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255
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Introduction
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January 2008 - present
January 1997 - December 2012
Publications
Publications (255)
Aims
The resolution of inflammation is modulated by specialized pro-resolving lipid mediators (SPMs), which can be modified in some cardiovascular diseases. Among them, RvD1 and LXA4 prevent atrial fibrillation (AF) remodeling in the atria and cardiac hypertrophy, respectively in animal models. However, little is known about their electrophysiologi...
The atrioventricular node (AVN) is a crucial component of the cardiac conduction system. Despite its pivotal role in regulating the transmission of electrical signals between atria and ventricles, a comprehensive understanding of the cellular electrophysiological mechanisms governing AVN function has remained elusive. This paper presents a detailed...
Background: Cardiac pacemaking remains an unsolved matter from many perspectives. Extensive experimental and computational studies have been performed to describe the sinoatrial physiology across different scales, from the molecular to clinical levels. Nevertheless, the mechanism by which a heartbeat is generated inside the sinoatrial node and prop...
Human induced pluripotent stem cells–derived cardiomyocytes have revolutionized the field of regenerative medicine, offering unparalleled potential for in–vitro modeling of normal and pathological human cardiomyocytes. The ability to produce stem cardiac myocytes in abundance has opened new avenues for drug efficacy and safety testing, as well as t...
Caveolae constitute membrane microdomains where receptors and ion channels functionally interact. Caveolin-3 (cav-3) is the key structural component of muscular caveolae. Mutations in CAV3 lead to caveolinopathies, which result in both muscular dystrophies and cardiac diseases. In cardiomyocytes, cav-1 participates with cav-3 to form caveolae; skel...
Atrial Fibrillation (AF) is the most common arrhythmia with a complex pathophysiology. In experiments, it becomes quite challenging to dissect the key mechanisms behind the AF induced remodeling effect. Using the power of computational modeling, we have developed a chronic atrial fibrillation version of our recently developed human atrial electrome...
Mechano‐electric regulations (MER) play an important role in the maintenance of cardiac performance. Mechano‐calcium and mechano‐electric feedback (MCF and MEF) pathways adjust the cardiomyocyte contractile force according to mechanical perturbations and affects electro‐mechanical coupling. MER integrates all these regulations in one unit resulting...
Regenerative cardiology recently advanced in patient–specific medicine by employing somatic cells to derive pluripotent stem cells and differentiate them into cardiomyocytes. Resulting populations present an immature phenotype; the Dynamic Clamp technique is a popular experimental manipulation to induce electronic maturation towards an adult phenot...
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) constitute a mixed population of ventricular-, atrial-, nodal-like cells, limiting the reliability for studying chamber-specific disease mechanisms. Previous studies characterised CM phenotype based on action potential (AP) morphology, but the classification criteria were still...
Atrial fibrillation (AF) is one of the most investigated arrhythmias since it is associated with a five-fold increase in the risk of strokes. Left atrium dilation and unbalanced and irregular contraction caused by AF favour blood stasis and, consequently, stroke risk. The left atrial appendage (LAA) is the site of the highest clots formation, incre...
Purpose
Extracorporeal ultrafiltration is an attractive alternative to diuretics for removing excess plasma water in critically ill patients suffering from fluid overload. In continuous renal replacement therapy (CRRT), ultrafiltration occurs in isolated form (SCUF) or supplemented by replacement fluid infusion (CVVH) and the net fluid removal rate...
Both experimental and modeling studies have attempted to determine mechanisms by which a small anatomical region, such as the sinoatrial node (SAN), can robustly drive electrical activity in the human heart. However, despite many advances from prior research, important questions remain unanswered. This study aimed to investigate, through mathematic...
Since its discovery, the sinoatrial node (SAN) has represented a fascinating and complex matter of research. Despite over a century of discoveries, a full comprehension of pacemaking has still to be achieved. Experiments often produced conflicting evidence that was used either in support or against alternative theories, originating intense debates....
Contractility has become one of the main readouts in computational and experimental studies on cardiomyocytes. Following this trend, we propose a novel mathematical model of human ventricular cardiomyocytes electromechanics, BPSLand, by coupling a recent human contractile element to the BPS2020 model of electrophysiology. BPSLand is the result of a...
Both experimental and modeling studies have attempted to determine mechanisms by which a small anatomical region, such as the sinoatrial node (SAN), can robustly drive electrical conduction in the human heart. However, despite important advances from prior research, important questions remain unanswered. This study aimed to investigate, through mat...
Monitoring bone tissue engineered (TEed) constructs during their maturation is important to ensure the quality of applied protocols. Several destructive, mainly histochemical, methods are conventionally used to this aim, requiring the sacrifice of the investigated samples. This implies (i) to plan several scaffold replicates, (ii) expensive and tim...
Atrial fibrillation (AF) is the most common cardiac arrhythmia and catheter mapping has been proved to be an effective approach for detecting AF drivers to be targeted by ablation. Among drivers, the so-called rotors have gained the most attention: their identification and spatial location could help to understand which patient-specific mechanisms...
The sinoatrial node (SAN) is the natural pacemaker of the mammalian heart. It has been the subject of several mathematical studies, aimed at reproducing its electrical response under normal sinus rhythms, as well as under various conditions. Such studies were traditionally done using data from rabbit SAN cells. More recently, human SAN cell data ha...
