A5063436173- Cardiac electrophysiology and arrhythmias
- Atrial Fibrillation Management and Outcomes
- Ion channel regulation and function
- Cardiac Arrhythmias and Treatments
- Cardiac pacing and defibrillation studies
- ECG Monitoring and Analysis
- Neuroscience and Neural Engineering
- Cardiac Ischemia and Reperfusion
- Receptor Mechanisms and Signaling
- Heart Rate Variability and Autonomic Control
- Electron Spin Resonance Studies
- Advanced Fluorescence Microscopy Techniques
- Force Microscopy Techniques and Applications
- Cardiac Arrest and Resuscitation
- Electrochemical sensors and biosensors
- Integrated Circuits and Semiconductor Failure Analysis
- Adenosine and Purinergic Signaling
- Cardiovascular and Diving-Related Complications
- Nitric Oxide and Endothelin Effects
- Obstructive Sleep Apnea Research
- Electrolyte and hormonal disorders
University of Glasgow
2012-2023
University of Bologna
2015
Ospedale Policlinico San Martino
2015
University of Michigan–Ann Arbor
2011
Heidelberg University
2011
University Medical Centre Mannheim
2011
University Hospital Heidelberg
2011
University of California, Davis
2011
British Heart Foundation
2008-2010
GlaxoSmithKline (France)
2008
Rationale: Understanding atrial fibrillation (AF) requires integrated understanding of ionic currents and Ca 2+ transport in remodeled human atrium, but appropriate models are limited. Objective: To study AF, we developed a new action potential (AP) model, derived from experimental results our ventricular myocyte model. Methods Results: Atria versus ventricles have lower I K1 , resulting more depolarized resting membrane (≈7 mV). We used higher to,fast density removed to,slow included an...
Objective: To investigate changes in human atrial single cell functional electrophysiological properties associated with chronic fibrillation (AF), and the contribution to these of accompanying ion current changes. Methods: The whole patch clamp technique was used record action potentials, effective refractory period (ERP) currents, absence presence drugs, enzymatically isolated myocytes from 11 patients (<6 months) AF 39 sinus rhythm. Results: Stimulation at high rates (up 600 beats/min)...
Rapid atrial arrhythmias such as fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of ectopic activity from electrocardiogram (ECG) can help diagnose early onset AF in a cost-effective manner. The complex rapid electrical during makes it difficult obtain detailed information on activation using standard 12-lead ECG alone. Compared conventional ECG, more lead configurations may provide further about spatio-temporal dynamics body...
Key points The shape of the cardiac atrial action potential is influenced by flow a transient outward K + current ( I TO ) across muscle cell membranes. Whether changes in could alter potentials ways that affect mechanisms abnormal heart rhythms (arrhythmias) unclear, because currently available blocking drugs are non‐selective. We used ‘dynamic‐clamp’ technique, for first time cells isolated from patients, and rabbits, to electrically simulate selective during recording. found decrease...
AimsAtrial fibrillation (AF) is increased in patients with heart failure resulting from myocardial infarction (MI). We aimed to determine the effects of chronic ventricular MI rabbits on susceptibility AF, and underlying atrial electrophysiological Ca2+-handling mechanisms.
Introduction: We investigated whether post‐cardiac surgery (CS) new‐onset atrial fibrillation (AF) is predicted by pre‐CS cellular electrophysiology, and the antiarrhythmic effect of beta‐blocker therapy may involve pharmacological remodeling. Methods Results: Atrial myocytes were obtained from consenting patients in sinus rhythm, just prior to CS. Action potentials ion currents recorded using whole‐cell patch‐clamp technique. Post‐CS AF occurred 53 212 (25%). Those with post‐CS older than...
The goal was to terminate atrial fibrillation (AF) by targeting atrioventricular differences in ionic properties.Optical mapping used record electrical activity during carbachol (0.25-0.5 μM)-induced AF pig hearts. atrial-specific current, I(Kur), blocked with 100 μM 4-aminopyridine (4-AP) or 0.5 DPO-1. Hearts and ventricular (VF) were also subjected increasing levels of extracellular K(+) ([K(+)](o): 6-12 mM), compared controls (4 mM). We hypothesized that due the more negative steady-state...
