THE ANTIARRHYTHMIC EFFECT OF FISH OILS IN A MOUSE MODEL OF CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA (CPVT).

DE GIUSTI VC; VENETUCCI L; AVELINO CRUZ JE; LODOLA F; CURCIO A; BONGIANINO R; DENEGRI M; MONTEFORTE N; BLOISE R; NAPOLITANO C; PRIORI SG

Congreso; XX Reunión anual de la International Society for Heart Research (ISHR) Sección Latinoamericana; 2012

THE ANTIARRHYTHMIC EFFECT OF FISH OILS IN A MOUSE MODEL OF CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA (CPVT). De Giusti VC, Venetucci L, Avelino Cruz JE, Lodola F, Curcio A, Bongianino R, Denegri M, Monteforte N, Bloise R, Napolitano C, Priori SG. Fond S. Maugeri I.R.C.C.S. The autosomal dominant form of CPVT, caused by mutations in the ryanodine receptor (RyR2), is characterized by the onset of spontaneous Ca release (SCR) from the sarcoplasmic reticulum that leads to delayed after-depolarizations  (DADs) and arrhythmias  during adrenergic stimulation. We investigated the antiarrhythmic effect of Fish Oils (DHA and EPA) in heterozygous RyR2/RyR2R4496C mice, both in vitro (with patch-clamp) and in vivo (with ECG recordings).  In Vitro preincubation with DHA 10 µM or EPA 20 µM prevented the Isoproterenol-induced SCR delayed and DADs (Iso: 71%; DHA: 10.5%; EPA: 6 %) and triggered activity (TA) (Iso: 68%; DHA: 5.5%; EPA: 0 %). L-type calcium current (ICaL) was reduced (control: -5.4±0.6, n=25; DHA: -3.6±0.5, n=21; EPA: -3.7±0.3, n=15) and the Iso-induced ICaL stimulation was prevented by DHA or EPA (Iso: -9.4±1; n=14, DHA: -2.6±0.5; n=15, EPA: -4.3±0.4; n=15). The SR luminal threshold for calcium leak (53.5±3.2 µM; n=5) was enhanced by DHA (70±4.2 µM; n=4) and EPA (83±6.3 µM; n=11). Consistently, in vivo bidirectional ventricular tachyarrhythmias were prevented by Fish Oils administration. These results suggest that the antiarrhythymic effect of Fish Oils is likely due modulation inhibition of both ICaL and RyR2. Moreover, the in vivo data, allow us to propose Fish Oils as an alternative or additional treatment for the CPVT patients.