Leif Hove‐Madsen

ORCID: 0000-0001-5493-3998
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About
Contact & Profiles
Research Areas
  • Cardiac electrophysiology and arrhythmias
  • Ion channel regulation and function
  • Neuroscience and Neural Engineering
  • Atrial Fibrillation Management and Outcomes
  • Cardiac Arrhythmias and Treatments
  • Cardiomyopathy and Myosin Studies
  • Cardiac pacing and defibrillation studies
  • Physiological and biochemical adaptations
  • Cardiovascular Effects of Exercise
  • Receptor Mechanisms and Signaling
  • Neuroscience and Neuropharmacology Research
  • Phosphodiesterase function and regulation
  • Mitochondrial Function and Pathology
  • Congenital heart defects research
  • RNA Research and Splicing
  • Corrosion Behavior and Inhibition
  • Neurobiology and Insect Physiology Research
  • Mesenchymal stem cell research
  • Hydrogen embrittlement and corrosion behaviors in metals
  • Cardiovascular Function and Risk Factors
  • Pluripotent Stem Cells Research
  • Adenosine and Purinergic Signaling
  • Zebrafish Biomedical Research Applications
  • Tissue Engineering and Regenerative Medicine
  • Nuclear Receptors and Signaling

Hospital de Sant Pau
2016-2025

Centro de Investigación en Red en Enfermedades Cardiovasculares
2010-2025

Centre for Biomedical Network Research on Rare Diseases
2024-2025

Institut d'Investigacions Biomèdiques de Barcelona
2018-2024

Centro de Investigación Biomédica en Red
2020-2024

Institut de Recerca Sant Pau
2023-2024

Consejo Superior de Investigaciones Científicas
2010-2023

Instituto de Salud Carlos III
2020-2023

Complejo Hospitalario de Jaén
2021

Simon Fraser University
2011-2019

Background— Pitx2 is a homeobox transcription factor that plays pivotal role in early left/right determination during embryonic development. loss-of-function mouse mutants display lethality with severe cardiac malformations, demonstrating the importance of cardiogenesis. Recently, independent genome-wide association studies have provided new evidence for putative PITX2 adult heart. These independently reported several risk variants close to locus on chromosome 4q25 are strongly associated...

10.1161/circgenetics.110.958116 article EN Circulation Cardiovascular Genetics 2011-04-22

Abstract Aims Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated risk AF-related complications. The aim this document to summarize key outcomes 9th AFNET/EHRA Consensus Conference Atrial Fibrillation NETwork (AFNET) European Heart Rhythm Association (EHRA). Methods results Eighty-three international experts met Münster for 2 days September 2023. Key findings...

10.1093/europace/euae070 article EN cc-by-nc EP Europace 2024-03-22

Background— Spontaneous Ca 2+ release from the sarcoplasmic reticulum (SR) can generate afterdepolarizations, and these have potential to initiate arrhythmias. Therefore, an association may exist between spontaneous SR initiation of atrial fibrillation (AF), but this has not yet been reported. Methods Results— SR, manifested as sparks waves, was recorded with confocal microscopy in myocytes isolated patients those without AF. In addition, inward current associated waves measured use...

10.1161/01.cir.0000141296.59876.87 article EN Circulation 2004-08-17

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases that often co-exist. Animal models have suggested complex AF-promoting atrial structural, electrical, Ca2+-handling remodeling in the setting of HF, but data human samples scarce, particularly regarding remodeling. Here, we evaluated patients with severe left ventricular (LV) dysfunction (HFrEF), long-standing persistent ('chronic') AF (cAF) or both (HFrEF-cAF), sinus rhythm controls normal LV function (Ctl)...

10.3389/fphys.2018.01383 article EN cc-by Frontiers in Physiology 2018-10-09

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia, a condition characterized by prominent ectopy in response to catecholamine stress, which can be reproduced on exercise stress testing (EST). However, reports of sudden cardiac death (SCD) have emerged EST-negative individuals who loss-of-function (LOF) RyR2 mutations. The clinical relevance LOF including their pathogenic mechanism, diagnosis, and treatment are all...

10.1126/scitranslmed.aba7287 article EN Science Translational Medicine 2021-02-03

Passive Ca binding was measured with a Ca-selective minielectrode in suspensions of permeabilized rabbit ventricular myocytes equilibrated 5 microM thapsigargin and 30 ruthenium red to prevent sarcoplasmic reticulum (SR) or mitochondrial uptake. obtained by titration the subtraction blank without myocytes. could be described Michaelis curve two sites: K1 = 0.42 n1 1.27 nmol/mg cell protein K2 79 microM, n2 4.13 protein. The passive buffering over physiological concentration approximately...

10.1152/ajpcell.1993.264.3.c677 article EN AJP Cell Physiology 1993-03-01

Ca2+ uptake by the sarcoplasmic reticulum (SR) and free [Ca2+] were measured simultaneously with indo 1 a Ca(2+)-selective minielectrode in suspensions of permeabilized rabbit or rat ventricular myocytes (approximately 10 mg/mL protein). In presence 25 mumol/L ruthenium red mmol/L oxalate, Km for SR was approximately 250 nmol/L myocytes. The maximal rate 2.4 times higher than rabbit. Addition 5 nmol thapsigargin (TG) per milligram cell protein abolished completely both species. [TG]...

10.1161/01.res.73.5.820 article EN Circulation Research 1993-11-01

Atrial fibrillation (AF) is the most common type of arrhythmia in humans, yet genetic cause AF remains elusive. Genome-wide association studies (GWASs) have reported risk variants four distinct loci, and more recently, a meta-GWAS has further implicated six new loci AF. However, functional role these GWAS-related genes their inter-relationship remain To get insights into molecular mechanisms driven by Pitx2, calcium handling novel GWAS-associated gene expression were analysed two Pitx2...

