Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania; University of Pittsburgh Medical Center Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania;
Center for Cellular and Systems Electrophysiology, University at Buffalo, State University of New York, Buffalo, New York; Department of Obstetrics and Gynecology, University at Buffalo, State University of New York, Buffalo, New York; and Department of Physiology and Biophysics, University at Buffalo, State University of New York, Buffalo, New York
Am J Physiol Heart Circ Physiol. 2014 Sep 1;307(5):H640-8. doi: 10.1152/ajpheart.00864.2013. Epub 2014 Jun 27.
Sexual dimorphism is a well-established phenomenon, but its degree varies tremendously among species. Since the early days of Einthoven's development of the three-lead galvanometer ECG, we have known there are marked differences in QT intervals of men and women. It required over a century to appreciate the profound implications of sex-based electrophysiological differences in QT interval on the panoply of sex differences with respect to arrhythmia risk, drug sensitivity, and treatment modalities. Little is known about the fundamental mechanism responsible for sex differences in electrical substrate of the human heart, in large part due to the lack of tissue availability. Animal models are an important research tool, but species differences in the sexual dimorphism of the QT interval, the ionic currents underlying the cardiac repolarization, and effects of sex steroids make it difficult to interpolate animal to human sex differences. In addition, in some species, different strains of the same animal model yield conflicting data. Each model has its strengths, such as ease of genetic manipulation in mice or size in dogs. However, many animals do not reproduce the sexual dimorphism of QT seen in humans. To match sex linked prolongation of QT interval and arrhythmogenic phenotype, the current data suggest that the rabbit may be best suited to provide insight into sex differences in humans. In the future, emerging technologies such as induced pluripotent stem cell derived cardiac myocyte systems may offer the opportunity to study sex differences in a controlled hormonal situation in the context of a sex specific human model system.
性别二态性是一个既定的现象，但它在物种间的程度差异极大。自从 Einthoven 开发出三导联电流计心电图以来，我们就已经知道男性和女性的 QT 间期存在明显差异。我们用了一个多世纪的时间才认识到基于性别的 QT 间期电生理差异对心律失常风险、药物敏感性和治疗方式等方面的广泛性别差异的深远影响。对于导致人心电图电生理基质性别差异的基本机制知之甚少，部分原因是组织可用性不足。动物模型是一个重要的研究工具，但 QT 间期的性别二态性、心脏复极化的离子电流以及性激素的作用在动物与人类之间存在差异，这使得动物模型难以推断人类的性别差异。此外，在某些物种中，同一动物模型的不同品系会产生相互矛盾的数据。每个模型都有其优势，例如在小鼠中易于进行基因操作，或在犬类中体型较大。然而，许多动物并不能重现人类 QT 间期的性别二态性。为了匹配与性相关的 QT 间期延长和致心律失常表型，目前的数据表明，兔子可能最适合深入了解人类的性别差异。在未来，新兴技术，如诱导多能干细胞衍生的心肌细胞系统，可能有机会在特定性别的人类模型系统中，在受控激素环境下研究性别差异。
