Ventricular arrhythmias are often triggered by acute myocardial ischemia. The occurrence of lethal arrhythmias is normally related with myocardial injury, alterations of ionic conductance and metabolite concentrations. Ischemia alters the myocardium heterogeneously, differently affecting epicardium, M-cells and endocardium. In this computational study, we calculate the vulnerability to reentry during different stages of regional sub-epicardial ischemia in dissimilar distributions of M cells intro myocardial wall (Antzelevitch’s hypothesis). The main components of ischemia (hypoxia, acidosis and hyperkalemia) were considered in the model. The tissue comprises 150x300 cells, which include different islands or strip of M cells up to 70% tissue area, 20% for epicardial cells and the rest of endocardial zone. The results of the model predict that the vulnerable window for re-entry has a logistic behaviour during sub-epicardial ischemia, with re-entry paths comprising mid-myocardial distributions of tissue.