title: Acute anti-fibrillating and defibrillating potential of atorvastatin, melatonin, eicosapentaenoic acid and docosahexaenoic acid demonstrated in isolated heart model.
abstract: Cardioprotective compounds such as atorvastatin, melatonin, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibit antiarrhythmic potential in clinical and/or experimental conditions but underlying mechanisms are poorly understood. We have previously shown that protection from ventricular fibrillation (VF) due to prolonged treatment with these compounds was linked with modulation of myocardial connexin-43, which is responsible for myocardial electrical coupling and synchronisation. To elucidate further the antiarrhythmic potential of atorvastatin, melatonin, EPA and DHA we aimed to explore their acute anti-fibrillating effects and defibrillating efficacy. Experiments were conducted on isolated perfused heart preparation of adult male and female hypertriglyceridemic (HTG) rats when using atorvastatin, EPA and DHA, while melatonin was examined in hearts of old male and female guinea pigs. VF inducibility was tested in hearts pre-treated for 10 min with atorvastatin, EPA or DHA (15 μmol) or melatonin (50 μmol) and compared with non-pre-treated hearts. Sustained VF was induced in all untreated HTG rat hearts. In contrast, its incidence was reduced to 30% and 60% by atorvastatin, 70% and 75% by EPA, 60% and 60% by DHA in male or female rat hearts respectively. Moreover, bolus (150 μmol) of EPA and DHA administered directly to the fibrillating heart restored sinus rhythm in 6 of 6 hearts and atorvastatin in 4 of 6 hearts. Threshold to induce sustained VF was 21.7 ± 3.8 mA in male and 38.3 ± 2.9 mA in female guinea pig hearts. However, sustained VF was not possible to induce even by the strongest (50 mA) stimulus in the heart pre-treated with melatonin regardless the sex. In conclusion, atorvastatin, melatonin, EPA and DHA exhibit clear cut acute anti-fibrillating efficacy. Findings challenge to investigate expression of connexin-43, especially its phosphorylated status associated with connexin channel function, in acute conditions.
authors.affiliation: Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia. narcisa.tribulova@savba.sk.
authors.forename: T
authors.initials: T
authors.lastname: Benova
authors.forename: V
authors.initials: V
authors.lastname: Knezl
authors.forename: C
authors.initials: C
authors.lastname: Viczenczova
authors.forename: B S
authors.initials: BS
authors.lastname: Bacova
authors.forename: J
authors.initials: J
authors.lastname: Radosinska
authors.forename: N
authors.initials: N
authors.lastname: Tribulova
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000069059:Atorvastatin / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D006937:Hypercholesterolemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D000067268:Isolated Heart Preparation; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000889:Anti-Arrhythmia Agents; D004281:Docosahexaenoic Acids; D000069059:Atorvastatin; D015118:Eicosapentaenoic Acid; D008550:Melatonin