Introduction. The role of a border zone in arrhythmogenesis is not fully understood. In this study we evaluated independent contributions of action potential duration (APD) and dispersion of repolarization (DOR) across the normal/ischemic border to the development of ventricular tachycardia and/or fibrillation (VT/VF). Methods. Ischemia-reperfusion episodes were induced in anesthetized rats by transient coronary occlusion. Unipolar electrograms were recorded from ischemic and perfused areas using a 64-lead array to obtain activation times (ATs), repolarization times (RTs), activation-repolarization intervals (ARIs, a surrogate for APD) and dispersion of repolarization (DOR, as a difference between the earliest and latest RTs). Pinacidil (0.3 mg/kg) and glibenclamide (2 mg/kg) were applied to reduce DOR and to clamp APD at a lower and upper levels, respectively. Results. In the control animals, APD shortened in the ischemic zone, DOR increased to 9±3 ms, and VT/VF developed at reperfusion (6 out of 10). Pre-occlusion application of glibenclamide prolonged APD in the ischemic and perfused zones, decreased DOR to 5±2 ms and did not affect VT/VF development (4 out of 11). Post-occlusion infusion of pinacidil shortened APD in the perfused zone, decreased DOR to 6±3 ms and VT/VF incidence (2 out of 11). Extrasystolic burden at reperfusion was associated with VT/VF incidence in logistic regression analysis (β=1.182, 95%CI 1.008-1.386, p=0.04) and was lesser (p<0.01) in the pinacidil group as compared to the control and glibenclamide groups. Conclusion. The APDs in the perfused zone were a superior arrhythmogenic factor in respect to DOR in the present ischemia-reperfusion model.

In the border zone of ischemic myocardium, extracellular potassium concentration ([K+]) gradually decreases from the ischemic to normal area. Since blood [K+] is equilibrated with the normal tissue [K+], it might affect the [K+] and modify electrophysiological properties in the border zone. The study aimed at evaluation of distribution of depolarization and repolarization characteristics across the ischemic-normal border under blood [K+] variation. 64-lead epicardial mapping was performed in 26 anesthetized rats with [K+] ranged from 2.3 to 6.4 mM in an in vivo model of acute ischemia/reperfusion. The animals with [K+]<4.7 mM (low-normal potassium) had a typical ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K+] >4.7 mM (normal-high potassium) had only the typical ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K+] in linear regression analysis with the adjustment for a zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K+]. The IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K+]. The formation of the border zone was associated with attenuation of IK(ATP) response to hypoxia in low-normal [K+] and increased ESB at reperfusion.

Introduction. Diabetes mellitus (DM) is associated with increased risk of sudden cardiac death, but its role in arrhythmogenesis is not clear. We evaluated contributions of DM duration and hyperglycemia level to development of proarrhythmic electrophysiological changes in the experimental ischemia/reperfusion model. Methods and Results: Ventricular epicardial 64-lead mapping and arrhythmia susceptibility burst-pacing testing were performed in 43 healthy and 55 diabetic (alloxan model) anesthetized rabbits undergoing 15-min left anterior descending coronary artery occlusion, followed by 15-min reperfusion. During ischemia, arrhythmia inducibility did not differ between the groups, but the number of reperfusion ventricular tachycardias and/or fibrillations (VT/VFs) was higher in the DM group (14 out of 55) as compared to control (3 out of 43, p=0.017). In the diabetic animals, both DM duration and glucose concentration were associated with reperfusion VT/VF development in univariate logistic regression analysis (OR 1.058; 95% CI 1.025-1.092; p < 0.001; and OR 1,119; 95% CI 1,045-1,198; p = 0.001; respectively). However, only the DM duration remained an independent predictor of reperfusion VT/VF in multivariate logistic regression analysis (OR 1.060; 95% CI 1.006 1.117; p = 0.029). Among mapping parameters, DM duration was associated with the prolongation of total ventricular activation duration (B 0.152; 95% CI 0.049-0.255; p=0.005) and activation-repolarization intervals (ARIs) (B 0.900; 95% CI 0.315-1.484; p=0.003). The prolonged ARI was the only mapping characteristic predicting reperfusion VT/VF development (OR 1.028; 95% CI 1.009-1.048; p = 0.004). Conclusions: The DM duration-dependent prolongation of ventricular repolarization presents a link between DM development and reperfusion VT/VF inducibility.