title: The protective effect of class III antiarrhythmic agents against calcium overload in cultured myocytes.
abstract: Calcium ions have been implicated in the mechanisms of ventricular arrhythmias. Impairment of intercellular coupling by calcium overload is considered to facilitate ventricular fibrillation (VF) and to sup-press its self termination. According to our hypothesis, any compound that decreases intracellular calcium concentration [Ca2+]i during VF can serve as defibrillating drug. In this study, we examined the effect of d-sotalol and tedisamil on calcium overload in cultured, spontaneously beating rat cardiomyocytes. The changes of [Ca2+]i were measured by indo-1 method and the intercellular synchronization by image analysis. The results showed that increase in [Ca2+]o from 1.9 mM to 3.9 mM increased [Ca2+]i from 100 nM to 320 nM and transformed the synchronized cell movement to an asynchronous one. Administration of 5 x 10(-6) M d-sotalol or 10(-6) M tedisamil, decreased the [Ca2+]i to its basic level and restored the synchronized activity. In summary: Our results showed that increase in [Ca2+]i known to cause inhibition of intercellular coupling, that could lead to arrhythmia and fibrillation while d-sotalol or tedisamil prevented this effect. These results support our hypothesis, that class III antiarrhythmic compounds with positive inotropic effect, increase intercellular synchronization, by decreasing free [Ca2+]i, most probably by increasing the Ca2+ uptake by the sarcoplasmic reticulum, and therefore act as a defibrillating compound.
authors.affiliation: Department of Physiology, Tel Aviv Medical School, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Manoach
authors.forename: D
authors.initials: D
authors.lastname: Varon
authors.forename: A
authors.initials: A
authors.lastname: Shainberg
authors.forename: T
authors.initials: T
authors.lastname: Zinman
authors.forename: A
authors.initials: A
authors.lastname: Isaack
authors.forename: I H
authors.initials: IH
authors.lastname: Rutman
authors.forename: D
authors.initials: D
authors.lastname: Kaplan
authors.forename: N
authors.initials: N
authors.lastname: Tribulova
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002118:Calcium / Q000009:adverse effects / Q000378:metabolism*; D002478:Cells, Cultured; D003521:Cyclopropanes / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013015:Sotalol / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003521:Cyclopropanes; C059921:tedisamil; D013015:Sotalol; D002118:Calcium