A5019453857- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiac Arrhythmias and Treatments
- Neuroscience and Neural Engineering
- Groundwater and Isotope Geochemistry
- Receptor Mechanisms and Signaling
- Cardiac pacing and defibrillation studies
- Geology and Paleoclimatology Research
- Water Quality and Resources Studies
- Paleontology and Stratigraphy of Fossils
- Fish Ecology and Management Studies
- Soil and Water Nutrient Dynamics
- ECG Monitoring and Analysis
- Atrial Fibrillation Management and Outcomes
- Geological formations and processes
- Cardiomyopathy and Myosin Studies
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Electrochemical Analysis and Applications
- Cardiac, Anesthesia and Surgical Outcomes
- Anesthesia and Pain Management
- Groundwater flow and contamination studies
- Methane Hydrates and Related Phenomena
- Heart Rate Variability and Autonomic Control
- Connexins and lens biology
University of Tübingen
2023
United States Geological Survey
2012-2022
University of Nevada, Reno
2018-2022
Columbia University
2010-2021
California Water Science Center
2020-2021
University of Insubria
2021
U.S. National Science Foundation
2021
Duke University
2021
University College London
2021
Institute for Fiscal Studies
2021
Background— Ca 2+ leak from the sarcoplasmic reticulum (SR) may play an important role in triggering and/or maintaining atrial arrhythmias, including fibrillation (AF). Protein kinase A (PKA) hyperphosphorylation of cardiac ryanodine receptor (RyR2) resulting dissociation channel-stabilizing subunit calstabin2 (FK506-binding protein or FKBP12.6) causes SR failing hearts and can trigger fatal ventricular arrhythmias. Little is known about RyR2 dysfunction AF, however. Methods Results— Left...
We investigated effects of the paracrine factors secreted by human mesenchymal stem cells (hMSCs) on endothelial cell migration, extracellular matrix invasion, proliferation, and survival in vitro. Human were cultured as a monolayer or three-dimensional aggregates hanging drops (hMSC spheroids). performed analysis medium conditioned hMSCs hMSC spheroids. Concentrations vascular growth factor (VEGF), basic fibroblast factor, angiogenin, procathepsin B, interleukin (IL)-11, bone morphogenic...
We tested the ability of human mesenchymal stem cells (hMSCs) to deliver a biological pacemaker heart. hMSCs transfected with cardiac gene, mHCN2, by electroporation expressed high levels Cs + -sensitive current (31.1±3.8 pA/pF at −150 mV) activating in diastolic potential range reversal −37.5±1.0 mV, confirming as I f -like. The responded isoproterenol an 11-mV positive shift activation. Acetylcholine had no direct effect, but presence isoproterenol, shifted activation 15 mV negative....
The purpose of this study was to determine whether oligonucleotides the size siRNA are permeable gap junctions and a specific for DNA polymerase beta (pol beta) can move from one cell another via junctions, thus allowing inhibit gene expression in directly. To test hypothesis, fluorescently labelled (morpholinos) 12, 16 24 nucleotides length were synthesized introduced into pair using patch pipette. These probes moved through composed connexin 43 (Cx43). Moreover, rate transfer declined with...
Early afterdepolarizations (EADs) are depolarizing potentials that occur during phase 2 or 3 of repolarization. They can induce triggered activity and have been proposed as a cause for arrhythmias in the heart situ. To determine response EADs to interventions analogous those used clinic identifying arrhythmogenic mechanisms, we pacing protocol study sustained drive extrastimuli. Cesium chloride (5 20 mM), which induces intact dog, was isolated canine Purkinje fibers, these were studied by...
Background Microelectrode studies have described a population of cells within the midmyocardium (M cells) displaying steep rate dependence action potential duration (APD) and high V̇ max compared with endocardial (Endo) epicardial (Epi) cells. Methods Results We studied repolarization in different myocardial layers vitro situ. In addition to confirming results earlier studies, we found that after abrupt lengthening cycle length (CL), APDs M reached new steady state faster than Epi or Endo...
Background— We hypothesized that localized overexpression of the hyperpolarization-activated, cyclic nucleotide-gated (HCN2) pacemaker current isoform in canine left atrium (LA) would constitute a novel biological pacemaker. Methods and Results— Adenoviral constructs mouse HCN2 green fluorescent protein (GFP) or GFP alone were injected into LA, terminal studies performed 3 to 4 days later, hearts removed, myocytes examined for native expressed ( I f ). Spontaneous LA rhythms occurred after...
