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Age is a major driver of the risk of acute myocardial infarction and malignant ventricular arrhythmias. However, age-related changes in the ischemic myocardium remain largely unclear. The present study aimed to evaluate electrophysiological responses of myocardium to experimental ischemia-reperfusion conditions in rats aged 3, 12, and 24 months. Epicardial mapping (64 leads) was performed in a total of 34 anesthetized animals. In each lead, activation time (AT), end of repolarization time (RT), and activation-repolarization interval (ARI), were measured as dV/dt min during QRS, dV/dt max during T-wave, and RT – AT difference, respectively. Dispersion of repolarization (DOR) was determined as the RTmax – RTmin difference throughout all leads. Ischemia was induced by a 5-min ligation of the left anterior descending coronary artery. It was found that the 24-month-old rats had shorter baseline ATs and ARIs (p < 0.05), greater AT prolongation and less ARI shortening at ischemia (p < 0.05) and more complete recovery of the ARI at reperfusion (p < 0.001; all comparisons vs 3-month-old animals). At reperfusion, the absolute values of AT and DOR were lower in the old and middle-aged animals as compared to the young rats (p < 0.05); however, the absolute values of ARI durations did not differ between the groups. The data obtained suggest existence of age-related differences in the sensitivity of myocardium to ischemia-reperfusion conditions and that old animals are more susceptible to adverse changes regarding activation spread and more resilient regarding repolarization characteristics as compared to young adult animals. [ABSTRACT FROM AUTHOR]

Melatonin treatment was reported to reduce the risk of cardiac arrhythmias, and crucial for this antiarrhythmic action was the effect of melatonin on activation spread. The aim of the present study was evaluation of the mechanisms of this activation enhancement. Experiments were performed in a total of 123 control and melatonin‐treated (10 mg/kg, daily, for 7 days) male Wistar rats. In epicardial mapping studies (64 leads, interlead distance 0.5 mm) in the anesthetized animals, activation times (ATs) were determined in each lead as dV/dt minimum during QRS complex under sinus rhythm. Epicardial pacing was performed to measure conduction velocity (CV) across the mapped area. Average left ventricular ATs were shorter in the treated animals as compared to the controls, whereas the minimal epicardial ATs indicating the duration of activation propagation via the ventricular conduction system did not differ between the groups. CV was higher in the treated groups indicating that melatonin affected conduction via contractile myocardium The area of Cx43‐derived fluorescence, as well as the expression of Cx43 protein, was similar in ventricles in the control and melatonin‐treated groups. Expression of Gja1 gene transcripts encoding Cx43, was increased in the last group. An uncoupling agent octanol modified myocardial conduction properties (time of activation, action potential upstroke velocity, passive electrotonic phase duration) similarly in both groups. On the other hand, the expression of both Scn5a gene transcripts encoding Nav1.5 proteins, as well as peak density of transmembrane sodium current were increased in the ventricular myocytes from the melatonin‐treated animals. Thus, a week‐long melatonin treatment caused the increase of conduction velocity via enhancement of sodium channel proteins expression and increase of sodium current in the ventricular myocytes. [ABSTRACT FROM AUTHOR]

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). 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), activationrepolarization 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. 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. In conclusion, the results of this study suggest that the APDs in the perfused zone were a superior arrhythmogenic factor in respect to DOR in the present ischemia-reperfusion model. [ABSTRACT FROM AUTHOR]