A5034297723- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiac Arrhythmias and Treatments
- Cardiac pacing and defibrillation studies
- ECG Monitoring and Analysis
- Neuroscience and Neural Engineering
- Cardiac Imaging and Diagnostics
- Cardiomyopathy and Myosin Studies
- Receptor Mechanisms and Signaling
- Electrical and Bioimpedance Tomography
- Advanced MRI Techniques and Applications
- Cardiovascular Effects of Exercise
- Atrial Fibrillation Management and Outcomes
- Neuroscience and Neuropharmacology Research
- Cardiovascular Function and Risk Factors
- stochastic dynamics and bifurcation
- Electrochemical Analysis and Applications
- Heart Rate Variability and Autonomic Control
- Non-Invasive Vital Sign Monitoring
- EEG and Brain-Computer Interfaces
- Neural dynamics and brain function
- Control Systems and Identification
- Connexins and lens biology
- Fault Detection and Control Systems
- Congenital Heart Disease Studies
Washington University in St. Louis
2014-2024
Barnes-Jewish Hospital
2014-2022
Case Western Reserve University
1999-2020
University College London
2017
St Bartholomew's Hospital
2017
Pediatrics and Genetics
2017
Leiden University
2017
Johns Hopkins Hospital
2017
MetroHealth Medical Center
2016
HealthInsight
2014-2015
A mathematical model of the cardiac ventricular action potential is presented. In our previous work, membrane Na+ current and K+ currents were formulated. The present article focuses on processes that regulate intracellular Ca2+ depend its concentration. presented here for mammalian based mostly guinea pig cell. However, it provides framework modeling other types cells with appropriate modifications made to account species differences. following are formulated: through L-type channel (ICa),...
A mathematical model of the membrane action potential mammalian ventricular cell is introduced. The based, whenever possible, on recent single-cell and single-channel data incorporates possibility changing extracellular potassium concentration [K]o. fast sodium current, INa, characterized by upstroke velocity (Vmax = 400 V/sec) slow recovery from inactivation. time-independent IK1, includes a negative-slope phase displays significant crossover phenomenon as [K]o varied. time-dependent IK,...
Cellular electrophysiology experiments, important for understanding cardiac arrhythmia mechanisms, are usually performed with channels expressed in non myocytes, or non-human myocytes. Differences between cell types and species affect results. Thus, an accurate model the undiseased human ventricular action potential (AP) which reproduces a broad range of physiological behaviors is needed. Such requires extensive experimental data, but essential elements have been unavailable. Here, we...
In cardiac tissue, reduced membrane excitability and gap junction coupling both slow conduction velocity of the action potential. However, ionic mechanisms for two conditions are very different. We explored, using a multicellular theoretical fiber, functional role fast sodium current, INa, L-type calcium ICa(L), during slowing fiber conditions. A safety factor (SF) was formulated computed each condition. Reduced caused lower SF as decreased. contrast, paradoxical increase in The opposite...
Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and delivery precise ablative radiation stereotactic body therapy (SBRT). We combined these techniques to perform catheter-free, electrophysiology-guided, radioablation for ventricular tachycardia.We targeted arrhythmogenic scar regions by combining anatomical during tachycardia that was induced means an implantable cardioverter-defibrillator (ICD). SBRT simulation, planning, treatments...
The action potential model presented in our accompanying article this journal is used to investigate phenomena that involve dynamic changes of [Ca2+]i, as described below. Delayed afterdepolarizations (DADs) are induced by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), which, turn, activates both Na(+)-Ca2+ exchanger (INaCa) and a nonspecific Ca(2+)-activated current (Ins(Ca)). relative contributions INaCa Ins(Ca) generation DADs different under degrees overload. Early (EADs)...
Abstract Two distinct delayed rectifier K + currents, I Kr and Ks , were found recently in ventricular cells. We formulated these currents theoretically investigated their roles action potential repolarization the restitution of duration (APD). The Luo-Rudy (L-R) model was used simulations. single current replaced by . Our results show that is major outward during plateau repolarization. A specific block either or can effectively prolong APD to same degree. Therefore, channel provides a...
