The role of Purkinje-myocardial coupling during ventricular arrhythmia: a modeling study.

The Purkinje system is the fast conduction network of the heart which couples to the myocardium at discrete sites called Purkinje-Myocyte Junctions (PMJs). However, the distribution and number of PMJs remains elusive, as does whether a particular PMJ is functional. We hypothesized that the Purkinje system plays a role during reentry and that the number of functional PMJs affect reentry dynamics. We used a computer finite element model of rabbit ventricles in which we varied the number of PMJs. Sustained, complex reentry was induced by applying an electric shock and the role of the Purkinje system in maintaining the arrhythmia was assessed by analyzing phase singularities, frequency of activation, and bidirectional propagation at PMJs. For larger junctional resistances, increasing PMJ density increased the mean firing rate in the Purkinje system, the percentage of successful retrograde conduction at PMJs, and the incidence of wave break on the epicardium. However, the mean firing of the ventricles was not affected. Furthermore, increasing PMJ density above 13/[Formula: see text] did not alter reentry dynamics. For lower junctional resistances, the trend was not as clear. We conclude that Purkinje system topology affects reentry dynamics and conditions which alter PMJ density can alter reentry dynamics.

Dantrolene improves survival after ventricular fibrillation by mitigating impaired calcium handling in animal models.

BACKGROUND: Resistant ventricular fibrillation, refibrillation. and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VF. METHODS AND RESULTS: VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls (P=0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21 ± 6 s versus 181 ± 57 s in controls, P=0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P=0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts (P=0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 µmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024 ± 0.013 versus 0.12 ± 0.02 arbitrary unit [200-ms cycle length], P=0.001). CONCLUSIONS: Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling.