The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Arthur A.m. Wilde - One of the best experts on this subject based on the ideXlab platform.
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postrepolarization refractoriness in acute ischemia and after antiarrhythmic drug administration action potential duration is not always an index of the refractory period
Heart Rhythm, 2012Co-Authors: Ruben Coronel, Arthur A.m. Wilde, Michiel J Janse, Tobias Opthof, Peter TaggartAbstract:Action potential duration is widely used as a measure of refractory period in ischemia. Although the end of repolarization closely corresponds to the end of refractoriness in the well-perfused, well-oxygenated myocardium, it is no longer true for the ischemic myocardium, in which the recovery of excitability lags behind full repolarization. The purpose the study was to review this phenomenon of postrepolarization refractoriness during ischemia and after application of various antiarrhythmic drugs. The findings showed that although postrepolarization refractoriness is profoundly proarrhythmic during ischemia, it may protect the heart from reentrant arrhythmias in the absence of Depolarization of the resting membrane. An increase in postrepolarization refractoriness induced by sodium-channel–blocking drugs may exert an antifibrillatory action.
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the pathophysiological mechanism underlying brugada syndrome Depolarization versus repolarization
Journal of Molecular and Cellular Cardiology, 2010Co-Authors: Arthur A.m. Wilde, Jeffrey M Fish, Jose M Di Diego, Sami Viskin, Pieter G Postema, Hiroshi Morita, Charles AntzelevitchAbstract:This Point/Counterpoint presents a scholarly debate of the mechanisms underlying the electrocardiographic and arrhythmic manifestations of Brugada syndrome (BrS), exploring in detail the available evidence in support of the repolarization vs. Depolarization hypothesis.
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local Depolarization abnormalities are the dominant pathophysiologic mechanism for type 1 electrocardiogram in brugada syndrome a study of electrocardiograms vectorcardiograms and body surface potential maps during ajmaline provocation
Journal of the American College of Cardiology, 2010Co-Authors: Pieter G Postema, Gerard Van Herpen, Nan Van Geloven, Jan A Kors, Andre C Linnenbank, Jacques M T De Bakker, Pascal F.h.m. Van Dessel, Arthur A.m. WildeAbstract:Objectives We sought to obtain new insights into the pathophysiologic basis of Brugada syndrome (BrS) by studying changes in various electrocardiographic Depolarization and/or repolarization variables that occurred with the development of the signature type 1 BrS electrocardiogram (ECG) during ajmaline provocation testing. Background BrS is associated with sudden cardiac death. Its pathophysiologic basis, although unresolved, is believed to reside in abnormal cardiac Depolarization or abnormal repolarization. Methods Ajmaline provocation was performed in 269 patients suspected of having BrS with simultaneous recording of ECGs, vectorcardiograms, and 62-lead body surface potential maps. Results A type 1 ECG was elicited in 91 patients (BrS patients), 162 patients had a negative test result (controls), and 16 patients had an abnormal test result. Depolarization abnormalities were more prominent in BrS patients and were mapped to the right ventricle (RV) by longer right precordial filtered QRS complex durations (142 ± 23 ms vs. 125 ± 14 ms, p peak -T end interval (143 ± 36 ms vs. 138 ± 25 ms, p = NS), and similar T peak -T end dispersion (47 ± 37 ms vs. 45 ± 27 ms, p = NS). Conclusions The type 1 BrS ECG is characterized predominantly by localized Depolarization abnormalities, notably (terminal) conduction delay in the RV, as assessed with complementary noninvasive electrocardiographic techniques. We could not define a separate role for repolarization abnormalities but suggest that the typical signs of repolarization derangements seen on the ECG are secondary to these Depolarization abnormalities.
