Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Heart Rhythm. 2018 May;15(5):761-769. doi: 10.1016/j.hrthm.2018.01.016. Epub 2018 Jan 8.
Apamin-sensitive small conductance calcium-activated K current (I) is up-regulated during ventricular pacing and masks short-term cardiac memory (CM).
The purpose of this study was to determine the role of I in long-term CM.
CM was created with 3-5 weeks of ventricular pacing and defined by a flat or inverted T wave off pacing. Epicardial optical mapping was performed in both paced and normal ventricles. Action potential duration (APD) was determined during right atrial pacing. Ventricular stability was tested before and after I blockade. Four paced hearts and 4 normal hearts were used for western blotting and histology.
There were no significant differences in either echocardiographic parameters or fibrosis levels between groups. Apamin induced more APD prolongation in CM than in normal ventricles (mean [95% confidence interval]: 9.6% [8.8%-10.5%] vs 3.1% [1.9%-4.3%]; P <.001). Apamin significantly lengthened APD in the CM model at late activation sites, indicating significant I up-regulation at those sites. The CM model also had altered Ca handling, with the 50% Ca transient duration and amplitude increased at distal sites compared to a proximal site (near the pacing site). After apamin, the CM model had increased ventricular fibrillation (VF) inducibility (paced vs control: 33/40 (82.5%) vs 7/20 (35%); P <.001) and longer VF durations (124 vs 26 seconds; P <.001).
Chronic ventricular pacing increases Ca transients at late activation sites, which activates I to maintain repolarization reserve. I blockade increases VF vulnerability in chronically paced rabbit ventricles.
在心室起搏期间，阿帕敏敏感的小电导钙激活钾电流（I）上调，并掩盖了短期心脏记忆（CM）。
本研究旨在确定 I 在长期 CM 中的作用。
通过 3-5 周的心室起搏创建 CM，并通过起搏后出现平坦或倒置的 T 波来定义。在起搏和正常心室中进行心外膜光学标测。在右心房起搏期间确定动作电位持续时间（APD）。在 I 阻断前后测试心室稳定性。使用 4 个起搏心脏和 4 个正常心脏进行 Western 印迹和组织学分析。
各组之间的超声心动图参数或纤维化水平均无显著差异。阿帕敏在 CM 中引起的 APD 延长大于正常心室（平均[95%置信区间]：9.6%[8.8%-10.5%] vs 3.1%[1.9%-4.3%]；P<0.001）。阿帕敏在 CM 模型的晚期激活部位明显延长 APD，表明这些部位的 I 上调明显。CM 模型还改变了 Ca 处理，与近端部位（靠近起搏部位）相比，远部位的 50%Ca 瞬变持续时间和幅度增加。在用阿帕敏后，CM 模型的心室颤动（VF）易感性增加（起搏与对照：33/40（82.5%）与 7/20（35%）；P<0.001），VF 持续时间延长（124 与 26 秒；P<0.001）。
慢性心室起搏增加晚期激活部位的 Ca 瞬变，激活 I 以维持复极储备。I 阻断增加慢性起搏兔心室的 VF 易损性。
