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001-es BibID:BIBFORM082084
035-os BibID:(WoS)000582745400009 (Scopus)85075368709 (PubMed)31726065
Első szerző:Nánási Péter Pál (élettanász)
Cím:Implication of frequency-dependent protocols in antiarrhythmic and proarrhythmic drug testing / Péter P. Nánási, Zoltán Szabó, Kornél Kistamás, Balázs Horváth, László Virág, Norbert Jost, Tamás Bányász, János Almássy, András Varró
Dátum:2020
ISSN:0079-6107
Megjegyzések:It has long been known that the electrophysiological effects of many cardioactive drugs strongly depend on the rate dependent frequency. This was recognized first for class I antiarrhythmic agents: their Vmax suppressive effect was attenuated at long cycle lengths. Later many Ca2+ channel blockers were also found to follow such kinetics. The explanation was provided by the modulated and the guarded receptor theories. Regarding the duration of cardiac action potentials (APD) an opposite frequency-dependence was observed, i.e. the drug-induced changes in APD were proportional with the cycle length of stimulation, therefore it was referred as "reverse rate-dependency". The beat-to-beat, or short term variability of APD (SV) has been recognized as an important proarrhythmic mechanism, its magnitude can be used as an arrhythmia predictor. SV is modulated by several cardioactive agents, however, these drugs modify also APD itself. In order to clear the drug-specific effects on SV from the concomitant unspecific APD-change related ones, the term of "relative variability" was introduced. Relative variability is increased by ion channel blockers that decrease the negative feedback control of APD (i.e. blockers of ICa, IKr and IKs) and also by elevation of cytosolic Ca2+. Cardiac arrhythmias are also often categorized according to the characteristic heart rate (tachy- and bradyarrhythmias). Tachycardia is proarrhythmic primarily due to the concomitant Ca2+ overload causing delayed afterdepolarizations. Early afterdepolarizations (EADs) are complications of the bradycardic heart. What is common in the reverse rate-dependent nature of drug action on APD, increased SV and EAD incidence associated with bradycardia.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Cardiac myocytes
Cardiac arrhythmias
Action potential duration
Cardiac ion currents
Rate-dependent actions
Reverse rate-dependency
Short term variability
Triggered activity
Megjelenés:Progress In Biophysics & Molecular Biology. - 157 (2020), p. 76-83. -
További szerzők:Szabó Zoltán (1973-) (belgyógyász, kardiológus) Kistamás Kornél (1986-) (biológus) Horváth Balázs (1981-) (élettanász) Virág László (élettanász Szeged) Jost Norbert Bányász Tamás (1960-) (élettanász) Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító) Varró András (1954-) (farmakológus, klinikai farmakológus)
Pályázati támogatás:NKFIH K115397
egyéb
NKFIH K-119992
egyéb
GINOP-2.3.2.-15-2016-00040
GINOP
20391-3/2018/FEKUSTRAT
egyéb
EFOP-3.6.2-16-2017-00006
EFOP
ED_18-1-2019-0028
egyéb
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