Adult zebrafish ventricular electrical gradients as tissue mechanisms of ECG patterns under baseline vs. oxidative stress.

Abstract:

AIMS:In mammalian ventricles, electrical gradients establish electrical heterogeneities as essential tissue mechanisms to optimize mechanical efficiency and safeguard electrical stability. Electrical gradients shape mammalian electrocardiographic patterns; disturbance of electrical gradients is proarrhythmic. The zebrafish heart is a popular surrogate model for human cardiac electrophysiology thanks to its remarkable recapitulation of human electrocardiogram and ventricular action potential features. Yet, zebrafish ventricular electrical gradients are largely unexplored. The goal of this study is to define the zebrafish ventricular electrical gradients that shape the QRS complex and T wave patterns at baseline and under oxidative stress. METHODS AND RESULTS:We performed in vivo electrocardiography and ex vivo voltage-sensitive fluorescent epicardial and transmural optical mapping of adult zebrafish hearts at baseline and during acute H2O2 exposure. At baseline, apicobasal activation and basoapical repolarization gradients accounted for the polarity concordance between the QRS complex and T wave. During H2O2 exposure, differential regional impairment of activation and repolarization at the apex and base disrupted prior baseline electrical gradients, resulting in either reversal or loss of polarity concordance between the QRS complex and T wave. KN-93, a specific calcium/calmodulin-dependent protein kinase II inhibitor (CaMKII), protected zebrafish hearts from H2O2 disruption of electrical gradients. The protection was complete if administered prior to oxidative stress. CONCLUSIONS:Despite remarkable apparent similarities, zebrafish and human ventricular electrocardiographic patterns are mirror images supported by opposite electrical gradients. Like mammalian ventricles, zebrafish ventricles are also susceptible to H2O2 proarrhythmic perturbation via CaMKII activation. Our findings suggest that the adult zebrafish heart may constitute a clinically relevant model to investigate ventricular arrhythmias induced by oxidative stress. However, the fundamental ventricular activation and repolarization differences between the two species that we demonstrated in this study highlight the potential limitations when extrapolating results from zebrafish experiments to human cardiac electrophysiology, arrhythmias, and drug toxicities. TRANSLATIONAL PERSPECTIVE:Zebrafish electrocardiograms remarkably recapitulate human electrocardiograms in health and disease. Yet, the underlying tissue mechanisms were unknown. This study provides the first demonstration that the baseline electrical gradients that shape zebrafish ventricular electrocardiograms are opposite human electrical gradients. Additionally, like mammalian hearts, zebrafish hearts are susceptible to CaMKII-mediated H2O2 proarrhythmic perturbations. Despite its vital role in zebrafish cardiac regeneration following injury, H2O2 can disrupt zebrafish sinus node activity, cause all three types of atrioventricular blocks, and reverse ventricular electrical gradients. These findings highlight the clinical relevance, utility, and limitations of the adult zebrafish heart as model for mammalian arrhythmogenesis studies.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Zhao Y,James NA,Beshay AR,Chang EE,Lin A,Bashar F,Wassily A,Nguyen B,Nguyen TP

doi

10.1093/cvr/cvaa238

subject

Has Abstract

pub_date

2020-07-31 00:00:00

eissn

0008-6363

issn

1755-3245

pii

5879279

pub_type

杂志文章
  • Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture by a survival pathway targeting SR Ca2+ storage.

    abstract:OBJECTIVE:Experimental and clinical studies have shown that administration of insulin during reperfusion is cardioprotective, but the underlying mechanisms are still unknown. In this study, we investigated in isolated rat cardiomyocytes subjected to hypoxia and reoxygenation whether administration of insulin during reo...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2006.02.020

    authors: Abdallah Y,Gkatzoflia A,Gligorievski D,Kasseckert S,Euler G,Schlüter KD,Schäfer M,Piper HM,Schäfer C

    更新日期:2006-05-01 00:00:00

  • Targeted invalidation of SR-B1 in macrophages reduces macrophage apoptosis and accelerates atherosclerosis.

