Electrical Stimulation of Artificial Heart Muscle: A Look Into the Electrophysiologic and Genetic Implications.
Electrical Stimulation of Artificial Heart Muscle: A Look Into the Electrophysiologic and Genetic Implications.
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人工心肌的电刺激：电生理和遗传影响的研究。
DOI：
10.1097/mat.0000000000000486
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Birla,RaviK
中科院分区：
文献类型：
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作者：
Mohamed,MohamedA;Islas,JoseF;Schwartz,RobertJ;Birla,RaviK
用于治疗心肌梗死或生物起搏器的组织工程心脏的发展一直受到大多数药物或非协同构建物的生产的阻碍。这些结构的电刺激（ES）已被证明产生具有更大的抽搐力和更好的肾上腺素能反应的组织。为了进一步了解ES效应的机制，我们制造了一种生物反应器，能够同时向多个构建体提供各种类型的连续或间歇波形。在这项研究中，我们研究了间歇性双相方波对我们的人工心肌（AHM）组成的新生大鼠心肌细胞和纤维蛋白凝胶的影响。抽搐力量，自发收缩率，生物电位，基因表达谱，和组织学观察进行了检查的ES协议超过12天的培养期。我们证明了样品之间的一致性改善的抽搐力和收缩率，和更高的归一化抽搐力振幅电刺激AHM。AHM内的电生理学改善通过电刺激AHM的更高的传导速度和更低的电响应潜伏期来观察。表达关键电生理和结构标记的基因在培养的第6天和第8天达到峰值，仅在ES启动后几天。这些结果可用于优化策略，以建立用于产生能够以收缩或电生理能力替换受损心脏组织的AHM的方案。优化的AHM可以导致心力衰竭的替代治疗，并缓解有限的供体供应危机。
Development of tissue-engineered hearts for treatment of myocardial infarction or biologic pacemakers has been hindered by the production of mostly arrhythmic or in-synergistic constructs. Electrical stimulation (ES) of these constructs has been shown to produce tissues with greater twitch force and better adrenergic response. To further our understanding of the mechanisms underlying the effect of ES, we fabricated a bioreactor capable of delivering continuous or intermittent waveforms of various types to multiple constructs simultaneously. In this study, we examined the effect of an intermittent biphasic square wave on our artificial heart muscle (AHM) composed of neonatal rat cardiac cells and fibrin gel. Twitch forces, spontaneous contraction rates, biopotentials, gene expression profiles, and histologic observations were examined for the ES protocol over a 12 day culture period. We demonstrate improved consistency between samples for twitch force and contraction rate, and higher normalized twitch force amplitudes for electrically stimulated AHMs. Improvements in electrophysiology within the AHM were noted by higher conduction velocities and lower latency in electrical response for electrically stimulated AHMs. Genes expressing key electrophysiologic and structural markers peaked at days 6 and 8 of culture, only a few days after the initiation of ES. These results may be used for optimization strategies to establish protocols for producing AHMs capable of replacing damaged heart tissue in either a contractile or electrophysiologic capacity. Optimized AHMs can lead to alternative treatments to heart failure and alleviate the limited donor supply crisis.