(A) A normal surface V₂ recording together with endocardial (Endo), midmyocardial (M), and epicardial (Epi) action potential (AP) recordings. (B) The development of a transmural voltage gradient between epicardium and endocardium, giving rise to a saddleback configuration in V₂ (type II Brugada pattern). (C) Further transmural voltage changes producing a coved pattern in V₂ (type I pattern). (D) Loss of the dome in the epicardial recording and enhanced coved pattern in V₂. (E) Potential differences between polarized and adjacent depolarized cells may lead to re-entry (phase 2). ECG = electrocardiogram. Reprinted with permission from Antzelevitch (4).

Each panel shows action potentials recorded from 2 epicardial sites and 1 endocardial site, together with a transmural electrocardiogram. Control recordings were obtained at a basic cycle length (BCL) of 2,000 ms, whereas terfenadine data were recorded at a BCL of 800 ms after a brief period of pacing at a BCL of 400 ms. (A) Terfenadine (5 µM)-induced, heterogeneous loss of action potential dome, ST-segment elevation, and phase 2 re-entry (arrow) in a male right ventricular (RV) wedge preparation. (B) Terfenadine fails to induce Brugada phenotype in a female RV wedge preparation. (C) Polymorphic VT triggered by spontaneous phase 2 re-entry in a male preparation. (D) Incidence of phase 2 re-entry in male (6 of 7) versus female (2 of 7) RV wedge preparations when perfused with 5 µM terfenadine for up to 2 h. Abbreviations as in Figure 1. Modified with permission from Antzelevitch (4).