The effect of lesion size and tissue remodeling on ST deviation in partial-thickness ischemia Mark Potse, PhD,* † Ruben Coronel, MD, PhD, ‡ Stéphanie Falcao, MSc,* § A.-Robert LeBlanc, PhD,* † Alain Vinet, PhD* † From the *Research Center, Sacré-Coeur Hospital, and † Institute of Biomedical Engineering, Université de Montréal, Montréal, Québec, Canada, ‡ Experimental Cardiology Department, Academic Medical Center, University of Amsterdam, The Netherlands, and § Department of Pharmacology, Université de Montréal, Montréal, Québec, Canada. BACKGROUND Myocardial ischemia causes ST segment elevation or depression in electrocardiograms and epicardial leads. ST de- pression in epicardium overlying the ischemic zone indicates that the ischemia is nontransmural. However, nontransmural ischemia does not always cause ST depression. Especially in animal models, ST depression is hard to reproduce. OBJECTIVE The purpose of this study was to determine the cir- cumstances in which ST depression could be expected. METHODS We studied ischemia in a large-scale computer model of the human heart. A realistic representation of the ischemia- induced changes in resting membrane potential was used, which was based on diffusion of extracellular potassium. Ischemia diam- eter, transmural extent, and tissue conductivity were varied. RESULTS Our simulations confirm earlier work showing that par- tial-thickness ischemia, like full-thickness ischemia, typically causes ST elevation in an anisotropic model of the ventricles. However, we identified three situations in which ST depression can occur in overlying leads. The first is a reduced anisotropy ratio of the intracellular conductivity, which may result from hypertrophy and gap-junctional remodeling, circumstances that are likely to accompany ischemia. Second, an increase of the extracellular anisotropy has the same effect. Third, ST depression was found, independent of the anisotropy ratios, in very large and thin isch- emic regions, resembling those that may occur in left-main or multivessel disease. CONCLUSION Both tissue remodeling and geometric factors can explain ST depression in overlying epicardial leads. We note at the same time that ST elevation is found in most circumstances, while depression occurs as a reciprocal effect, even in partial-thickness ischemia. KEYWORDS Ischemia; ST deviation; NSTEMI; Gap junctions; Tissue remodeling; Computer model; Extracellular potassium (Heart Rhythm 2007;4:200 –206) © 2007 Heart Rhythm Society. All rights reserved. Introduction Myocardial ischemia can cause elevation and depression of the ST segment in electrocardiograms (ECGs) and epicar- dial electrograms. Elevation is a sign of myocardial infarc- tion due to complete occlusion of a coronary artery. 1 De- pression, especially in leads proximal to the occluded artery, 2–6 is related to incomplete occlusion and is thought to be mediated by subendocardial ischemia. 7,8 In ischemic tissue the resting membrane potential (V m ) is depolarized with respect to normal tissue. This leads to a depression of the TQ segment in the local extracellular electrogram. 9 –11 With the customary AC-coupled amplifi- ers, the TQ segment must be defined as isoelectric, so the change is observed as an elevation of the ST segment. In addition, true ST elevation can develop in advancing isch- emia because of a reduction of action potential amplitude and duration. 12 For convenience, we describe both TQ and ST changes as ST segment deviations. Elevation of the ST segment is observed in epicardial leads overlying a transmural ischemia. 12 Depression in overlying leads can only occur in partial-thickness isch- emia. 13 In epicardial leads, ST depression has been ob- served when subendocardial ischemia or injury was pro- duced in the in situ dog heart. 11,13 These studies suggested that the ST depression area on the epicardium coincided with the ST elevation area on the endocardium. However, in other studies the deepest ST depression was located over a lateral border of the ischemia, 14,15 and the negative zone on the epicardium did not move during a transition from par- tial-thickness to full-thickness ischemia. 15 Thus, partial- thickness ischemia alone cannot explain ST depression. Recent computer simulations have predicted ST eleva- tion in epicardial leads overlying a partial-thickness isch- emia, 16,17 while ST depression was found adjacent to the Computational resources for this work were provided by the Réseau québécois de calcul de haute performance (RQCHP). M. Potse was sup- ported by a postdoctoral award from the Groupe de recherche en simulation et technologie biomédical (GRSTB), École Polytechnique and Université de Montréal; and by the Research Center of Sacré-Coeur Hospital, Mon- tréal, Québec, Canada. Address reprint requests and correspondence: Dr. M. Potse, Research Center, Sacré-Coeur Hospital, K-3005, 5400 Bou- levard Gouin Ouest, Montréal, Québec H4J 1C5, Canada. E-mail address: mark@potse.nl. (Received July 26, 2006; accepted October 13, 2006.) 1547-5271/$ -see front matter © 2007 Heart Rhythm Society. All rights reserved. doi:10.1016/j.hrthm.2006.10.022