Current concepts on ventricular fibrillation: a vicious circle of cardiomyocyte calcium overload in the initiation, maintenance, and termination of ventricular fibrillation

Abstract

Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF) are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocardial ischemia, or heart failure. On the other hand, VF itself directly and rapidly causes progressive myocyte Ca2+ overload that maintains VF and renders termination of VF increasingly difficult. Accordingly, energy levels for successful electrical defibrillation (defibrillation thresholds) increase as both VF and Ca2+ overload progress. Furthermore, VF-induced myocyte Ca2+ overload can promote re-induction of VF after defibrillation and/or postfibrillatory myocardial dysfunction (postresuscitation stunning) due to reduced myofilament Ca2+ responsiveness. The probability of these adverse events is best reduced by early detection and rapid termination of VF to prevent or limit Ca2+ overload. Early additional therapy targeting transsarcolemmal Ca2+ entry, particularly during the first 2 min of VF, may partially prevent myocyte Ca2+ overload and thus, increase the likelihood of successful defibrillation as well as prevent postfibrillatory myocardial dysfunction.

Figure 1

Original tracings of indo-1 fluorescence ratio transients (F400/F510), an index of myocyte Ca²⁺, in intact perfused rat hearts after the initiation of sustained VF (induced by 1-min rapid pacing at 20 Hz) and after electrical defibrillation. Note that myocyte Ca²⁺ rises rapidly and steeply upon VF to decrease again upon defibrillation.

Figure 2

Myocyte Ca²⁺ overload and VF form a vicious circle in which elevated Ca²⁺ can induce VF and conversely, VF promotes Ca²⁺ overload maintaining the arrhythmia. As both VF and Ca²⁺ overload progress, energy levels for successful electrical defibrillation increase (symbolized by spiral). If defibrillation succeeds, VF-induced Ca²⁺ overload may cause postfibrillatory myocardial dysfunction (postresuscitation stunning).