◽  
Kęstutis Ručinskas ◽  
Jelena Čelutkienė ◽  
Vytė Maneikienė ◽  
Diana Zakarkaitė ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Adult Patient ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Important Process ◽  
Ventricular Noncompaction ◽  
Myocardial Development ◽  
Myocardial Fibers ◽  
Heart Lesions

Isolated noncompaction of the ventricular myocardium is defined as a rare cardiomyopathy caused by intrauterine arrest of compaction of the myocardial fibers and meshwork, an important process in myocardial development, in absence of any coexisting congenital heart lesions. A lot of controversies exist about diagnostic criteria, nomenclature, origin, pathogenesis, and prognosis of this disease. Here, we describe an adult patient with isolated left ventricular noncompaction who presented with worsening congestive heart failure and was successfully treated with heart transplantation.

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