    abstract:AIMS:SR-B1 is a cholesterol transporter that exerts anti-atherogenic properties in liver and peripheral tissues in mice. Bone marrow (BM) transfer studies suggested an atheroprotective role in cells of haematopoietic origin. Here, we addressed the specific contribution of SR-B1 in the monocyte/macrophage. METHODS AND ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvz138

    authors: Galle-Treger L,Moreau M,Ballaire R,Poupel L,Huby T,Sasso E,Troise F,Poti F,Lesnik P,Le Goff W,Gautier EL,Huby T

    更新日期:2020-03-01 00:00:00

  • Transient down-regulation of L-type Ca(2+) channel and dystrophin expression after balloon injury in rat aortic cells.

    abstract:OBJECTIVE:Migration and proliferation of arterial smooth muscle cells are critical responses during restenosis after balloon angioplasty. We investigated the changes in the expression of Ca(2+) channels and dystrophin, two determinants of contraction, after balloon injury of rat aortas. METHODS:Proliferation and migra...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00210-8

    authors: Quignard JF,Harricane MC,Ménard C,Lory P,Nargeot J,Capron L,Mornet D,Richard S

    更新日期:2001-01-01 00:00:00

  • Post-extrasystolic left ventricular peak pressure with and without left ventricular failure.

    abstract::18 patients without valvular pathology, coronary artery disease, or idiopathic hypertrophic subaortic stenosis were haemodynamically and angiographically investigated in order to analyse the effects of a ventricular extrasystolic beat upon the post-extrasystolic left ventricular peak pressure. In eight normal patients...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/13.6.338

    authors: Merillon JP,Motte G,Aumont MC,Masquet C,Lecarpentier Y,Gourgon R

    更新日期:1979-06-01 00:00:00

  • MicroRNA-195 promotes palmitate-induced apoptosis in cardiomyocytes by down-regulating Sirt1.

    abstract:AIMS:Free fatty acids induce apoptosis in cardiomyocytes, which is implicated in lipotoxic cardiomyopathy. However, the underlying mechanisms remain not fully understood. MicroRNAs (miRNAs) are non-coding small RNAs that control gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to b...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvr145

    authors: Zhu H,Yang Y,Wang Y,Li J,Schiller PW,Peng T

    更新日期:2011-10-01 00:00:00

  • The influence of coronary collateral flow on the assessment of myocardial perfusion by videodensitometry.

    abstract:OBJECTIVES:Coronary collateral flow often mitigates the effects of coronary artery obstruction and has a significant impact on the prognosis of patients with coronary artery disease. In the presence of variable degrees of coronary collateral flow, digital radiographic assessment of myocardial blood flow has not been qu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(96)00218-0

    authors: Murata K,Bhargava V,Ricou F,Ono S,Kambayashi M,Oh BH,Peterson KL

    更新日期:1997-02-01 00:00:00

  • Effect of acute cardiac tamponade on left ventricular pressure-volume relations in anaesthetised dogs.

    abstract:STUDY OBJECTIVE:The aim was to determine whether depressed myocardial contractility is responsible for the decline in stroke volume that occurs with cardiac tamponade. DESIGN:Left ventricular contractile performance was assessed before and after beta adrenergic blockade using the end systolic pressure-volume relation,...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/24.8.633

    authors: Johnston WE,Vinten-Johansen J,Klopfenstein HS,Santamore WP,Little WC

    更新日期:1990-08-01 00:00:00

  • High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation.

    abstract:AIMS:Diabetes is a major risk factor for cardiovascular diseases. Circulating endothelial microparticles (EMP) are increased in diabetic patients, but their potential contribution in atherogenesis is unclear. We sought to determine the role of EMP derived under high glucose conditions in the development of atherosclero...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvt013

    authors: Jansen F,Yang X,Franklin BS,Hoelscher M,Schmitz T,Bedorf J,Nickenig G,Werner N

    更新日期:2013-04-01 00:00:00

  • Previous-beat contraction history is not influenced by mechanosensitive ion channel blockade.

