INITIATION, SUSTAINING AND TERMINATION OF VENTRICULAR FIBRILLATION DEPEND ON INTRACELLULAR CALCIUM CONCENTRATIONRN

The aim of the study was 1) to monitor myocardial [Ca2+]i levels during the development and persistence of ventricular fibrillation (VF) as well as during its conversion to sinus rhythm. 2) to detect cell-to-cell gap junction coupling alterations prior occurrence and immediately after termination of VF when sinus rhythm appeared. 3) to analyse as whether susceptibility of the heart to VF is associated with the activity of main myocardial Ca2+ cycling system, i.e. SERCA2a . Results showed that elevation of diastolic [Ca2+]i reached 180% of baseline level prior occurrence of acute hypokalemia-induced VF and it was associated with an impairment of gap junction mediated cell-to-cell coupling. VF itself resulted in further [Ca2+]i increase that aggravated cell-to-cell coupling  injury and synchronisation. In contrast, VF conversion to sinus rhythm was dependent on the restoration of basal [Ca2+]i levels (facilitated by antiarrhythmic drug stobadine) and it was linked with apparent abolishment of cell-to-cell coupling disorders. SERCA2a activity was significantly decreased in old guinea pig hearts that were susceptible to VF in comparison to young hearts that were rather resistant. The latter developed Ca2+ overload-induced cardiomyocyte injury including marked impairment of cell-to cell coupling only after long-term repetitive electrical stimulations different to old guinea pig hearts that developed these changes after a few electrical stimuli. Collectively these findings indicate that modulation of Ca2+ handling systems may be a critical in development, sustaining and termination of VF. It appears that prevention or abolishment of Ca2+ overload in diseased heart by enhancement of sarcoplamsic reticulum SERCA2a activity can protect against malignant arrhythmias.