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Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit
Circulation: Heart Failure ( IF 9.7 ) Pub Date : 2021-06-30 , DOI: 10.1161/circheartfailure.120.007505
Sunil Jit R J Logantha 1, 2 , Xue J Cai 1 , Joseph Yanni 1 , Caroline B Jones 3 , Robert S Stephenson 4, 5 , Luke Stuart 1, 6 , Gillian Quigley 1 , Oliver Monfredi 7, 8 , Shu Nakao 1, 9 , Il-Young Oh 1, 10 , Tobias Starborg 11 , Ashraf Kitmitto 1 , Akbar Vohra 1 , Robert C Hutcheon 12 , Antonio F Corno 13 , Jonathan C Jarvis 4 , Halina Dobrzynski 1, 14 , Mark R Boyett 1 , George Hart 1
Affiliation  

Background:Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs.Methods:Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used.Results:Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca2+-channels, and K+-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P<0.0001), and arrhythmic events in HF. Similar electrical remodeling was seen at the left PF-ventricular junction. In the failing left ventricle, upstroke velocity and amplitude were increased, but action potential duration at 90% repolarization was unaffected.Conclusions:Severe volume- followed by pressure-overload causes rapidly progressing HF with extensive remodeling of PFs. The PF network is central to both arrhythmogenesis and contractile dysfunction and the pathological remodeling may increase the risk of fatal arrhythmias in HF patients.

中文翻译:

兔充血性心力衰竭浦肯野网络的重构

背景:浦肯野纤维 (PFs) 控制心室传导的时间并在心力衰竭 (HF) 患者的心律失常中起关键作用。我们研究了 HF 对 PFs 的影响。方法:超声心动图、心电图、微型计算机断层扫描、定量聚合酶链反应、免疫组织化学、体积电子显微镜和尖锐微电极电生理学。结果:左心室体积诱发兔充血性 HF - 和压力超负荷导致左心室肥大、缩短分数和射血分数减少以及左心室尺寸增加。HF 基线 QRS 波和校正 QT 间期分别延长 17% 和 21%(平均值±SEMs:303±6 ms HF,249±11 ms control;n=8/7;P=0.0002),表明 PF 功能障碍和心室复极受损。微型计算机断层扫描成像显示 HF 中自由运行的左侧 PF 网络体积和长度增加。评估了 40 个离子通道、Ca 2+ 处理蛋白、连接蛋白以及促炎和纤维化标志物的mRNA 水平:左侧和右侧 PF 中分别有 50% 和 35% 失调,而左侧和右侧仅 12.5% 和 7.5% 发生变化心室肌。有趣的通道、Ca 2+ -通道和 K +-通道在左侧 PF 中显着减少。左侧 PF 的微电极记录显示更多的负静息膜电位,动作电位上行速度降低,持续时间延长(90% 复极时的动作电位持续时间:378±24 ms HF,249±5 ms 控制;n=23/38;P<0.0001),以及 HF 中的心律失常事件。在左 PF-心室交界处观察到类似的电重构。在衰竭的左心室,上搏速度和振幅增加,但在 90% 复极时的动作电位持续时间不受影响。结论:严重的容量 - 随后是压力超负荷导致快速进展的 HF 和 PF 的广泛重塑。PF 网络是心律失常和收缩功能障碍的核心,病理重构可能会增加 HF 患者发生致命性心律失常的风险。
更新日期:2021-07-21
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