herapeutic hypothermia (TH, 30°C) has decreased intracranial pressure, slowed cerebral metabolic processes, and protected the brain from anoxic injury in animal models and human scenarios. [1][2][3] Recent guidelines also recommend that unconscious adult patients with spontaneous circulation after out-of-hospital ventricular fibrillation (VF) cardiac arrest should be cooled to 32-34°C for 12-24 h. [4][5][6] Although previous studies showed that extreme hypothermia (<29°C) might potentiate the occurrence of lethal ventricular arrhythmia, 7-9 the myocardial substrate properties in the therapeutic range of hypothermia (≥30°C) are not completely understood. Because 30°C is the lowest temperature that has proven to be feasible in clinical practice, 1-3 we chose it to test the ventricular substrate for arrhythmogenesis in the present study.One mechanism for determining the maintenance of VF is its wavefront characteristics during VF. 10,11 Harada et al found that in 2-dimensional rabbit ventricular preparations, TH (30°C) enhanced wavebreaks and regeneration of new spiral waves during VF, facilitating the maintenance of ventricular tachycardia (VT) and VF. 12 While using a clinically appropriate temperature of 32-34°C, they demonstrated that the spiral waves of VT/VF frequently collided and dissipated in favor of self-termination of VT/VF, a different effect from that of TH at 30°C. 12 Whether the wavefront characteristics (ie, wavebreaks) of VF in this 2-dimensional model also occur in 3-dimensional intact hearts at TH (30°C) remains unclear. Cardiac alternans, particularly spatially discordant alternans (SDA), is a key arrhythmogenic factor for ventricular tachyarrhythmia. 13 However, limited information is available regarding cardiac alternans properties during TH (30°C). 14 In this study, using an optical mapping system, we investigated the wavefront characteristics of VF (ie, wavebreaks, spatiotemporal periodicities), cardiac electrophysiological/ alternans properties, and the vulnerability of pacing-induced VF specifically at TH (30°C) in 3-dimensional Langendorffperfused isolated rabbit hearts. We hypothesized that TH (30°C) enhances wavebreaks during VF and S1 pacing, facilitates pacing-induced SDA, and increases the vulnerability of pacing-induced VF. Background: Therapeutic hypothermia (TH, 30°C) protects the brain from hypoxic injury. However, TH may potentiate the occurrence of lethal ventricular fibrillation (VF), although the mechanism remains unclear. The present study explored the hypothesis that TH enhances wavebreaks during VF and S1 pacing, facilitates pacinginduced spatially discordant alternans (SDA), and increases the vulnerability of pacing-induced VF. Methods and Results:Using an optical mapping system, epicardial activations of VF were studied in 7 Langendorff-perfused isolated rabbit hearts at baseline (37°C), TH (30°C), and rewarming (37°C). Action potential duration (APD)/conduction velocity (CV) restitution and APD alternans (n=6 hearts) were determined by S1 pacing at these 3 stages. Duri...

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n the basis of the ESVEM trial, d,l-sotalol has been approved for the treatment of life-threatening ventricular tachycardia (VT) and ventricular fibrillation (VF). 1,2 It has been shown that d,l-sotalol reduces the complexity of epicardial activation patterns and prolonged wavelength (WL) during VF in isolated rabbit hearts. 3 Recently, Pak et al reported that d,l-sotalol at therapeutic doses (≤10 mg/L) effectively terminated VF/VT by flattening the action potential duration restitution (APDR) in isolated swine ventricles. 4 However, the effects of d,l-sotalol at therapeutic concentrations on the wavefront characteristics of VF and the genesis of electrophysiological heterogeneity (such as action potential duration (APD) dispersion and spatial heterogeneity of restitutions) are still not completely understood.We previously demonstrated that 2 types of VF exist in the same isolated rabbit heart. 5 As APDR was flattened by low-dose methoxyverapamil (D600), multiple-wavelet type 1 VF was converted to VT. A further increase of D600 concentration converted VT to a slower (type 2) VF with a stationary or slow drifting mother rotor. During type 2 VF, an anatomical structure (the papillary muscle (PM)), always served as an anchoring site for the mother rotor. 6,7 We hypothesized that d,l-sotalol at therapeutic concentrations, with both its effects of APDR flattening and WL prolongation, would also convert a preexisting type 1 VF into a regular rhythm, finally leading to termination of the ventricular tachyarrhythmia. To test this hypothesis, an optical mapping system was used to record epicardial activation patterns during d,l-sotalol infusion in isolated rabbit hearts. The aims of this study were to determine (1) whether or not acute administration of d,l-sotalol can effectively convert a preexisting VF into VT before its termination, and (2) the wavefront characteristics of VF and the electrophysiological heterogeneity during d,l-sotalol infusion with therapeutic concentrations. MethodsThis research protocol was approved by the Institutional Animal Care and Use Committee of Taichung Veterans General Hospital and followed the guidelines of American (Received June 5, 2008; revised manuscript received July 19, 2008; accepted August 5, 2008; released online November 13, 2008