Department of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, Russia.
Department of Biomedical Technology, Faculty of Biomedical Engineering, Czech Technical University in Prague, Kladno, Czech Republic.
J Physiol Pharmacol. 2021 Oct;72(5). doi: 10.26402/jpp.2021.5.04. Epub 2022 Feb 12.
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), 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. 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.
正常/缺血交界区在心律失常发生中的作用尚不完全清楚。本研究旨在评估动作电位时程（APD）和复极离散度（DOR）在正常/缺血交界区对室性心动过速和/或颤动（VT/VF）发展的独立贡献。通过短暂的冠状动脉闭塞在麻醉大鼠中诱导缺血再灌注发作。使用 64 导联数组从缺血区和灌注区记录单极电图，以获得激活时间（AT）、复极时间（RT）、激活-复极间期（ARIs，APD 的替代指标）和复极离散度（DOR，作为最早和最晚 RT 之间的差异）。应用匹那地尔（0.3mg/kg）和格列本脲（2mg/kg）降低 DOR 并分别将 APD 钳制在上限和下限水平。在对照动物中，缺血区的 APD 缩短，DOR 增加至 9±3ms，再灌注时发生 VT/VF（10 例中 6 例）。在缺血前应用格列本脲延长了缺血区和灌注区的 APD，将 DOR 降低至 5±2ms，并且不影响 VT/VF 的发生（11 例中 4 例）。缺血后输注匹那地尔缩短了灌注区的 APD，将 DOR 降低至 6±3ms，并且 VT/VF 的发生率（11 例中 2 例）降低。再灌注时的期前收缩负担与 VT/VF 的发生率在逻辑回归分析中相关（β=1.182，95%CI 1.008-1.386，p=0.04），并且在匹那地尔组与对照组和格列本脲组相比更小（p<0.01）。总之，本研究结果表明，在本缺血再灌注模型中，与 DOR 相比，灌注区的 APD 是一种更好的致心律失常因素。
