Abstract 8784: Mechanisms of Recurrent Spontaneous Ventricular Fibrillation in a Rabbit Model of Electrical Storm
Introduction: Electrical storm (ES) is defined as recurrent spontaneous ventricular fibrillation (SVF) within a short period of time. The mechanism of ES remains unclear.
Objective: To develop a model of ES in normal rabbit ventricles and to test the hypothesis that ATP-sensitive K+ current (IKATP) activation underlies the mechanisms of ES.
Methods and Results: Intracellular Ca2+ (Cai) and membrane voltage were optically mapped in 32 Langendorff-perfused rabbit ventricles. At baseline, no SVF was observed after 5 attempts of the VF-defibrillation episodes. During the post-shock period, isoproterenol (0.3 μ mol/L) heterogeneously shortened 50% recovery of action potential duration (APD50) while lowering [K+]o during isoproterenol infusion prolonged Cai transient duration (CaiTD50). Increased difference between CaiTD and APD (ΔCaiTD50-APD50) lead to late phase 3 early afterdepolarization, triggered activity and SVF. In 11 (69%) of 16 SVF episodes, the VF originated from a focal site with maximal or next to maximal ΔCaiTD50-APD50 (Figure A). The focal wavefronts developed wavebreak at sites with large voltage gradient, leading to SVF. Suppression of ICa,L with nifedipine (10 μ mol/L) reliably prevented ES when given before, but not after, the development of SVF. IKATP blockade with glibenclamide (5 μ mol/L) prolonged post-shock APD50 and suppressed ES in all ventricles (Figure B). An IKr blocker E-4031 (1 μ mol/L) failed to terminate ES. The lactate concentration did not increase after 5 VF episodes.
Conclusions: VF during beta-adrenergic stimulation causes non-ischemic activation of IKATP and abbreviated APD50. Low [K+]o increases CaiTD50. These two factors synergistically enlarge the postshock ΔCaiTD50-APD50 and induce late phase 3 afterdepolarization, triggered activity, wavebreaks and recurrent SVF (electrical storm). IKATP blockade effectively prolongs post-shock APD50 and suppresses ES.
- © 2011 by American Heart Association, Inc.