Body surface electrocardiograms and electrograms recorded from the surfaces of heart are basis for diagnosis treatment cardiac electrophysiological disorders arrhythmias. Given recent advances in understanding molecular mechanisms arrhythmia, it is important to relate these electrocardiographic waveforms cellular processes. This modeling study establishes following principles: (1) voltage gradients created by heterogeneities slow-delayed rectifier ( I Ks ) transient outward potassium current...
Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking.We conducted a phase I/II trial in adults with treatment-refractory episodes VT or cardiomyopathy related to premature contractions (PVCs). Arrhythmogenic scar regions were targeted by combining anatomic and electric imaging standard therapy workflow followed...
Background— Various mechanisms of atrial fibrillation (AF) have been demonstrated experimentally. Invasive methods to study these in humans limitations, precluding continuous mapping both atria with sufficient resolution. In this article, we present biatrial epicardial activation sequences AF using noninvasive electrocardiographic imaging (ECGI). Methods and Results— the testing phase, ECGI accuracy was evaluated by comparing coregistered CARTO images during pacing 6 patients. Additionally,...
Background: Early repolarization in the inferolateral leads has been recently recognized as a frequent syndrome associated with idiopathic ventricular fibrillation (VF). We report case of patient presenting dramatic changes ECG association recurrent VF whom novel genetic variant identified. Case Report: This young female (14 years) was resuscitated 2001 following an episode sudden death due to VF. All examinations including coronary angiogram ergonovine injection, MRI, and flecainide or...
Excitation-contraction coupling in striated muscle requires proper communication of plasmalemmal voltage-activated Ca2+ channels and release on sarcoplasmic reticulum within junctional membrane complexes. Although previous studies revealed a loss complexes embryonic lethality germ-line junctophilin-2 (JPH2) knockout mice, it has remained unclear whether JPH2 plays an essential role complex formation the Ca(2+)-induced Ca(2+) process heart. Our recent work demonstrated loss-of-function...
Background —A growing body of evidence suggests that heterogeneity ion channel expression and electrophysiological characteristics is an important property the ventricular myocardium. The 2 components delayed rectifier potassium current, I Kr (rapid) Ks (slow), play a dominant role in repolarization action potential are determinants its duration. Methods Results —In this report, effects heterogeneities on duration (APD) rate dependence (adaptation) studied with use LRd model mammalian cell....
Computational biology is a powerful tool for elucidating arrhythmogenic mechanisms at the cellular level, where complex interactions between ionic processes determine behavior. A novel theoretical model of canine ventricular epicardial action potential and calcium cycling was developed used to investigate underlying Ca2+ transient (CaT) duration (APD) rate dependence.The Ca2+/calmodulin-dependent protein kinase (CaMKII) regulatory pathway integrated into model, which included Ca2+-release...
Background — Complex physiological interactions determine the functional consequences of gene abnormalities and make mechanistic interpretation phenotypes extremely difficult. A recent example is a single mutation in C terminus cardiac Na + channel, 1795insD. The causes two distinct clinical syndromes, long QT (LQT) Brugada, leading to life-threatening arrhythmias. Coexistence these syndromes seemingly paradoxical; LQT associated with enhanced channel function, Brugada reduced function....
It is well known that the sodium current ( I Na ) and degree of gap-junctional electrical coupling are key determinants action potential (AP) conduction in cardiac tissue. Immunohistochemical studies have shown channels (NaChs) preferentially located intercalated disks (IDs). Using dual immunocytochemical staining, we confirmed colocalization NaChs with connexin43 cultures neonatal rat ventricular myocytes. In mathematical simulations using Luo-Rudy dynamic model AP, assessed hypothesis...
Background The goal of noninvasive electrocardiographic imaging (ECGI) is to determine electric activity the heart by reconstructing maps epicardial potentials, excitation times (isochrones), and electrograms from data measured on body surface. Methods Results Local electrocardiac events were initiated pacing a dog in human torso–shaped tank. Body surface potential measurements (384 electrodes) used compute potentials noninvasively. accuracy reconstructed was evaluated direct comparison ones...