Human-based computational models are a powerful tool that complements the experimental approaches and can improve our understanding of individual components
of the heart by integrating them into one system. This paper aims to couple and calibrate a human atrial electro-mechanical model to analyse the coupling effects and inotropic interventions on...
PurposeGenerator impedance (Im) mapping with constant contact force (CF) by tip catheter at PV isolation (PVI) was assessed for a proposal of tissue characterization at PV-LA junction (PV-LAJ).Methods
In this observational, prospective, single-center study, Im mapping at constant CF = 10 g (± 2 g) was performed before PVI at PV-LAJ. PV in-vein, PV...
The sinoatrial node (SAN) is the natural pacemaker of the mammalian heart. It has been the the subject of several mathematical studies, aimed at reproducing its electrical response under normal sinus rhythms, as well as under various conditions. Such studies were traditionally done using data from rabbit SAN cells. More recently, human SAN cell dat...
The sinoatrial node (SAN) is the natural pacemaker of the mammalian heart. It has been the the subject of several mathematical studies, aimed at reproducing its electrical response under normal sinus rhythms, as well as under various conditions. Such studies were traditionally done using data from rabbit SAN cells. More recently, human SAN cell dat...
Funding Acknowledgements
Type of funding sources: None.
Background
Percutaneous endocardial left atrial appendage (LAA) occlusion (LAAO) in non-valvular atrial fibrillation (AF) seems comparable to anticoagulation therapy (OAC) as regards thromboembolic risk reduction with a possible additional decrease in major bleeding. LAAO is currently limited...
As drugs can be multichannel blockers it is important to assess their cardiac safety taking into account multiple currents. In silico action potential (AP) models have been proposed for being able to integrate drugs effect on ionic currents and generate the resulting AP. However, a mathematical description of drug effects is required, which could b...
Diseases caused by alterations of ionic concentrations are frequently observed challenges and play an important role in clinical practice. The clinically established method for the diagnosis of electrolyte concentration imbalance is blood tests. A rapid and non-invasive point-of-care method is yet needed. The electrocardiogram (ECG) could meet this...
Measurement of carbon dioxide (CO2) in medical applications is a well-established method for monitoring patient’s pulmonary function in a noninvasive way widely used in emergency, intensive care, and during anesthesia. Even in extracorporeal-life support applications, such as Extracorporeal Carbon Dioxide Removal (ECCO2R), Extracorporeal Membrane O...
End-stage chronic kidney disease (CKD) patients are facing a 30% rise for the risk of lethal cardiac events (LCE) compared to non-CKD patients. At the same time, these patients undergoing dialysis experience shifts in the potassium concentrations. The increased risk of LCE paired with the concentration changes suggest a connection between LCE and c...
Background
An automated method for 3D reconstruction of coronary sinus (CS) lead’s pacing cathode trajectory (3DTJ) was proposed to acutely predict long term left ventricular (LV) mechanic response to cardiac resynchronization therapy (CRT). Preliminary data showed that 3DTJ at biventricular pacing (BIV) start changed in CRT responders (R) to be, b...
The importance of electrolyte concentrations for cardiac function is well established. Electrolyte variations can lead to arrhythmias onset, due to their important role in the action potential (AP) genesis and in maintaining cell homeostasis. However, most of the human AP computer models available in literature were developed with constant electrol...
Cardiac Purkinje cells (PCs) are implicated in lethal arrhythmias caused by cardiac diseases, mutations, and drug action. However, the pro-arrhythmic mechanisms in PCs are not entirely understood, particularly in humans, as most investigations are conducted in animals. The aims of this study are to present a novel human PCs electrophysiology biophy...
High-throughput in vitro drug assays have been impacted by recent advances in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) technology and by contact-free all-optical systems simultaneously measuring action potential (AP) and Ca²⁺ transient (CaTr). Parallel computational advances have shown that in silico simulations can pr...
Human-based modelling and simulations are becoming ubiquitous in biomedical science due to their ability to augment experimental and clinical investigations. Cardiac electrophysiology is one of the most advanced areas, with cardiac modelling and simulation being considered for virtual testing of pharmacological therapies and medical devices. Curren...
This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and Drug Administration–sponsored Think Tank Meeting on May 22, 2018. The meeting was convened to evalu...
High-throughput in vitro drug assays have been impacted by recent advances in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) technology and by contact-free all-optical systems simultaneously measuring action potential (AP) and Ca ²⁺ transient (CaTr). Parallel computational advances have shown that in silico models can predict...
Changes of serum and extracellular ion concentrations occur regularly in patients with chronic kidney disease (CKD). Recently, hypocalcemia, i.e. a decrease of the extracellular calcium concentration [Ca2+]o, has been suggested as potential pathomechanism contributing to the unexplained high rate of sudden cardiac death (SCD) in CKD patients. In pa...
Background
Hemodialysis (HD) sessions induce changes in plasma electrolytes that lead to modifications of QT interval, virtually associated with dangerous arrhythmias. It is not known whether such a phenomenon occurs even during peritoneal dialysis (PD). The aim of the study is to analyze the relationship between dialysate and plasma electrolyte mo...