Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Second Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taoyuan, Taiwan.
Heart Rhythm. 2013 Oct;10(10):1516-24. doi: 10.1016/j.hrthm.2013.07.003. Epub 2013 Jul 5.
A secondary rise of intracellular Ca(2+) (Cai) and an upregulation of apamin-sensitive K(+) current (I(KAS)) are characteristic findings of failing ventricular myocytes. We hypothesize that apamin, a specific I(KAS) blocker, may induce torsades de pointes (TdP) ventricular arrhythmia from failing ventricles exhibiting secondary rises of Cai.
To test the hypothesis that small conductance Ca(2+) activated IKAS maintains repolarization reserve and prevents ventricular arrhythmia in a rabbit model of heart failure (HF).
We performed Langendorff perfusion and optical mapping studies in 7 hearts with pacing-induced HF and in 5 normal control rabbit hearts. Atrioventricular block was created by cryoablation to allow pacing at slow rates.
The left ventricular ejection fraction reduced from 69.1% [95% confidence interval 62.3%-76.0%] before pacing to 30.4% [26.8%-34.0%] (N = 7; P < .001) after pacing. The corrected QT interval in failing ventricles was 337 [313-360] ms at baseline and 410 [381-439] ms after applying 100 nmol/L of apamin (P = .01). Apamin induced early afterdepolarizations (EADs) in 6 ventricles, premature ventricular beats (PVBs) in 7 ventricles, and polymorphic ventricular tachycardia consistent with TdP in 4 ventricles. The earliest activation site of EADs and PVBs always occurred at the site with long action potential duration and large amplitude of the secondary rises of Ca(i). Apamin induced secondary rises of Ca(i) in 1 nonfailing ventricle, but no EAD or TdP were observed.
In HF ventricles, apamin induces EADs, PVBs, and TdP from areas with secondary rises of Ca(i). I(KAS) is important in maintaining repolarization reserve and preventing TdP in HF ventricles.
细胞内钙离子（Cai）的二次升高和阿米巴毒素敏感钾电流（I（KAS））的上调是衰竭心室肌细胞的特征性发现。我们假设阿米巴毒素，一种特定的 I（KAS）阻断剂，可能会从表现出二次 Cai 升高的衰竭心室中引发尖端扭转型室性心动过速（TdP）室性心律失常。
测试以下假说，即小电导钙激活的 IKAS 维持复极化储备并防止心力衰竭（HF）兔模型中的室性心律失常。
我们在 7 只起搏诱导 HF 兔心和 5 只正常对照兔心进行 Langendorff 灌注和光学标测研究。通过冷冻消融创建房室传导阻滞，以允许在较慢的速率下起搏。
左心室射血分数从起搏前的 69.1%[95%置信区间 62.3%-76.0%]降低到起搏后的 30.4%[26.8%-34.0%]（N=7；P<.001）。在衰竭的心室中，校正的 QT 间隔在基础状态下为 337[313-360]ms，在用 100nmol/L 的阿米巴毒素处理后为 410[381-439]ms（P=0.01）。阿米巴毒素在 6 个心室中诱导早期后除极（EAD），在 7 个心室中诱导过早的室性搏动（PVB），在 4 个心室中诱导符合 TdP 的多形性室性心动过速。EAD 和 PVB 的最早激活部位始终发生在动作电位持续时间长且 Cai 二次升高幅度大的部位。阿米巴毒素在 1 个非衰竭心室中诱导了 Cai 的二次升高，但未观察到 EAD 或 TdP。
在 HF 心室中，阿米巴毒素从 Cai 二次升高的区域诱导 EAD、PVB 和 TdP。I（KAS）在维持 HF 心室的复极化储备和防止 TdP 方面非常重要。
