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缺血再灌注破坏未成熟房室起搏器的节律性:新生兔术后心律失常的一个诱发因素。

Ischemia-reperfusion destabilizes rhythmicity in immature atrioventricular pacemakers: A predisposing factor for postoperative arrhythmias in neonate rabbits.

作者信息

Chenliu Cici, Sheng Xiaoye, Dan Pauline, Qu Yang, Claydon Victoria E, Lin Eric, Hove-Madsen Leif, Sanatani Shubhayan, Tibbits Glen F

机构信息

Cardiovascular Sciences, Child and Family Research Institute, Vancouver, BC, Canada; Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada.

Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada.

出版信息

Heart Rhythm. 2016 Dec;13(12):2348-2355. doi: 10.1016/j.hrthm.2016.07.022. Epub 2016 Jul 20.

Abstract

BACKGROUND

Postoperative arrhythmias such as junctional ectopic tachycardia and atrioventricular block are serious postoperative complications for children with congenital heart disease. We hypothesize that ischemia-reperfusion (I/R) related changes exacerbate these postoperative arrhythmias in the neonate heart and administration of postoperative inotropes is contributory.

OBJECTIVE

The purpose of this study was to study the effects of I/R and postischemic dopamine application on automaticity and rhythmicity in immature and mature pacemaker cells and whole heart preparations.

METHODS

Single pacemaker cells and whole heart models of postoperative arrhythmias were generated in a rabbit model encompassing 3 primary risk factors: age, I/R exposure, and dopamine application. Single cells were studied using current clamp and line scan confocal microscopy, whereas whole hearts were studied using optical mapping.

RESULTS

Four responses were observed in neonatal atrioventricular nodal cells (AVNCs): slowing of AVNC automaticity (from 62±10 to 36 ± 12 action potentials per minute, P<.05); induction of arrhythmicity or increased beat-to-beat variability (0.08 ± 0.04 to 3.83 ± 1.79, P<.05); altered automaticity (subthreshold electrical fluctuations); and disruption of calcium transients. In contrast, these responses were not observed in mature AVNCs or neonatal sinoatrial cells. In whole heart experiments, neonatal hearts experienced persistent postischemia arrhythmias of varying severity, whereas mature hearts exhibited no arrhythmias or relatively transient ones.

CONCLUSION

Neonatal pacemaker cells and whole hearts demonstrate a susceptibility to I/R insults resulting in alterations in automaticity, which may predispose neonates to postoperative arrhythmias such as junctional ectopic tachycardia and atrioventricular block.

摘要

背景

诸如交界性异位性心动过速和房室传导阻滞等术后心律失常是先天性心脏病患儿严重的术后并发症。我们推测,缺血再灌注(I/R)相关变化会加剧新生儿心脏的这些术后心律失常,且术后使用正性肌力药物也有促成作用。

目的

本研究旨在探讨I/R及缺血后应用多巴胺对未成熟和成熟起搏细胞及全心标本的自律性和节律性的影响。

方法

在一个包含3个主要危险因素(年龄、I/R暴露和多巴胺应用)的兔模型中建立术后心律失常的单个起搏细胞和全心模型。使用电流钳和线扫描共聚焦显微镜研究单个细胞,而使用光学标测研究全心。

结果

在新生兔房室结细胞(AVNCs)中观察到4种反应:AVNCs自律性减慢(从每分钟62±10次动作电位降至36±12次,P<0.05);诱导心律失常或逐搏变异性增加(从0.08±0.04增至3.83±1.79,P<0.05);自律性改变(阈下电波动);以及钙瞬变破坏。相比之下,在成熟的AVNCs或新生兔窦房结细胞中未观察到这些反应。在全心实验中,新生兔心脏在缺血后出现持续的、严重程度不同的心律失常,而成熟心脏未出现心律失常或仅有相对短暂的心律失常。

结论

新生兔起搏细胞和全心对I/R损伤敏感,导致自律性改变,这可能使新生儿易发生术后心律失常,如交界性异位性心动过速和房室传导阻滞。

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