d,l-Sotalol at Therapeutic Concentrations Facilitates the Occurrence of Long-Lasting Non-Stationary Reentry During Ventricular Fibrillation in Isolated Rabbit Hearts

Abstract

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

Therapeutic Hypothermia (30.DEG.C) Enhances Arrhythmogenic Substrates, Including Spatially Discordant Alternans, and Facilitates Pacing-Induced Ventricular Fibrillation in Isolated Rabbit Hearts

“…21 Construction of APD and CT −1 Restitution Curves Using S1 Pacing Method The method of constructing APD and CT −1 restitution curves has been reported elsewhere. 17,18 Briefly, pixels at the center of the anterior and posterior surfaces of both ventricles (sites a-d, Figure 1A) were selected to determine the APD70 (APD at 70% repolarization). 18 APD restitution (APDR) curves of each heart were plotted with means of APD70 from the 4 sites against different S1 PCLs.…”

“…15,16 A pseudo-ECG was obtained with widely spaced bipoles to determine ventricular rhythm. 17 The signals were digitized by an AxoScope with a sampling rate of 1 kHz. [15][16][17][18][19] Optical Mapping Using a 2-camera optical mapping system, epicardial activations in the anterior and posterior aspects of the hearts were simultaneously mapped.…”

“…17 The signals were digitized by an AxoScope with a sampling rate of 1 kHz. [15][16][17][18][19] Optical Mapping Using a 2-camera optical mapping system, epicardial activations in the anterior and posterior aspects of the hearts were simultaneously mapped. 15,16 The hearts were stained with di-4-ANEPPS, and excited with 4 light-emitting diode modules (wavelength=519±20 nm).…”

Repetitive Endocardial Focal Discharges During Ventricular Fibrillation With Prolonged Global Ischemia in Isolated Rabbit Hearts

“…The pseudo-ECG was used to determine the rhythm of the ventricles. 1,2,4,5,13 Simultaneous Endocardial and Epicardial Mappings With a Two-Camera Optical Mapping System Using a two-camera optical mapping system, as in previous studies, endocardial and epicardial activation patterns during VF were studied at baseline, during no-flow GI (with or without electrical defibrillation) and during reperfusion. 2,4,5 Both the LV endocardium and parts of the epicardium of both ventricles were simultaneously mapped.…”

New epicardial mapping electrode with warming/cooling function for experimental electrophysiology studies

“…The analysis of the effects of these changes on the electrophysiological parameters of the myocardium and on the wavefront dynamics can provide valuable information in relation to the mechanisms for generating or maintaining malignant arrhythmias [1][2][3][4][5].…”