A5007064175- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Atrial Fibrillation Management and Outcomes
- Cardiovascular Effects of Exercise
- Cardiac Arrhythmias and Treatments
- Cardiomyopathy and Myosin Studies
- Cardiac pacing and defibrillation studies
- Viral Infections and Immunology Research
- Neuroscience and Neural Engineering
- Heat shock proteins research
- Tissue Engineering and Regenerative Medicine
- Receptor Mechanisms and Signaling
- Cardiac Ischemia and Reperfusion
- Cardiac Fibrosis and Remodeling
- 3D Printing in Biomedical Research
- Obstructive Sleep Apnea Research
- Signaling Pathways in Disease
- RNA regulation and disease
- Mechanical Circulatory Support Devices
- Endoplasmic Reticulum Stress and Disease
- Cardiovascular Disease and Adiposity
- Electrospun Nanofibers in Biomedical Applications
- Heparin-Induced Thrombocytopenia and Thrombosis
- Monoclonal and Polyclonal Antibodies Research
- Drug Transport and Resistance Mechanisms
University of Bern
2016-2025
Czech Academy of Sciences, Institute of Physiology
2023
Montreal Heart Institute
2007-2020
Université de Montréal
2006-2015
McGill University
2008-2015
Electrophysiology and Heart Modeling Institute
2014
Institut de Mathématiques de Bordeaux
2014
Nagoya University
2012
Heidelberg University
2011-2012
University Hospital Heidelberg
2011-2012
Atrial fibrillation (AF) is a highly prevalent arrhythmia with pronounced morbidity and mortality. Inward-rectifier K+ current (IK1) believed to be an important regulator of reentrant-spiral dynamics major component AF-related electrical remodeling. MicroRNA-26 (miR-26) predicted target the gene encoding KIR2.1, KCNJ2. We found that miR-26 was downregulated in atrial samples from AF animals patients this downregulation accompanied by upregulation IK1/KIR2.1 protein. overexpression suppressed...
Fibroblast proliferation and differentiation are central in atrial fibrillation (AF)-promoting remodeling. Here, we investigated fibroblast regulation by Ca(2+)-permeable transient receptor potential canonical-3 (TRPC3) channels.Freshly isolated rat cardiac fibroblasts abundantly expressed TRPC3 had appreciable nonselective cation currents (I(NSC)) sensitive to a selective TPRC3 channel blocker, pyrazole-3 (3 μmol/L). Pyrazole-3 suppressed angiotensin II-induced Ca(2+) influx, proliferation,...
Background— Adenosine acutely reconnects pulmonary veins (PVs) after radiofrequency application, revealing “dormant conduction” and identifying PVs at risk of reconnection, but the underlying mechanisms are unknown. Methods Results— Canine PV left-atrial (LA) action potentials were recorded with standard microelectrodes ionic currents whole-cell patch clamp before adenosine perfusion. isolated current application in coronary-perfused LA-PV preparations. abbreviated potential duration...
Atrial tachycardia (AT) downregulates L-type Ca(2+) current (I(CaL)) and causes atrial fibrillation-promoting electric remodeling. This study assessed potential underlying signal transduction. Cultured adult canine cardiomyocytes were paced at 0, 1, or 3 Hz (P0, P1, P3) for up to 24 hours. Cellular tachypacing (P3) mimicked effects of in vivo AT: decreased I(CaL) transient outward (I(to)), unchanged I(CaT), I(Kr), I(Ks), reduced action duration (APD). was P3 2 8 hours but by 55+/-6%...
Coronary artery disease predisposes to atrial fibrillation (AF), but the effects of chronic ischemia/infarction on AF-related substrates are unknown.Regional right myocardial infarction (MI) was created in 40 dogs by ligating an that supplies free wall and not ventricles; 35 sham with same isolated ligated were controls. Dogs observed 8 days after MI subjected open-chest study, vitro optical mapping, and/or cell isolation for patch-clamp Ca(2+) imaging day 8. Holter ECGs showed more...
There is epidemiological evidence that omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of atrial fibrillation (AF), but clinical data are conflicting. The present study assessed effects PUFA on AF in experimental models.We studied oral supplements 2 paradigms: electrical remodeling induced by tachypacing (400 bpm for 1 week) and congestive heart failure-associated structural ventricular (240 weeks). pretreatment did not directly change effective refractory period (128+/-6...
Human multidrug resistance protein 2 (MRP2, encoded by ABCC2) is involved in active efflux of anionic drugs such as methotrexate. MRP2 expressed on the luminal side hepatocytes and renal proximal tubular cells, indicating an important role drug elimination. We postulated that loss-of-function mutations ABCC2, which are Dubin–Johnson syndrome, may be associated with impaired methotrexate elimination increased risk toxicity. studied biological phenotype ABCC2 coding sequence a patient...
Background— Atrial fibrillation impairs atrial contractility, inducing stunning that promotes thromboembolic stroke. Action potential (AP)-prolonging drugs are reported to normalize hypocontractility caused by tachycardia remodeling (ATR). Here, we addressed the role of AP duration (APD) changes in ATR-induced hypocontractility. Methods and Results— ATR (7-day tachypacing) decreased APD (perforated patch recording) ≈50%, contractility (echocardiography, cardiomyocyte video edge detection),...
