Role of intramural virtual electrodes in shock-induced activation of left ventricle: Optical measurements from the intact epicardial surface Oleg F. Sharifov, MD, PhD, Vladimir G. Fast, PhD From the Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama. BACKGROUND According to one hypothesized mechanism of de- fibrillation, shocks directly excite the bulk of ventricular myocar- dium in the excitable state due to intramural virtual electrodes; however, this hypothesis has not been examined in intact myo- cardium. OBJECTIVES The purpose of this study was examine the role of intramural virtual electrodes in shock-induced activation of intact left ventricular (LV) tissue. METHODS Twelve isolated porcine LV preparations were stained with a transmembrane potential (V m )-sensitive dye by two meth- ods: (1) surface staining and (2) global staining via coronary perfusion. Shocks (E 0.8 – 48 V/cm, duration = 10 ms) were applied across the wall from epicardium to endocardium during diastole via transparent electrodes. Shock-induced V m responses were measured optically from the intact epicardial surface after surface staining and global staining. RESULTS Surface-staining recordings demonstrated different V m responses to cathodal and anodal shocks. Whereas cathodal shocks caused depolarization and rapid activation of the epicardial sur- face, anodal shocks induced hyperpolarization and delayed surface activation. In contrast, global-staining V m responses to cathodal and anodal shocks were qualitatively similar. Both responses were characterized by activation with small latency and rapid propaga- tion. Weak shocks of both polarities induced monotonic action potential upstrokes; stronger shocks induced nonmonotonic up- strokes with two rising phases at shock onset and end. Such features of global-staining V m responses as make activation of the epicardium by anodal shocks and the nonmonotonic action poten- tial upstrokes can be explained by the presence of subepicardial intramural virtual electrodes. CONCLUSION These data suggest that shocks induce intramural virtual electrodes that directly excite LV tissue and account for the shape of optical V m responses recorded from the epicardial surface. KEYWORDS Arrhythmia; Defibrillation; Optical mapping; Ventri- cles; Electrical shock (Heart Rhythm 2006;3:1063–1073) © 2006 Heart Rhythm Society. All rights reserved. Introduction Although application of electrical shocks remains the only reliable method for terminating life-threatening cardiac ar- rhythmias such as ventricular fibrillation, the mechanism of defibrillation is not completely understood. Early studies hy- pothesized that shocks directly excite a critical mass of ven- tricular myocardium, thereby blocking propagation of reen- trant waves or wavelets and stopping the fibrillation. 1,2 Later studies showed that a shock field strength higher than the excitation threshold must be achieved in 90% of the myo- cardium in order to excite relatively refractory tissue and pre- vent formation of new reentrant waves. 3,4 In addition to tissue excitation, shocks can cause prolongation of the action poten- tial (AP) and synchronization of repolarization, which may facilitate defibrillation. 5–10 Besides depolarization, shocks also produce hyperpolarization in some regions of the heart. De- pending on the shock strength, delayed excitation of hyperpo- larized tissue may cause formation of new reentrant waves and defibrillation failure. 10 –13 Another factor that may play an important role in defibrillation is electroporation. 14 –16 Whereas shocks may cause various effects in the heart and defibrillation mechanism may be multifactorial, direct and rapid excitation of a large tissue mass appears to be an essential element of the defibrillation mechanism. However, how shocks stimulate the intramural myocardium in the left ventricle (LV) remains un- clear. There are two main concepts of shock-induced stimulation of the intramural LV. From the position of the classic cable theory, 17 which considers the myocardium to be a continuum, the shock depolarizes the surface of the LV wall facing the cathode and hyperpolarizes the surface facing the anode. The magnitude of transmembrane potential (V m ) displacement de- cays exponentially with distance from either surface and be- comes negligible after several electrotonic space constants. In this model, the majority of myocardium is not affected by a shock and is activated by propagation of an AP. 18 The second concept suggests that electrical shocks produce intramural vir- tual electrodes in the bulk of the LV wall. 19,20 Theoretical studies suggested that intramural virtual electrodes can be formed due to resistive discontinuities in the ventricular tissue structure 19 –21 as a result of changing fiber orientation 22,23 or nonuniformity in the shock electrical field. 24,25 Experimen- tally, optical mapping studies demonstrated formation of vir- This work is supported by National Institutes of Health Grants HL67748 and HL67961. Address reprint requests and correspondence: Dr. Oleg F. Sharifov, University of Alabama at Birmingham, 1670 University Boulevard, VH B133, Birmingham, Alabama 35294. E-mail address: sharifov@crml.uab.edu. (Received December 13, 2005; accepted May 12, 2006) 1547-5271/$ -see front matter © 2006 Heart Rhythm Society. All rights reserved. doi:10.1016/j.hrthm.2006.05.018