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pathophysiological mechanisms of brugada syndrome Depolarization disorder repolarization disorder or more
Cardiovascular Research, 2005Co-Authors: Paola G Meregalli, Arthur A.m. WildeAbstract:After its recognition as a distinct clinical entity, Brugada syndrome is increasingly recognized worldwide as an important cause of sudden cardiac death. Brugada syndrome exhibits autosomal dominant inheritance with SCN5A, which encodes the cardiac sodium channel, as the only gene with a proven involvement in 20–30% of patients. Its signature feature is ST segment elevation in right precordial ECG leads and predisposition to malignant ventricular tachyarrhythmias. The pathophysiological mechanism of ST elevation and ventricular tachyarrhythmia, two phenomena strongly related, is controversial. Here, we review clinical and experimental studies as they provide evidence to support or disprove the two hypotheses on the mechanism of Brugada syndrome that currently receive the widest support: (1) nonuniform abbreviation of right ventricular epicardial action potentials (“repolarization disorder”), (2) conduction delay in the right ventricular outflow tract (“Depolarization disorder”). We also propose a schematic representation of the Depolarization disorder hypothesis. Moreover, we review recent evidence to suggest that other derangements may also contribute to the pathophysiology of Brugada syndrome, in particular, right ventricular structural derangements. In reviewing these studies, we conclude that, similar to most diseases, it is likely that Brugada syndrome is not fully explained by one single mechanism. Rather than adhering to the notion that Brugada syndrome is a monofactorial disease, we should aim for clarification of the contribution of various pathophysiological mechanisms in individual Brugada syndrome patients and tailor therapy considering each of these mechanisms.
Toshio Narahashi - One of the best experts on this subject based on the ideXlab platform.
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differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin sensitive and tetrodotoxin resistant sodium channels
Journal of Pharmacology and Experimental Therapeutics, 1994Co-Authors: Hideharu Tatebayashi, Toshio NarahashiAbstract:Rat dorsal root ganglion neurons are endowed with tetrodotoxin-sensitive(TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels. The pyrethroid insecticides, which are known to keep sodium channels open for a prolonged period of time, cause differential effects on the two types of sodium channels. The whole-cell patch clamp experiments were performed with rat dorsal root ganglion neurons in primary culture. In TTX-S sodium channels, the slow sodium current during step Depolarization was increased somewhat by tetramethrin, and a tail sodium current with a slowly rising and falling phase appeared upon repolarization. The tail current developed even after the sodium current during Depolarization had subsided. In TTX-R sodium channels, the slow sodium current during step Depolarization was increased markedly by tetramethrin, and upon repolarization a large instantaneous tail current was generated and decayed slowly. The steady-state sodium channel inactivation curve was shifted by tetramethrin in the hyperpolarizing direction in both TTX-S and TTX-R channels. The sodium conductance-voltage curve also was shifted by tetramethrin in the hyperpolarizing direction in both TTX-S and TTX-R channels, and the latter was affected more strongly than the former. At a concentration of 10 microM, the highest concentration tested, tetramethrin modified only 12% of the TTX-S sodium channels, whereas the modification was as high as 81% in the TTX-R. Even at 10 nM, 1.3% of TTX-R sodium channels were modified; this accounts for the high potency of tetramethrin as an insecticide.(ABSTRACT TRUNCATED AT 250 WORDS)
Pieter G Postema - One of the best experts on this subject based on the ideXlab platform.
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the pathophysiological mechanism underlying brugada syndrome Depolarization versus repolarization
Journal of Molecular and Cellular Cardiology, 2010Co-Authors: Arthur A.m. Wilde, Jeffrey M Fish, Jose M Di Diego, Sami Viskin, Pieter G Postema, Hiroshi Morita, Charles AntzelevitchAbstract:This Point/Counterpoint presents a scholarly debate of the mechanisms underlying the electrocardiographic and arrhythmic manifestations of Brugada syndrome (BrS), exploring in detail the available evidence in support of the repolarization vs. Depolarization hypothesis.
