The aim of this study is to examine how structural discontinuity and functional remodeling changes the susceptibility to alternans of action potential duration (APD) in a rabbit model of chronic myocardial infarction (MI). Optical mapping experiments using voltage-sensitive dyes were performed in 14 rabbit hearts. We found that (1) APD alternans starts at a significantly slower pacing rate in hearts with MI (n = 7) than in normal hearts (n = 7), with the original sites of alternans of APD located in the infarct region and infarct adjacent regions. (2) Alternans of activation cycle length (CL) precedes the occurrence of spatially discordant alternans of APD, with the regions of activation CL alternans located in the infarct adjacent regions. Based on these results, we conclude that susceptibility to alternans are significantly enhanced in this rabbit model of chronic MI, and the enhancement is strongly correlated to structural and functional heterogeneity imposed by the infarction.