A5038576548- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiac Arrhythmias and Treatments
- ECG Monitoring and Analysis
- Cardiac pacing and defibrillation studies
- Heart Rate Variability and Autonomic Control
- Retinal Imaging and Analysis
- Cardiovascular Effects of Exercise
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Cardiovascular Health and Disease Prevention
- Retinal and Optic Conditions
- Functional Brain Connectivity Studies
- Cardiac Imaging and Diagnostics
- Lipoproteins and Cardiovascular Health
- Blood Pressure and Hypertension Studies
- Mental Health Research Topics
- Cerebrovascular and Carotid Artery Diseases
- Cardiovascular Function and Risk Factors
- Connexins and lens biology
- Neural and Behavioral Psychology Studies
- Retinal Diseases and Treatments
- Neuroscience and Neural Engineering
- Cardiovascular Disease and Adiposity
- Glycogen Storage Diseases and Myoclonus
- Cardiac Valve Diseases and Treatments
University Children's Hospital Tübingen
2018-2025
University of Tübingen
2015-2024
Ardelyx (United States)
2016-2023
University of California, Riverside
2022
Amherst College
2022
Bernstein Center for Computational Neuroscience Tübingen
2022
Research Experiences for Undergraduates
2022
The King's College
2022
Sorbonne Université
2012-2021
Pitié-Salpêtrière Hospital
2010-2021
Although electrical alternans (alternating amplitude from beat to on the electrocardiogram) has been associated with ventricular arrhythmias in many clinical settings, its physiologic importance and prognostic implications remain unknown.To test hypothesis that is a marker of vulnerability arrhythmias, we developed technique detect subtle alternation morphologic features electrocardiogram (which would not be detectable by visual inspection electrocardiogram). In group 83 patients referred...
Background —Although T-wave alternans has been closely associated with vulnerability to ventricular arrhythmias, the cellular processes underlying and their role, if any, in mechanism of reentry remain unclear. Methods Results —T-wave on surface ECG was elicited 8 Langendorff-perfused guinea pig hearts during fixed-rate pacing while action potentials were recorded simultaneously from 128 epicardial sites voltage-sensitive dyes. Alternans repolarization phase potential observed above a...
D espite the significant decline in coronary artery disease (CAD) mortality second half of 20th century, 1 sudden cardiac death (SCD) continues to claim 250 000 300 US lives annually. 24][5][6] Because absence emergency medical response systems most world regions, worldwide estimates are currently not available. 7However, even presence advanced first responder for resuscitation out-of-hospital arrest, overall survival rate a recent North American analysis was 4.6%. 8SCD can manifest as...
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...
Background — Specific ion channel mutations underlie the congenital long-QT syndrome (LQTS). However, mechanisms by which dysfunction at molecular level translates into functional electrical instability leading to torsade de pointes (TdP) in LQTS are poorly understood. Methods and Results The cellular basis of TdP was investigated using a novel approach transmural optical imaging canine wedge preparation (n=14). spatial organization repolarization arrhythmogenesis were determined surrogate...
Although expression of numerous ion channels is altered in heart failure (HF), mechanisms by which dysfunction at the ionic and molecular levels lead to ventricular tachyarrhythmias HF are unknown. Previously, we found that transmural heterogeneities repolarization play a critical role genesis polymorphic tachycardia (PVT) when QT interval was prolonged LQT2. Because also HF, hypothesized mechanism PVT HF. Optical action potentials were measured simultaneously from cells spanning entire wall...
T-wave alternans, a powerful marker of arrhythmic events, results from alternation in action potential duration (APD). The underlying cellular mechanism APD alternans is unknown but has been attributed to either intracellular calcium (Ca 2+ ) cycling or membrane ionic currents, manifested by steep slope restitution. To address these mechanisms, high-resolution optical mapping techniques were used measure potentials and Ca transients simultaneously hundreds epicardial sites the guinea pig...