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local Depolarization abnormalities are the dominant pathophysiologic mechanism for type 1 electrocardiogram in brugada syndrome a study of electrocardiograms vectorcardiograms and body surface potential maps during ajmaline provocation
Journal of the American College of Cardiology, 2010Co-Authors: Pieter G Postema, Gerard Van Herpen, Nan Van Geloven, Jan A Kors, Andre C Linnenbank, Jacques M T De Bakker, Pascal F.h.m. Van Dessel, Arthur A.m. WildeAbstract:Objectives We sought to obtain new insights into the pathophysiologic basis of Brugada syndrome (BrS) by studying changes in various electrocardiographic Depolarization and/or repolarization variables that occurred with the development of the signature type 1 BrS electrocardiogram (ECG) during ajmaline provocation testing. Background BrS is associated with sudden cardiac death. Its pathophysiologic basis, although unresolved, is believed to reside in abnormal cardiac Depolarization or abnormal repolarization. Methods Ajmaline provocation was performed in 269 patients suspected of having BrS with simultaneous recording of ECGs, vectorcardiograms, and 62-lead body surface potential maps. Results A type 1 ECG was elicited in 91 patients (BrS patients), 162 patients had a negative test result (controls), and 16 patients had an abnormal test result. Depolarization abnormalities were more prominent in BrS patients and were mapped to the right ventricle (RV) by longer right precordial filtered QRS complex durations (142 ± 23 ms vs. 125 ± 14 ms, p peak -T end interval (143 ± 36 ms vs. 138 ± 25 ms, p = NS), and similar T peak -T end dispersion (47 ± 37 ms vs. 45 ± 27 ms, p = NS). Conclusions The type 1 BrS ECG is characterized predominantly by localized Depolarization abnormalities, notably (terminal) conduction delay in the RV, as assessed with complementary noninvasive electrocardiographic techniques. We could not define a separate role for repolarization abnormalities but suggest that the typical signs of repolarization derangements seen on the ECG are secondary to these Depolarization abnormalities.
Thomas Pambrun - One of the best experts on this subject based on the ideXlab platform.
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Depolarization versus repolarization abnormality underlying inferolateral j wave syndromes new concepts in sudden cardiac death with apparently normal hearts
Heart Rhythm, 2019Co-Authors: Michel Haissaguerre, Koonlawee Nademanee, Meleze Hocini, Ghassen Cheniti, Josselin Duchateau, Antonio Frontera, Frederic Sacher, Nicolas Derval, Arnaud Denis, Thomas PambrunAbstract:Early repolarization indicates a distinct electrocardiographic phenotype affecting the junction between the QRS complex and the ST segment in inferolateral leads (inferolateral J-wave syndromes). It has been considered a benign electrocardiographic variant for decades, but recent clinical studies have demonstrated its arrhythmogenicity in a small subset, supported by experimental studies showing transmural dispersion of repolarization. Here we review the current knowledge and the issues of risk stratification that limit clinical management. In addition, we report on new mapping data of patients refractory to pharmacologic treatment using high-density electrogram mapping at the time of inscription of J wave. These data demonstrate that distinct substrates, delayed Depolarization, and abnormal early repolarization underlie inferolateral J-wave syndromes, with significant implications. Finally, based on these data, we propose a new simplified mechanistic classification of sudden cardiac deaths without apparent structural heart disease.
Mitchell Goldfarb - One of the best experts on this subject based on the ideXlab platform.
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Voltage-gated sodium channel-associated proteins and alternative mechanisms of inactivation and block
Cellular and Molecular Life Sciences, 2012Co-Authors: Mitchell GoldfarbAbstract:Voltage-gated sodium channels mediate inward current of action potentials upon membrane Depolarization of excitable cells. The initial transient sodium current is restricted to milliseconds through three distinct channel-inactivating and blocking mechanisms. All pore-forming alpha subunits of sodium channels possess structural elements mediating fast inactivation upon Depolarization and recovery within milliseconds upon membrane repolarization. Accessory subunits modulate fast inactivation dynamics, but these proteins can also limit current by contributing distinct inactivation and blocking particles. A-type isoforms of fibroblast growth factor homologous factors (FHFs) bear a particle that induces long-term channel inactivation, while sodium channel subunit Navβ4 employs a blocking particle that rapidly dissociates upon membrane repolarization to generate resurgent current. Despite their different physiological functions, the FHF and Navβ4 particles have similarity in amino acid composition and mechanisms for docking within sodium channels. The three competing channel-inactivating and blocking processes functionally interact to regulate a neuron’s intrinsic excitability.