Human mesenchymal stem cells (hMSCs) are a multipotent cell population with the potential to be cellular repair or delivery system provided that they communicate target such as cardiac myocytes via gap junctions. Immunostaining revealed typical punctate staining for Cx43 and Cx40 along regions of intimate cell-to-cell contact between hMSCs. The patterns Cx45 rather were typified by granular cytoplasmic staining. hMSCs exhibited coupling each other, HeLa transfected Cx40, acutely isolated...
Although previous studies have described the electrophysiological and ultrastructural characteristics of human cardiac fibers, no attempt has been made as yet to describe quantitatively relationship between cellular derangements occurring with disease, their clinical manifestations. In this study, we used standard microelectrode techniques record action potential atrial fibers obtained during surgery correlated parameters data. Ultrastructure was studied by optical electron microscopy. We...
Abstract Stem cells show promise for repair of damaged cardiac tissue. Little is known with certainty, however, about the distribution these once introduced in vivo. Previous attempts at tracking delivered stem have been hampered by autofluorescence host tissue and limitations existing labeling techniques. We developed a novel loading approach to stably label human mesenchymal quantum dot (QD) nanoparticles. report optimization validation this long-term technique highlight several important...
Background— We hypothesized that administration of the HCN2 gene to left bundle-branch (LBB) system intact dogs would provide pacemaker function in physiological range heart rates. Methods and Results— An adenoviral construct incorporating green fluorescent protein (GFP) as a marker was injected via catheter under fluoroscopic control into posterior division LBB. Controls were with an GFP alone or saline. Animals monitored electrocardiographically for up 7 days after surgery, at which time...
We used standard microelectrode techniques to record action potentials of human right atrial fibers obtained during cardiac surgery, and correlated these with clinical preoperative ECG data. Human were classified as follows: Group A (ten patients) had a maximum diastolic potential (MDP) -71.4 +/- 5.1mV (mean SD), that primarily fast responses. These atria normal or slightly dilated. In group B (12 MDP was 50.3 5.7 mV; slow responses the moderately markedly Atrial arrhythmias occurred in four...
Biological pacemaking has been performed with viral vectors, human embryonic stem cells, and adult mesenchymal cells (hMSCs) as delivery systems. Only are data available regarding stability for >2 to 3 weeks, here, immunosuppression used facilitate survival of xenografts. The purpose the present study was determine whether hMSCs provide stable impulse initiation over 6 weeks without use immunosuppression, "dose" that ensures function this period, catecholamine responsiveness hMSC-packaged...
Isolated canine Purkinje fiber bundles (PF) were perfused with the blood of intact donor dogs to correlate changes induced by ouabain (O) in PF transmembrane potential (TP) and ECG. O was administered intravenously donor, standard microelectrode technics used record TP. The only significant effect prior occurrence toxic arrhythmias induction ST-T wave ECG prolongation action duration (APD). Early toxicity defined as onset junctional or ventricular premature contractions tachycardia....
Standard microelectrode techniques were used to determine the effects of verapamil, 2 x 10 -7 1 -5 M, on electrophysiologic properties isolated canine cardiac Purkinje fibers. Verapamil, -6 had no effect fiber action potential (AP). altered repolarization primarily by enhancing phase and increasing slope 2. ≥6 more pronounced AP decreased amplitude, resting membrane potential, maximum rate rise 0 responsiveness as well. The ratio duration effective refractory period was unchanged verapamil....
Journal Article Early electrical remodeling in rabbit pulmonary vein results from trafficking of intracellular SK2 channels to membrane sites Get access Nazira Özgen, Özgen aCenter for Molecular Therapeutics, College Physicians and Surgeons Columbia University, New York, United StatesbDepartment Pharmacology, States Search other works by this author on: Oxford Academic PubMed Google Scholar Wen Dun, Dun bDepartment Eugene A. Sosunov, Sosunov Evgeny P. Anyukhovsky, Anyukhovsky Masanori...
About 130 million people in the United States rely on groundwater for drinking water, and need high-quality drinking-water supplies becomes more urgent as our population grows. Although is a safe, reliable source of water millions nationwide, high concentrations some chemical constituents can pose potential human-health concerns. Some these contaminants come from rocks sediments aquifers themselves, others are chemicals that we use agriculture, industry, day-to-day life. When contaminated,...