Effect of milrinone to reverse the repolarization defects responsible for the electrocardiographic and arrhythmic manifestations of Brugada syndrome in a coronary-perfused right ventricular wedge model pharmacologically mimicking loss of function of ICa in the setting of a prominent Ito. Recordings obtained at a basic cycle length of 1000 ms. Each grouping represents the transmembrane action potentials (APs) recorded from 2 epicardial (Epi) sites and 1 endocardial (Endo) site together with an ECG, all simultaneously recorded. The Ito agonist NS5806 increases notch and J wave parameters but does not induce arrhythmic activity. The addition of verapamil leads to marked accentuation of the Epi AP notch, giving rise to a large J wave, appearing as an ST segment elevation. Loss of the dome at Epi 2 results in development of phase 2 reentry. Milrinone reverses these repolarization defects, restoring AP duration homogeneity, normalizing the ECG and abolishing all arrhythmic activity. The Brugada phenotype promptly reappears after washout of milrinone. Time calibrations for the recordings are indicated on the right of the figure. The top trace is a stimulus marker.