Repolarization abnormalities, arrhythmia and sudden death in canine tachycardia-induced cardiomyopathy.
Repolarization abnormalities, arrhythmia and sudden death in canine tachycardia-induced cardiomyopathy.
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DOI：
10.1016/s0735-1097(97)00193-9
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发表时间：
1997-08
影响因子：
24
通讯作者：
P. Pak;H. B. Nuss;R. Tunin;S. Kääb;G. Tomaselli;E. Marbán;D. Kass
中科院分区：
文献类型：
--
作者：
P. Pak;H. B. Nuss;R. Tunin;S. Kääb;G. Tomaselli;E. Marbán;D. Kass
目标。本研究旨在确定犬心动过速性心力衰竭（HF）模型是否为心脏性猝死（SCD）的有效模型。这样一个建立良好的心衰模型，同时也表现出心律失常和SCD，以及可能引发它们的复极异常，可能有助于心衰中SCD的研究，这仍然缺乏有效的治疗方法。25只狗以250次/分钟的vvi节奏进行3至5周。获得心电图，记录基线和HF后6个部位的左室心内膜单相动作电位（MAPs）。暂停起搏24小时，每周进行动态心电图记录。6只动物（24%）突然死亡，1只有动态心电图记录的多态性室性心动过速（VT）。动态心电图显示，随着心衰的进展，VT的发生率增加。经校正的QT间期（平均[±SD] 311±25至338±25 ms）和90%复极时MAP持续时间（MAPD90）（181±19至209±28 ms）显著延长（p < 0.05）， MAPD90空间弥散度上升40%。我们进一步测试了CsCl对重极化K+电流的抑制是否会优先延长HF中的mapd90。据报道，重极化K+电流在HF中下调。当CsCl浓度为1 mEq/kg体重时，HF犬的mapd90升高86±100 ms，而对照组仅升高28±16 ms （p = 0.002）。从正常心脏和衰竭心脏分离的心肌细胞中观察到类似的CsCl敏感性差异。心动过速引起的心衰表现为恶性心律失常和SCD，并伴有长时间的非均匀复极化，以及在室和细胞水平上对CsCl的敏感性升高。因此，它似乎是研究心衰SCD的机制和治疗的一个有用的模型。
Objectives. This study sought to determine whether the canine model of tachycardia-induced heart failure (HF) is an effective model for sudden cardiac death (SCD) in HF.Background. Such a well established HF model that also exhibits arrhythmias and SCD, along with repolarization abnormalities that could trigger them, may facilitate the study of SCD in HF, which still eludes effective treatment.Methods. Twenty-five dogs were VVI-paced at 250 beats/min for 3 to 5 weeks. Electrocardiograms were obtained, and left ventricular endocardial monophasic action potentials (MAPs) were recorded at six sites at baseline and after HF. Weekly Holter recordings were made with pacing suspended for 24 h.Results. Six animals (24%) died suddenly, one with Holter-documented polymorphic ventricular tachycardia (VT). Holter recordings revealed an increased incidence of VT as HF progressed. Repolarization was significantly (p < 0.05) prolonged, as indexed by a corrected QT interval (mean [±SD] 311 ± 25 to 338 ± 25 ms) and MAP duration measured at 90% repolarization (MAPD90) (181 ± 19 to 209 ± 28 ms), and spatial MAPD90dispersion rose by 40%. We further tested whether CsCl inhibition of repolarizing K+currents, which are reportedly downregulated in HF, might preferentially prolong the MAPD90in HF. With 1 mEq/kg body weight of CsCl, MAPD90rose by 86 ± 100 ms in dogs with HF versus only 28 ± 16 ms in control animals (p = 0.002). Similar disparities in CsCl sensitivity were observed in myocytes isolated from normal and failing hearts.Conclusions. Tachycardia-induced HF exhibits malignant arrhythmia and SCD, along with prolonged, heterogeneous repolarization and heightened sensitivity to CsCl at chamber and cellular levels. Thus, it appears to be a useful model for studying mechanisms and therapy of SCD in HF.