    abstract:OBJECTIVES:Prior studies have shown that the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, a phenomenon called "previous-beat contraction history". This previous-beat contraction history, which appears to be an interplay between the mechanical events of o...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Slinker BK,Tobias AH

    更新日期:1996-07-01 00:00:00

  • Abnormal neurovascular coupling as a cause of excess cerebral vasodilation in familial migraine.

    abstract:AIMS:Acute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na, K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R mice) were shown to have elevated cerebrovascular tone ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvz306

    authors: Staehr C,Rajanathan R,Postnov DD,Hangaard L,Bouzinova EV,Lykke-Hartmann K,Bach FW,Sandow SL,Aalkjaer C,Matchkov VV

    更新日期:2020-10-01 00:00:00

  • C-reactive protein in atherosclerosis: A causal factor?

    abstract::Atherosclerosis is considered a to be multifactorial disease driven by inflammatory reactions. The process of inflammation also contributes to the pathogenesis of acute atherothrombotic events. C-reactive protein (CRP) is an acute phase protein and its concentration in serum reflects the inflammatory condition of the ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/j.cardiores.2006.03.004

    authors: Paffen E,DeMaat MP

    更新日期:2006-07-01 00:00:00

  • Differential role of platelet granular mediators in angiogenesis.

    abstract:OBJECTIVES:Platelets contain numerous substances regulating angiogenic response. However, the regulatory role of platelets in blood vessel development remains to be elucidated. We investigated the comprehensive effect of platelets as a cellular system on angiogenesis. METHODS:The following approaches were applied: (a)...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2004.04.012

    authors: Brill A,Elinav H,Varon D

    更新日期:2004-08-01 00:00:00

  • Effect of circulation time on plasma high density lipoprotein cholesterol in rats.

    abstract::The effect of circulation time on plasma high density lipoprotein cholesterol concentrations was investigated in 20 male Wistar rats injected with alcohol, stressed with lighting, or fed a high fat diet. Circulation time was measured during anaesthesia with a computerised dichromatic earpiece densitometer. Indocyanine...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/22.5.368

    authors: Ishizuka T

    更新日期:1988-05-01 00:00:00

  • Pitx2 impairs calcium handling in a dose-dependent manner by modulating Wnt signalling.

    abstract:AIMS:Atrial fibrillation (AF) is the most common type of arrhythmia in humans, yet the genetic cause of AF remains elusive. Genome-wide association studies (GWASs) have reported risk variants in four distinct genetic loci, and more recently, a meta-GWAS has further implicated six new loci in AF. However, the functional...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvv207

    authors: Lozano-Velasco E,Hernández-Torres F,Daimi H,Serra SA,Herraiz A,Hove-Madsen L,Aránega A,Franco D

    更新日期:2016-01-01 00:00:00

  • Inhibition of adrenergic neurotransmission in ischaemic regions of the canine left ventricle.

    abstract::To test hypothesis that adrenergic neurotransmission is impaired in acute myocardial ischaemia, we studied contractile function of normal and ischaemic myocardium after coronary artery occlusion. For each area we compared the contractile response to left sympathetic nerve stimulation (LSS) with the response to exogeno...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/14.2.116

    authors: Martins JB,Kerber RE,Marcus ML,Laughlin DL,Levy DM

    更新日期:1980-02-01 00:00:00

  • GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy.

    abstract:AIMS:GATA4 is a transcription factor that is up-regulated during cardiac hypertrophy and plays a fundamental role in myocyte growth and survival. In this study, we investigate the transcriptional vs. post-transcriptional mechanisms that are involved in regulating GATA4 in the heart during neonatal and pressure overload...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvs001

    authors: Han M,Yang Z,Sayed D,He M,Gao S,Lin L,Yoon S,Abdellatif M

    更新日期:2012-03-15 00:00:00

  • Expression of homocellular and heterocellular gap junctions in hamster arterioles and feed arteries.

