The changes in EM window in hypokalemic hearts were examined in Ethylvanillin parallel with more conventional electrophysiological assessments, including measurements of ventricular conduction times, refractoriness, excitation wavelength index, and spatial repolarization gradients. This study suggests that hypokalemia-induced arrhythmogenicity may not be accounted for by the reversed relationships between the duration of electrical and mechanical systole, which have been reported to occur in other experimental models of electrical instability. Indeed, although hypokalemia was found to prolong repolarization and increase the occurrence of tachyarrhythmia in perfused guinea-pig and rabbit hearts, the duration of mechanical systole remained invariably longer compared to the QT interval, thereby contributing to the positive EM window, as assessed during both steady-state pacing and extrasystolic stimulations. Nevertheless, proarrhythmic effects of hypokalemia were associated with slowed LV-to-RV conduction and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Furthermore, hypokalemia evoked non-uniform prolongation of repolarization time at distinct epicardial recording sites, which resulted in amplified spatial repolarization gradients. These findings therefore suggest that in hypokalemic hearts, the abFenofibric acid normal changes in ventricular conduction times, refractoriness, excitation wavelength, and repolarization gradients are more important mechanistic determinants of arrhythmic substrate, as compared to the changes in EM window. Likewise, a positive difference between the duration of mechanical systole and QT interval seen in normal human subjects, may be reversed upon acute adrenergic stimulation produced by b-adrenoreceptor agonist infusion or intensive physical exercise. Importantly, in patients with healed myocardial infarction, the long-term survival rate was found to be 2.6-fold lower in a patient subgroup with a negative EM window, thereby indicating that this parameter may be used to predict the mortality risk in coronary artery disease.