Chronic beta-adrenoceptor antagonist (beta-blocker) treatment reduces the incidence of reversion to AF in patients, possibly via an adaptive myocardial response. However, underlying electrophysiological mechanisms are presently unclear. We aimed investigate changes human atrial cells associated with chronic beta-blockers and other cardiovascular-acting drugs.Myocytes were isolated enzymatically from right appendage 40 consenting patients who sinus rhythm. The cellular action potential...
Objective: To assess the contribution of Na, K pump current (Ip) to action potential duration (APD) and effective refractory period (ERP) in human atrial cells, investigate whether Ip contributes changes APD ERP associated with chronic fibrillation (AF). Methods: Action potentials ion currents were recorded by whole-cell patch clamp myocytes isolated from consenting patients undergoing cardiac surgery, who sinus rhythm (SR) or AF (>3 months). Results: In cells SR, blocker, ouabain (10 μM)...
Atrial anti-arrhythmic effects of β-adrenoceptor antagonists (β-blockers) may involve both a suppression pro-arrhythmic catecholamines, and an adaptational electrophysiological response to chronic β-blocker use; so-called ‘pharmacological remodelling’. In human atrium, such remodelling decreases the transient outward (Ito) inward rectifier (IK1) K+ currents, increases cellular action potential duration (APD) effective refractory period (ERP). However, consequences these changes on mechanisms...
Key points Early‐afterdepolarizations (EADs) are abnormal action potential oscillations and a known cause of cardiac arrhythmias. Ventricular EADs involve reactivation Ca 2+ current ( I CaL ) in its ‘window region’ voltage range. However, electrical mechanisms atrial EADs, fibrillation, poorly understood. Atrial cells were obtained from consenting patients undergoing heart surgery, as well rabbits. was blocked with nifedipine then hybrid patch clamp/mathematical‐modelling technique, ‘dynamic...
Although atrial fibrillation ablation is increasingly used for rhythm control therapy, antiarrhythmic drugs (AADs) are commonly used, either alone or in combination with ablation. The effectiveness of AADs highly variable. Previous work from our group suggests that alterations resting membrane potential (RMP) induced by low Pitx2 expression could explain the variable effect flecainide.The purpose this study was to assess whether atrial/cardiac RMP modify multiple clinically AADs.The sodium...
5-Hydroxytryptamine (5-HT) is proarrhythmic in atrial cells from patients sinus rhythm (SR) via activation of 5-HT4 receptors, but its effects with fibrillation (AF) are unknown. The whole-cell perforated patch-clamp technique was used to record L-type Ca2+ current (ICaL), action potential duration (APD) and arrhythmic activity at 37°C enzymatically isolated obtained undergoing cardiac surgery, SR or chronic AF. In the AF group, 5-HT (10μM) produced an increase ICaL 115±21% above control...
Objectives: Firstly, to compare effects of adenosine on membrane potential and refractoriness in AV nodal atrial cells. Secondly, assess the contribution IKAdo ICaL its functional electrophysiological properties two cell types. Methods: The whole patch clamp technique was used record action potentials ion currents left myocytes isolated enzymatically from rabbit hearts. Results: Adenosine (10 μM) caused similar hyperpolarisation shortening duration (APD) both types: maximum diastolic...
5‐Hydroxytryptamine (5‐HT) has been postulated to play a proarrhythmic role in the human atria via stimulation of 5‐HT 4 receptors. The aims this study were examine effects on L‐type Ca 2+ current ( I CaL ) action potential duration (APD), effective refractory period (ERP) and arrhythmic activity atrial cells, assess prior treatment with β ‐adrenoceptor antagonists. Isolated myocytes, from right appendage 27 consenting patients undergoing cardiac surgery who sinus rhythm, studied using...
Prucalopride is a selective 5-hydroxytryptamine type 4 (5-HT<sub>4</sub>) receptor agonist developed for the treatment of gastrointestinal disorders. The endogenous 5-HT acting via 5-HT<sub>4</sub> receptors increases L-type Ca<sup>2+</sup> current (I<sub>CaL</sub>) with potentially proarrhythmic consequences (Pau et al., 2003). aims this study were to investigate effects prucalopride on I<sub>CaL</sub>, action potentials, refractory period, and arrhythmic activity in human atrial myocytes,...
Introduction: The development of improved diagnosis, management and treatment strategies for human atrial fibrillation (AF) is a significant important challenge in order to improve quality life millions reduce the substantial social-economic costs condition. As complex condition demonstrating high variability relation other cardiac conditions, study AF requires approaches from multiple disciplines including single-cell experimental electrophysiology computational modelling. Models cells are...