A5061841505- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiac Arrhythmias and Treatments
- Atrial Fibrillation Management and Outcomes
- Caveolin-1 and cellular processes
- Cardiomyopathy and Myosin Studies
- Neuroscience and Neural Engineering
- Cardiac pacing and defibrillation studies
- Tissue Engineering and Regenerative Medicine
- Heart Rate Variability and Autonomic Control
- Receptor Mechanisms and Signaling
- Cardiac Ischemia and Reperfusion
- Connexins and lens biology
- Bat Biology and Ecology Studies
- Pluripotent Stem Cells Research
- Cardiovascular Function and Risk Factors
- 3D Printing in Biomedical Research
- Electrospun Nanofibers in Biomedical Applications
- Physiological and biochemical adaptations
- Electrochemical Analysis and Applications
- Cardiac Arrest and Resuscitation
- Congenital heart defects research
- Erythrocyte Function and Pathophysiology
- Neuroscience of respiration and sleep
- Fuel Cells and Related Materials
University of Wisconsin–Madison
2016-2025
Krasnoyarsk Scientific Center
2024
Institute of Biophysics
2024
University of Wisconsin System
2019-2020
Imperial College London
2013-2017
Indian Institute of Technology Hyderabad
2016
Hammersmith Hospital
2015-2016
Johns Hopkins University
2016
Universität Hamburg
2016
University Medical Center Hamburg-Eppendorf
2016
Rationale: Transmural dispersion of repolarization has been shown to play a role in the genesis ventricular tachycardia and fibrillation different animal models heart failure (HF). Heterogeneous changes within midmyocardial population cells have considered an important contributor HF phenotype. However, there is limited electrophysiological data from human heart. Objective: To study remodeling transmural failing nonfailing hearts. Methods Results: We optically mapped action potential...
Sinus node dysfunction (SND) is a major public health problem that associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little known about the molecular cellular mechanisms cause SND. Most SND occurs in setting heart failure hypertension, conditions are marked by elevated circulating angiotensin II (Ang II) increased oxidant stress. Here, we show oxidized calmodulin kinase (ox-CaMKII) biomarker for patients dogs disease determinant mice....
Several arrhythmogenic mechanisms have been inferred from animal heart failure models. However, the translation of these hypotheses is difficult because lack functional human data. We aimed to investigate electrophysiological substrate for arrhythmia in end-stage nonischemic cardiomyopathy.We optically mapped coronary-perfused left ventricular wedge preparations hearts with cardiomyopathy (heart failure, n=10) and nonfailing (NF, n=10). Molecular remodeling was studied immunostaining,...
Background— Excitation-contraction (EC) coupling is altered in end-stage heart failure. However, spatial heterogeneity of this remodeling has not been established at the tissue level failing human heart. The objective article was to study functional excitation-contraction and calcium handling nonfailing hearts. Methods Results— We simultaneously optically mapped action potentials transients coronary perfused left ventricular wedge preparations from (n=6) (n=5) Our major findings are...
Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study sinoatrial node (SAN) dysfunction due loss of CASQ2.In vivo electrocardiogram (ECG) monitoring, vitro high-resolution optical mapping, confocal imaging intracellular Ca(2+) cycling, 3D immunohistology were performed wild-type...
Disruption in subcellular targeting of Ca(2+) signaling complexes secondary to changes cardiac myocyte structure may contribute the pathophysiology a variety diseases, including heart failure (HF) and certain arrhythmias.To explore microdomain-targeted remodeling ventricular L-type channels (LTCCs) HF.Super-resolution scanning patch-clamp, confocal fluorescence microscopy were used distribution single LTCCs different membrane microdomains nonfailing failing human rat myocytes. both species...
