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Mechanistic links have been suggested between repolarization alternans (RPA) and the onset of ventricular tachycardia (VT) and/or fibrillation. Endocardial detection of RPA may, therefore, be an important step in future device-based treatments of arrhythmias. Here, we investigate if RPA could be detected during acute ischemia using an implantable cardioverter defibrillator (ICD) lead (tip to distal coil) located in the right ventricular apex. In 18 pigs, the right coronary (n=10) or left anterior descending coronary (n=8) artery was occluded for 10 min using a balloon catheter, followed by reperfusion for 30 min, and re-occlusion for 30 min. RPA magnitude, computed using the modified moving average (MMA) method, showed a sharp increase in all 18 animals, from a mean baseline level of 1.9±1.3 mV to 3.0±1.3 mV during first occlusion (p<0.001). RPA magnitude showed a prominent increase in 10 animals during re-occlusion, from a mean baseline level of 1.7±1.0 mV to 3.3±1.5 mV (p<0.001). The protocol was terminated during the first two stages of occlusion and reperfusion for the remaining 8 animals due to the occurrence of ventricular fibrillation (VF). These results confirm that RPA increases under ischemic conditions and that it is possible to detect and track RPA dynamics with an ICD lead that is positioned in a clinically realistic location. Such an approach may be useful in formulating improved arrhythmia detection and control algorithms.