Species-Dependent Mechanisms of Cardiac Arrhythmia: A Cellular Focus.
Species-Dependent Mechanisms of Cardiac Arrhythmia: A Cellular Focus.
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DOI：
10.1177/1179546816686061
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Louch WE
中科院分区：
文献类型：
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作者：
Edwards AG;Louch WE
虽然室性心律失常仍然是发病率和死亡率的主要原因，但可用的抗心律失常药物的疗效有限。新型临床相关抗肿瘤药物的开发进展令人失望，部分原因可能是临床前试验中使用的人类和动物模型之间存在差异。然而，这种差异目前难以预测，需要更好地了解跨物种的心律失常机制。为此，我们目前审查种间的相似性和差异，在基本的心肌细胞电生理学和目前的理解的机制，产生后去极化和折返。我们特别强调了小型啮齿动物的专利缺陷，以重现细胞和组织水平的心律失常基质，这些基质被认为是人类心室的关键。尽管从较大的动物模型翻译更容易，但仍然存在差异，并且由于组织可用性低，对人类心室生理学的不完整知识可能使解释复杂化。因此，我们指出数学建模作为理解和治疗人类心律失常的翻译桥梁的好处。
Although ventricular arrhythmia remains a leading cause of morbidity and mortality, available antiarrhythmic drugs have limited efficacy. Disappointing progress in the development of novel, clinically relevant antiarrhythmic agents may partly be attributed to discrepancies between humans and animal models used in preclinical testing. However, such differences are at present difficult to predict, requiring improved understanding of arrhythmia mechanisms across species. To this end, we presently review interspecies similarities and differences in fundamental cardiomyocyte electrophysiology and current understanding of the mechanisms underlying the generation of afterdepolarizations and reentry. We specifically highlight patent shortcomings in small rodents to reproduce cellular and tissue-level arrhythmia substrate believed to be critical in human ventricle. Despite greater ease of translation from larger animal models, discrepancies remain and interpretation can be complicated by incomplete knowledge of human ventricular physiology due to low availability of explanted tissue. We therefore point to the benefits of mathematical modeling as a translational bridge to understanding and treating human arrhythmia.