Abstract 8784: Mechanisms of Recurrent Spontaneous Ventricular Fibrillation in a Rabbit Model of Electrical Storm

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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 ( I KATP ) activation underlies the mechanisms of ES. Methods and Results: Intracellular Ca 2+ (Ca i ) 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 (APD 50 ) while lowering [K + ] o during isoproterenol infusion prolonged Ca i transient duration (Ca i TD 50 ). Increased difference between Ca i TD and APD (ΔCa i TD 50 -APD 50 ) 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 ΔCa i TD 50 -APD 50 (Figure A). The focal wavefronts developed wavebreak at sites with large voltage gradient, leading to SVF. Suppression of I Ca,L with nifedipine (10 μ mol/L) reliably prevented ES when given before, but not after, the development of SVF. I KATP blockade with glibenclamide (5 μ mol/L) prolonged post-shock APD 50 and suppressed ES in all ventricles (Figure B). An I Kr 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 I KATP and abbreviated APD 50 . Low [K + ] o increases Ca i TD 50. These two factors synergistically enlarge the postshock ΔCa i TD 50 -APD 50 and induce late phase 3 afterdepolarization, triggered activity, wavebreaks and recurrent SVF (electrical storm). I KATP blockade effectively prolongs post-shock APD 50 and suppresses ES.