PS 01-10] ANTIARRHYTHMIC EFFECT OF ACUTE ADMINISTRATION OF ATORVASTATIN AND OMEGA-3 FATTY ACIDS DEMONSTRATED IN PERFUSED HEART OF MALE AND FEMALE HEREDITARY HYPERTRIGLYCERIDEMIC RATS SUFFERING FROM HYPERTENSION

Abstract

Objective: It is known that chronic treatment with statins and omega-3 FA (omega-3) exhibit cardioprotective and antiarrhythmic effects in clinical practice. We have previously shown that prolonged treatment of hereditary hypertriglyceridemic (HTG) rats suffering from hypertension with these compounds reduced the incidence of ventricular fibrillation (VF) partially due to modulation of cardiac electrical coupling protein connexin-43. To elucidate further underlying antiarrhythmic mechanisms, this study was aimed to explore whether these compounds exert acute antiarrhythmic effects. Design and Method: Experiments were conducted on adult, male and female HTG rats known to be much prone to VF than healthy rats. The hearts were excised from anesthetized rats and perfused with oxygenated Krebs-Henseleit solution at constant flow. VF inducibility was tested in control hearts and compared with the hearts, which were pre-treated during 10 min prior electrical stimulation with either atorvastatin, eicosapentanoic acid (EPA) or docosahexanoic acid (DHA) in concentration 1.5, 7, 15 μmol. Results: Sustained VF was induced in all HTG rat hearts without treatment. In contrast, the hearts subjected to atorvastatin, EPA and DHA were less susceptible to inducible VF and incidence of sustained VF was reduced to 30%, 70% and 80% in male, and to 60%, 75% and 60% in female rats. Atorvastatin suppressed VF inducibility in male rats already in concentration 1.5 μmol, while EPA and DHA were efficient at higher, 7 and 15 μmol. Moreover, bolus (150 μmol) of EPA and DHA administered directly to fibrillating hearts terminated VF in 6 out of 6 hearts and atorvastatin in 3 out of 6 hearts. Conclusions: Atorvastatin likewise EPA and DHA exhibit clear antifibrillating and defibrillating efficacy when acutely applied. Findings point out the importance of pleiotropic effects of statins and diet-related approaches in prevention of malignant arrhythmias.