Ventricular fibrillation-induced intracellular Ca2+ overload causes failed electrical defibrillation and post-shock reinitiation of fibrillation.

Despite high efficacy, electrical defibrillation shocks can fail or ventricular fibrillation (VF) is reinitiated after the application of the initial shock. The goal of this study was to determine whether [Ca2+]i overload, induced by VF itself, can cause failed electrical defibrillation and post-shock reinitiation of VF. For this purpose, we simultaneously measured [Ca2+]i transients (assessed by indo-1 fluorescence) and defibrillation energies (assessed by a modified implantable cardioverter defibrillator) in intact perfused rat hearts during pacing-induced sustained VF (10 min) in the absence of ischemia. We found that increasing [Ca2+]i during VF (by increasing [Ca2+]o from 3 to 6 mM) increased the defibrillation threshold (DFT) from 1.9 +/- 0.6 to 3.5 +/- 0.5 J/g (P<0.05) and also increased the total defibrillation energy (TDE) required for stabilization of sinus rhythm from 15.6 +/- 7.7 to 48.6 +/- 7.42 J/g (P<0.05). In addition, both DFT and TDE correlated linearly with [Ca2+]i (r=0.69 and 0.83, P<0.05). Furthermore, shortening the duration of VF from 10 to 1.5 min tended to limit [Ca2+]i overload and decreased TDE. Finally, all successful defibrillation shocks led to a sudden reduction of VF-induced [Ca2+]i overload (-115 +/- 3%). In contrast, failed shocks did not alter [Ca2+]i. Incomplete reduction of [Ca2+]i overload after initially successful shocks were often followed by synchronized spontaneous [Ca2+]i oscillations and subsequent reinitiation of VF. In conclusion, the present study showed for the first time that VF-induced [Ca2+]i overload can cause failed electrical defibrillation and post-shock reinitiation of VF. Because VF inevitably causes [Ca2+]i overload, this finding might be a crucial mechanism of failed defibrillation and spontaneous reinitiation of VF.