10.1093/cvr/cvv207 article EN Cardiovascular Research 2015-08-04

Ageing-related cardiac disorders such as heart failure and atrial fibrillation often present with intracellular calcium homeostasis dysfunction. However, knowledge of the intrinsic effects ageing on cellular handling in human is sparse. Therefore, this study aimed to analyse how affects key mechanisms that regulate myocytes. Whole membrane currents transients were measured isolated right myocytes from 80 patients normal left dimensions no history fibrillation. Patients categorized young (<55...

10.1093/cvr/cvv046 article EN cc-by-nc Cardiovascular Research 2015-02-24

The relationship between stimulation frequency and contraction was established for ventricular strips from rainbow trout heart at 5, 15 25 degrees C. Compared to mammalian species, changes in temperature had little impact on force development ventricle physiologically relevant frequencies. However, the force-frequency changed a biphasic response with minimum around 0.2 Hz 5 C monophasic decline increasing Ryanodine reversed negative Potentiation of twitch after min rest period increased 121...

10.1242/jeb.167.1.47 article EN Journal of Experimental Biology 1992-06-01

Atrial fibrillation (AF) is associated with abnormal sarcoplasmic reticulum (SR) calcium release, which promoted by adenosine A2A receptor (A2AR) activation. Here, we tested the hypothesis that release in AF linked to A2AR remodelling. Western blotting and quantitative real-time PCR were used determine mRNA protein levels right atrial samples from patients without AF. Effects of activation on handling assessed patch-clamp technique confocal imaging. functional A2ARs moderately up-regulated...

10.1093/eurheartj/ehq464 article EN European Heart Journal 2010-12-22

Phospholamban (PLN) is an inhibitor of cardiac sarco(endo)plasmic reticulum Ca²⁺ ATPase. PLN knockout (PLN-KO) enhances sarcoplasmic load and leak. Conversely, PLN-KO accelerates sequestration aborts arrhythmogenic spontaneous waves (SCWs). An important question whether these seemingly paradoxical effects exacerbate or protect against Ca²⁺-triggered arrhythmias.We investigate the impact on SCWs, triggered activities, stress-induced ventricular tachyarrhythmias (VTs) in a mouse model...

10.1161/circresaha.113.301678 article EN Circulation Research 2013-07-16

The myocardium accumulates intracellular lipids under ischaemic conditions, and myocardial fat deposition is closely associated with cardiac dysfunction. Our aims were to analyse the effect of hypoxia on low-density lipoprotein receptor-related protein 1 (LRP1) expression in neonatal rat ventricular myocytes (NRVM) cardiac-derived HL-1 cells molecular mechanisms involved this effect, determine role LRP1 very low density (VLDL) uptake by hypoxic cardiomyocytes, study receptor lipid profile an...

10.1093/cvr/cvs136 article EN Cardiovascular Research 2012-03-27

Significance Defective prelamin A processing causes cardiovascular alterations and premature death in Hutchinson–Gilford progeria syndrome (HGPS) patients also occurs during physiological aging. We found overt repolarization abnormalities HGPS at advanced disease stages. Similar were present progeroid Zmpste24 −/− mice, which had cardiomyocytes that exhibited prolonged calcium transient duration reduced sarcoplasmic reticulum loading capacity release, consistent with absence of...

10.1073/pnas.1603754113 article EN Proceedings of the National Academy of Sciences 2016-10-31

Active teleosts such as the salmonids must vary cardiac output severalfold over a wide range of temperatures. Myocardial contractility, an important determinant output, be maintained and regulated in these species under conditions that are cardioplegic to mammals. Contractility is determined primarily by magnitude rate calcium delivery myofilaments. In mammals, relatively small Ca 2+ influx across sarcolemma (SL) triggers release larger pool from sarcoplasmic reticulum (SR). other lower...

10.1139/z91-281 article EN Canadian Journal of Zoology 1991-07-01

Alterations in the cyclic AMP-dependent regulation of cardiac ryanodine receptor (RyR2) have been proposed to account for increased spontaneous calcium release from sarcoplasmic reticulum (SR) patients with heart failure, ventricular tachyarrhythmias and atrial fibrillation. While adenosine A(2A) (A(2A)R) is known regulate AMP levels, expression function this human myocytes has not investigated.PCR, western blotting immunofluorescence were used identify A(2A)R, functional effects A(2A)R...

10.1016/j.cardiores.2006.07.020 article EN Cardiovascular Research 2006-08-01

The zebrafish is an important model for the study of vertebrate cardiac development with a rich array genetic mutations and biological reagents functional interrogation. similarity (Danio rerio) action potential that humans further enhances relevance this model. In spite this, little known about excitation-contraction coupling in heart. To address issue, adult cardiomyocytes were isolated by enzymatic perfusion cannulated ventricle subjected to amphotericin-perforated patch-clamp technique,...

10.1152/ajpregu.00377.2010 article EN AJP Regulatory Integrative and Comparative Physiology 2010-10-07

Irregularities in intracellular calcium on a beat-to-beat basis can precede cardiac arrhythmia, but the mechanisms inducing such irregularities remain elusive. This study tested hypothesis that sarcoplasmic reticulum (SR) and L-type channel activity determine response its rate dependency. For this purpose, patch-clamp technique confocal imaging was used to record current (ICa) visualize human atrial myocytes subjected increasing stimulation frequencies (from 0.2 2 Hz). The heterogeneous...

10.1113/jphysiol.2010.197715 article EN The Journal of Physiology 2011-04-27
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