Virtual electrode polarization (VEP) effect is believed to play the key role in electrical stimulation of the heart muscle. However, under certain conditions, including clinical, its existence and importance remain unknown. We investigated the influence of acute tissue damage produced by continuous pacing with strong current (40 mA, 4 ms biphasic pulses with 4Hz frequency for 5 minutes) on the stimulus-generated VEPs and pacing thresholds. Fluorescent optical mapping technique was used to obtain stimulus-induced transmembrane potential distribution around a pacing electrode applied to the ventricular surface of a Langendorffperfused rabbit heart (n=5). The maps and pacing thresholds were recorded before and after the tissue damage. Propidium Iodide (n=2) and Cx43 (n=3) antibody staining was conducted to asses the spatial extents of electroporation and cell uncoupling respectively. Based on these data passive and active 3D bidomain models were built to determine VEP patterns and thresholds for different sizes of the damaged region. The electrophysiological results showed that acute tissue damage led to fainting of the VEP with associated significant increase in pacing thresholds. The damage was expressed in electroporation and cell uncoupling within ~1.0 mm diameter area around the tip of the electrode. According to the computer simulations, cell uncoupling rather than electroporation might be the direct cause of VEP elimination and threshold increase which was nonlinearly dependent on the size of the damaged region. Fiber rotation with depth did not substantially affect the numerical results. The study explains failure to stimulate damaged tissue within the concepts of the VEP theory.