Angiotensin-II (Ang-II) from extracardiac sources and intracardiac synthesis regulates cardiac homeostasis, with mitogenic growth-promoting effects largely due to altered gene expression. Here, we assessed the possibility that angiotensin-1 (AT1R) or angiotensin-2 (AT2R) receptors on nuclear envelope mediate cardiomyocyte Immunoblots of nucleus-enriched fractions isolated cardiomyocytes indicated presence AT1R AT2R proteins copurified membrane marker nucleoporin-62 histone-3, but not markers...
Atrial fibrillation (AF) causes atrial-tachycardia remodeling (ATR), with enhanced constitutive acetylcholine-regulated K+ current (I(KAChC)) contributing to action potential duration shortening and AF promotion. The underlying mechanisms are unknown.To evaluate the role of protein-kinase C (PKC) isoforms in ATR-induced I(KAChC) activation.Cells from ATR-dogs (400-bpm atrial pacing for 1 week) were compared control dog cells. In vitro tachypaced (TP; 3 Hz) canine cardiomyocytes parallel 1-Hz...
AimsAlthough atrial tachycardia (AT) remodelling promotes agonist-independent, constitutively active, acetylcholine-regulated K+-current (IK,ACh) that increases susceptibility to fibrillation (AF), the underlying changes in IK,Ach channel function are unknown. This study aimed establish how AT affects IK,ACh single-channel function.
Background— TGF-β 1 (transforming growth factor-β ) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of myofibroblasts. It is still elusive, however, which extent alters the electrophysiological phenotype myofibroblasts cardiomyocytes whether it affects proarrhythmic myofibroblast–cardiomyocyte crosstalk observed in vitro. Methods Results— Patch-clamp recordings cultured neonatal rat ventricular revealed that , applied for 24 48...
Membrane lipid composition is a major determinant of cell excitability. In this study, we assessed the role membrane cholesterol in distribution and function Kv1.5-based channels rat cardiac membranes. isolated atrial myocytes, application methyl-beta-cyclodextrin (MCD), an agent that depletes cholesterol, caused delayed increase sustained component, I(kur), which reached steady state approximately 7 min. This effect was prevented by preloading MCD with cholesterol. MCD-increased current...
Transient outward K+ current (I to) downregulation following sustained tachycardia in vivo is usually attributed to tachycardiomyopathy. This study assessed potential direct rate regulation of cardiac I(to) and underlying mechanisms. Cultured adult canine left ventricular cardiomyocytes (37 degrees C) were paced continuously at 1 or 3 Hz for 24 hours. I was recorded with whole-cell patch clamp. The 3-Hz pacing reduced by 44% (P<0.01). Kv4.3 mRNA protein expression significantly (by...
Pulmonary vein (PV)-encircling ablation, which is effective in suppressing atrial fibrillation (AF), damages autonomic ganglia near the PV ostia. This study examined effects of isolation (PVI) vs. peri-PV ganglionic plexus ablation (GPA) two discrete canine AF models: ventricular tachypacing (240 bpm, 2 weeks)-induced congestive heart failure (CHF), and (400 1 week)-induced tachycardia remodeling (ATR). All PVs were isolated with an epicardial radiofrequency clamp nine CHF eight ATR dogs....
Heat shock proteins (HSPs) are a set of endogenous cytoprotective factors activated by various pathological conditions. This study addressed the effects geranylgeranylacetone (GGA), an orally active HSP inducer, on atrial fibrillation (AF) substrate associated with acute ischaemia (AI). Four groups mongrel dogs were studied: (1) group subjected to AI without GGA (AI-CTL, n = 13 dogs); (2) that underwent after pretreatment (120 mg/kg/day; AI-GGA, 12); (3) receiving (n 5); (4) control for...
Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution VF.We addressed hypotheses that there is regional disease-related expression K(ATP) channels in human cardiomyopathic hearts and channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion refractoriness.In a Langendorff model, electric mapping 6 control 9 treatment (10 μmol/L glibenclamide) isolated was...
Rationale: β-Adrenoceptor activation contributes to sudden death risk in heart failure. Chronic β-adrenergic stimulation, as occurs patients with failure, causes potentially arrhythmogenic reductions slow delayed-rectifier K + current (I Ks ). Objective: To assess the molecular mechanisms of I downregulation caused by chronic activation, particularly role exchange protein directly activated cAMP (Epac). Methods and Results: Isolated guinea pig left ventricular cardiomyocytes were incubated...
Atrial fibrillation (AF) is by far the most common cardiac arrhythmia. In about 3% of individuals, AF develops as a primary disorder without any identifiable trigger (idiopathic or historically termed lone AF). line with emerging field autoantibody-related arrhythmias, objective this study was to explore whether autoantibodies targeting ion channels can underlie unexplained AF.Peptide microarray used screen patient samples for autoantibodies. We compared patients (n=37 pre-existent AF; n=14...
Animal models offer invaluable insights into disease mechanisms but cannot entirely mimic the variability and heterogeneity of human populations, nor increasing prevalence multi-morbidity. Consequently, employing samples-such as whole blood or fractions, valvular vascular tissues, myocardium, pericardium, human-derived cells-is essential for enhancing translational relevance cardiovascular research. For instance, myocardial tissue slices, which preserve crucial structural functional...