Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome
Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome
复制标题
DOI：
10.1016/s0735-1097(99)00582-3
复制
发表时间：
2000-03-01
影响因子：
24
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
Shimizu, W;Antzelevitch, C
目的 明确先天性和获得性长 QT 综合征 (LQTS) 中交感神经活动导致危及生命的心律失常发生的细胞机制。 方法 同时记录犬左心室动脉灌注楔形的心外膜 (EPI)、M 和心内膜 (ENDO) 细胞的跨膜动作电位 (AP) 和透壁心电图。我们在 LQT1、LQT2 和 LQT3 形式的 LQTS 模型中检查了 β-肾上腺素能激动剂和拮抗剂对动作电位持续时间 (APD(90))、跨壁复极离散度 (TDR) 和尖端扭转型室性心动过速 (TdP) 发展的影响。 结果 I-Ks 阻滞与 chromanol 293B (LQT1) 均匀延长了三个细胞的 APD(90)类型而不增加 TDR。添加异丙肾上腺素延长了M的QT和APD(90)，但缩短了EPI和ENDO的QT和APD(90)，导致TDR持续增加；尖端扭转型室性心动过速只有在存在异丙肾上腺素的情况下才会发生或诱发。使用 d-索他洛尔 (LQT2) 阻断 I-Kr 并使用 ATX-II (LQT3) 增强晚期 I-Na，比 EPI 和 ENDO 更能延长 M 的 APD(90)，导致 QT 和 TDR 增加。 TdP 在没有异丙肾上腺素的情况下发生。在 LQT2 中，异丙肾上腺素最初延长，然后缩写 M 的 APD(90)，但始终缩写为 EPI，从而暂时增加 TDR 和 TdP 的发生率。在LQT3中，异丙肾上腺素总是缩写为三种细胞类型的APD(90)，导致TDR持续降低和TdP抑制。普萘洛尔可逆转异丙肾上腺素的致心律失常和保护作用。 结论 我们的数据表明，β-肾上腺素能刺激通过增加 LQT1 和 LQT2 中复极的跨壁离散度来诱导 TdP，但通过降低 LQT3 中的离散度来抑制 TdP。数据表明，β 受体阻滞剂对 LQT1 和 LQT2 具有保护作用，但可能促进 LQT3 中的 TdP。 (C) 2000 年由美国心脏病学会发布。
OBJECTIVES To define the cellular mechanisms responsible for the development of life-threatening arrhythmias in response to sympathetic activity in the congenital and acquired long QT syndromes (LQTS).METHODS Transmembrane action potentials (AP) from epicardial (EPI), M and endocardial (ENDO) cells and a transmural electrocardiogram were simultaneously recorded from an arterially perfused wedge of canine left ventricle. We examined the effect of beta-adrenergic agonists and antagonists on action potential duration (APD(90)), transmural dispersion of repolarization (TDR) and the development of Torsade de Pointes (TdP) in models of LQT1, LQT2 and LQT3 forms of LQTS.RESULTS I-Ks block with chromanol 293B (LQT1) homogeneously prolonged APD(90) of the three cell types without increasing TDR. Addition of isoproterenol prolonged QT and APD(90) of M but abbreviated that of EPI and ENDO, causing a persistent increase in TDR; Torsade de Pointes developed or could be induced only in the presence of isoproterenol. I-Kr block with d-sotalol (LQT2) and augmentation of late I-Na with ATX-II (LQT3) prolonged APD(90) of M more than EPI and ENDO, causing increases in QT and TDR. TdP developed in the absence of isoproterenol. In LQT2 isoproterenol initially prolonged, then abbreviated, the APD(90) of M but always abbreviated EPI, thus transiently increasing TDR and the incidence of TdP. In LQT3, isoproterenol always abbreviated APD(90) of the three cell types, causing a persistent decrease in TDR and suppression of TdP. The arrhythmogenic as well as protective actions of isoproterenol were reversed by propranolol.CONCLUSIONS Our data suggest that beta-adrenergic stimulation induces TdP by increasing transmural dispersion of repolarization in LQT1 and LQT2 but suppresses TdP by decreasing dispersion in LQT3. The data indicate that beta-blockers are protective in LQT1 and LQT2 but may facilitate TdP in LQT3. (C) 2000 by the American College of Cardiology.