    abstract:OBJECTIVES:Conduction of vasoconstrictor and vasodilator responses in the microcirculation involves electrical coupling through gap junction channels among cells of the vascular wall. The present study determined whether reported differences in the properties of conduction along the arterioles of the epithelial hamster...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2003.09.017

    authors: Sandow SL,Looft-Wilson R,Doran B,Grayson TH,Segal SS,Hill CE

    更新日期:2003-12-01 00:00:00

  • S100A4 is upregulated in injured myocardium and promotes growth and survival of cardiac myocytes.

    abstract:OBJECTIVE:The multifunctional Ca2+-binding protein S100A4 (also known as Mts1 and Fsp1) is involved in fibrosis and tissue remodeling in several diseases including cancer, kidney fibrosis, central nervous system injury, and pulmonary vascular disease. We previously reported that S100A4 mRNA expression was increased in ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2007.03.027

    authors: Schneider M,Kostin S,Strøm CC,Aplin M,Lyngbaek S,Theilade J,Grigorian M,Andersen CB,Lukanidin E,Lerche Hansen J,Sheikh SP

    更新日期:2007-07-01 00:00:00

  • Adaptive mechanisms of the aorta and left ventricle to volume overloading following abrupt aortic regurgitation in rabbits.

    abstract:STUDY OBJECTIVE:Compensatory mechanisms of the left ventricle for volume overloading caused by acute aortic regurgitation and associated changes in physiological properties of the aorta were studied in rabbits. DESIGN:Aortic regurgitation was produced by aortic valve perforation, and haemodynamic measurements were per...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/25.6.463

    authors: Wainai Y

    更新日期:1991-06-01 00:00:00

  • STAT3, a key regulator of cell-to-cell communication in the heart.

    abstract::The signal transducer and activator of transcription 3 (STAT3) is fundamental for physiological homeostasis and stress-induced remodelling of the heart as deregulated STAT3 circuits are sufficient to induce dilated and peripartum cardiomyopathy and adverse remodelling after myocardial infarction. STAT3 activity depend...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvu034

    authors: Haghikia A,Ricke-Hoch M,Stapel B,Gorst I,Hilfiker-Kleiner D

    更新日期:2014-05-01 00:00:00

  • Comparative DNA methylation and gene expression analysis identifies novel genes for structural congenital heart diseases.

    abstract:AIMS:For the majority of congenital heart diseases (CHDs), the full complexity of the causative molecular network, which is driven by genetic, epigenetic, and environmental factors, is yet to be elucidated. Epigenetic alterations are suggested to play a pivotal role in modulating the phenotypic expression of CHDs and t...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvw195

    authors: Grunert M,Dorn C,Cui H,Dunkel I,Schulz K,Schoenhals S,Sun W,Berger F,Chen W,Sperling SR

    更新日期:2016-10-01 00:00:00

  • The class III antiarrhythmic drugs dofetilide and sotalol prevent AF induction by atrial premature complexes at doses that fail to terminate AF.

    abstract:BACKGROUND:Clinical trials suggest that sotalol and dofetilide are much more effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of discordant sotalol and dofetilide effects on AF termination vs. prevention. METHODS:We applied 240-electrode epicardial mapp...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00320-5

    authors: Derakhchan K,Villemaire C,Talajic M,Nattel S

    更新日期:2001-04-01 00:00:00

  • Angiotensin converting enzyme and kininase-II-like activities in cultured valvular interstitial cells of the rat heart.

    abstract:OBJECTIVE:The function of angiotensin converting enzyme (ACE) at cell sites of high collagen turnover, such as heart valves, is uncertain. The aim of this study was to assess ACE and kininase-II-like activities and collagen turnover in cultured valvular interstitial cells of the adult rat heart. METHODS:The valvular i...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Katwa LC,Ratajska A,Cleutjens JP,Sun Y,Zhou G,Lee SJ,Weber KT

    更新日期:1995-01-01 00:00:00

  • A gene therapeutic approach to inhibit calcium and integrin binding protein 1 ameliorates maladaptive remodelling in pressure overload.