Recently, we found that repolarization heterogeneities between subepicardial and midmyocardial cells can form a substrate for reentrant ventricular arrhythmias in failing myocardium. We hypothesized the mechanism responsible maintaining transmural action potential duration heart failure is related to intercellular uncoupling from downregulation of cardiac gap junction protein connexin43 (Cx43). With use canine model pacing-induced failure, left ventricles were sectioned expose surface (n =...
We have found that women with polycystic ovary syndrome (PCOS) decreased sensitivity and responsiveness to insulin. The present study was performed determine whether this impaired insulin associated diminished GLUT-4 glucose transporter content in adipocytes. Insulin-stimulated transport abundance were measured abdominal adipocytes from obese (n = 9) lean 7) PCOS as well 8) control matched for age weight. No woman had tolerance. maximal insulin-stimulated increment adipocyte independently by...
Unique Properties of Optical Action Potentials. Introduction : mapping with voltage‐sensitive dyes has made it possible to record cardiac action potentials high spatial resolution that is unattainable by conventional techniques. Optically recorded signals possess distinct properties differ importantly from electrograms extracellular electrodes or microelectrode Despite the growing application optical electrophysiology, relatively little quantitative information available regarding...
Several lines of evidence have suggested that maintenance atrial fibrillation (AF) depends on reentrant mechanisms. Maintenance reentry necessitates a sufficiently short refractory period and/or delayed conduction, and AF has been associated with both alterations. Fibrosis, cellular dysfunction, gap junction protein alterations occur in cause conduction delay. We performed this study to test the hypothesis overexpression would improve prevent AF.Thirty Yorkshire swine were randomized into 2...
Abstract —Previously, using an animal model of T-wave alternans in structurally normal myocardium, we demonstrated that repolarization can alternate with opposite phase between neighboring myocytes (ie, discordant alternans), causing spatial dispersions form the substrate for functional block and reentrant ventricular fibrillation (VF). However, mechanisms responsible cellular its electrocardiographic manifestation alternans) patients structural heart disease are unknown. We hypothesize...
Abnormal calcium release from sarcoplasmic reticulum (SR) is considered an important trigger of atrial fibrillation (AF). Whereas increased Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity has been proposed to contribute SR leak and AF induction, downstream targets CaMKII remain controversial. To test the hypothesis that inhibition CaMKII-phosphorylated type-2 ryanodine receptors (RyR2) prevents initiation in FKBP12.6-deficient (-/-) mice. Mice lacking RyR2-stabilizing subunit...
Recent evidence suggests that ion channels governing the response of action potential duration (APD) to a premature stimulus (ie, APD restitution) are heterogeneously dispersed throughout heart. However, because limitations conventional electrophysiological recording techniques, effects restitution in single cells on ventricular repolarization at level intact heart poorly understood. Using high-resolution optical mapping with voltage-sensitive dyes, we measured kinetics 128 simultaneous...
Background Although the relationship between cardiac wavelength (λ) and path length importantly determines stability of reentrant arrhythmias, physiological determinants λ are poorly understood. To investigate cellular mechanisms that control during reentry, we developed an experimental system for continuously monitoring within a circuit with use voltage-sensitive dyes new guinea pig model ventricular tachycardia (VT). Methods Results Action potentials were recorded simultaneously from 128...
Recently we found that electrophysiological (EP) heterogeneities between subepicardial and midmyocardial cells can form a substrate for reentrant ventricular arrhythmias. However, cell-to-cell coupling through gap junctions is expected to attenuate transmural cell types spanning the wall. Because connexin43 (Cx43) principal junction protein, hypothesized EP are in part produced by heterogeneous Cx43 expression across The left ventricles of eight dogs were sectioned expose surface. To...
Abstract Idiopathic generalized epilepsy (IGE) is a common, complex disease with an almost exclusively genetic etiology but variable phenotypes. Clinically, IGE can be divided into different syndromes. Varying lines of evidence point to the involvement several interacting genes in IGE. We performed genome scan 91 families ascertained through proband adolescent‐onset The IGEs included juvenile myoclonic (JME), absence (JAE), and tonic clonic seizures (EGTCS). Our linkage results support...