Distinct subpopulations of L-type calcium channels (LTCCs) with different functional properties exist in cardiomyocytes. Disruption cellular structure may affect LTCC a microdomain-specific manner and contribute to the pathophysiology cardiac diseases, especially cells lacking organized transverse tubules (T-tubules) such as atrial myocytes (AMs).Isolated rat human AMs were characterized by scanning ion conductance, confocal, electron microscopy. Half possessed T-tubules structured...
Although sinoatrial node (SAN) dysfunction is a hallmark of human heart failure (HF), the underlying mechanisms remain poorly understood. We aimed to examine role adenosine in SAN and tachy-brady arrhythmias chronic HF.We applied multiple approaches characterize structure, function, A1 receptor expression control (n=17) 4-month tachypacing-induced HF (n=18) dogs. Novel intramural optical mapping coronary-perfused right atrial preparations revealed that (10 μmol/L) markedly prolonged...
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CM) may provide an important bridge between animal models and the intact myocardium. Fulfilling this potential is hampered by their relative immaturity, leading to poor physiological responsiveness. hiPSC-CMs grown in traditional two-dimensional (2D) culture lack a t-tubular system, have only rudimentary intracellular calcium-handling systems, express predominantly embryonic sarcomeric protein isoforms, preferentially...
The mouse is widely used as a genetic platform to investigate the molecular mechanisms of sinoatrial node (SAN) pacemaking. Recently, it has been shown that isolated SAN cells from ankyrin-B (AnkB)-deficient mice display severe pacemaking dysfunction similar individuals harboring ankyrin 2 allele variants. However, these results have limited only and thus did not evaluate functional anatomy distributed atrial pacemaker complex (e.g., dynamic interaction primary subsidiary pacemakers). We...
Background— Numerous studies implicate the sinoatrial node (SAN) as a participant in atrial arrhythmias, including flutter (AFL) and fibrillation (AF). However, direct role of SAN has never been described. Methods Results— The was optically mapped coronary perfused preparations from normal canine hearts (n=17). Optical action potentials were recorded during spontaneous rhythm, overdrive pacing, AF/AFL induced by acetylcholine (ACh; 0.3 to 3 μmol/L) and/or isoproterenol (Iso; 0.2 1 μmol/L)....
Cardiomyocyte β2-adrenergic receptor (β2AR) cyclic adenosine monophosphate (cAMP) signalling is regulated by the receptors' subcellular location within transverse tubules (T-tubules), via interaction with structural and regulatory proteins, which form a signalosome. In chronic heart failure (HF), β2ARs redistribute from T-tubules to cell surface, disrupts functional signalosomes leads diffuse cAMP signalling. However, consequences of changes upon β2AR-cAMP during progression hypertrophy...
The structure-function relationship in the atrioventricular junction (AVJ) of various animal species has been investigated detail; however, less is known about human AVJ. In this study, we performed high-resolution optical mapping AVJ (n = 6) to define its pacemaker properties and response autonomic stimulation.Isolated, coronary-perfused preparations from failing hearts 6, 53 ± 6 years) were optically mapped using near-infrared, voltage-sensitive dye, di-4-ANBDQBS, with isoproterenol (1...
Reentrant arrhythmias involving the sinoatrial node (SAN), namely SAN reentry, remain one of most intriguing enigmas cardiac electrophysiology. The goal present study was to elucidate mechanism micro-reentry in canine hearts with post-myocardial infarction (MI) structural remodeling.In vivo, Holter monitoring revealed ventricular and dysfunctions post-left MI (6-15 weeks) dogs (n=5) compared control (n=4). In vitro, high-resolution near-infrared optical mapping intramural activation...
Background Atrial fibrillation often occurs in the setting of hypertension and associated atrial dilation with pathologically increased cardiomyocyte stretch. In dilation, mechanoelectric feedback has been linked to development ectopic beats that trigger paroxysmal mainly originating from pulmonary veins ( PVs ). However, precise mechanisms remain poorly understood. Methods Results We identify mechanosensitive, swelling‐activated chloride ion channels I C l,swell ) as a crucial component...