    abstract:Aims:Chronic heart failure is becoming increasingly prevalent and is still associated with a high mortality rate. Myocardial hypertrophy and fibrosis drive cardiac remodelling and heart failure, but they are not sufficiently inhibited by current treatment strategies. Furthermore, despite increasing knowledge on cardiom...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvy154

    authors: Grund A,Szaroszyk M,Döppner JK,Malek Mohammadi M,Kattih B,Korf-Klingebiel M,Gigina A,Scherr M,Kensah G,Jara-Avaca M,Gruh I,Martin U,Wollert KC,Gohla A,Katus HA,Müller OJ,Bauersachs J,Heineke J

    更新日期:2019-01-01 00:00:00

  • Prevention of ischemic rigor contracture during coronary occlusion by inhibition of Na(+)-H+ exchange.

    abstract:OBJECTIVE:To determine the effect of Na(+)-H+ exchange blockade on ischemic rigor contracture and reperfusion-induced hypercontracture. METHODS:Thirty-six pigs were submitted to 55 min of coronary occlusion and 5 h reperfusion. Myocardial segment length analysis with ultrasonic microcrystals was used to detect ischemi...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(97)00106-5

    authors: Garcia-Dorado D,González MA,Barrabés JA,Ruiz-Meana M,Solares J,Lidon RM,Blanco J,Puigfel Y,Piper HM,Soler-Soler J

    更新日期:1997-07-01 00:00:00

  • Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice.

    abstract:AIMS:Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investi...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp043

    authors: Liu SL,Li YH,Shi GY,Tang SH,Jiang SJ,Huang CW,Liu PY,Hong JS,Wu HL

    更新日期:2009-04-01 00:00:00

  • RhoA activation and interaction with Caveolin-1 are critical for pressure-induced myogenic tone in rat mesenteric resistance arteries.

    abstract:OBJECTIVE:Myogenic tone, which has a major role in the regulation of local blood flow, refers to the ability of vascular smooth muscle to adapt its contractility to changes in transmural pressure. Although Rho-kinase is involved in myogenic tone, the pathway involved remains unclear, especially concerning translocation...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2006.10.020

    authors: Dubroca C,Loyer X,Retailleau K,Loirand G,Pacaud P,Feron O,Balligand JL,Lévy BI,Heymes C,Henrion D

    更新日期:2007-01-01 00:00:00

  • Identification and immunolocalisation of annexins V and VI, the major cardiac annexins, in rat heart.

    abstract:OBJECTIVE:The heart contains proteins of the annexin family, a unique group of calcium binding proteins. This study was aimed at identifying the major cardiac annexins and determining their distribution in the rat heart. METHODS:Annexins were isolated by affinity chromatography and purified by ion exchange high pressu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/27.7.1359

    authors: Doubell AF,Lazure C,Charbonneau C,Thibault G

    更新日期:1993-07-01 00:00:00

  • Short-term delivery of anti-PlGF antibody delays progression of atherosclerotic plaques to vulnerable lesions.

    abstract:AIMS:Placental growth factor (PlGF), a homologue of vascular endothelial growth factor, is a pleiotropic cytokine with a pro-inflammatory activity. Previous gene-inactivation studies revealed that the loss of PlGF delays atherosclerotic lesion development and inhibits macrophage infiltration, but the activity of an ant...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp380

    authors: Roncal C,Buysschaert I,Gerdes N,Georgiadou M,Ovchinnikova O,Fischer C,Stassen JM,Moons L,Collen D,De Bock K,Hansson GK,Carmeliet P

    更新日期:2010-04-01 00:00:00

  • Effects of regional ischaemia, with or without reperfusion, on endothelium dependent coronary relaxation in the dog.

    abstract:OBJECTIVE:The aim was to establish whether the duration of coronary ischaemia and coronary ischaemia with reperfusion selectively reduced the magnitude of relaxation mediated by endothelium dependent relaxing factor (EDRF) in response to thrombin, compared with relaxation produced by acetylcholine and calcimycin. METH...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/26.3.250

    authors: Winn MJ,Ku DD

    更新日期:1992-03-01 00:00:00