Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34096 Montpellier, France; email:
LabEx Ion Channels Science and Therapeutics (ICST), 06560 Nice, France.
Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:757-778. doi: 10.1146/annurev-pharmtox-031120-115815. Epub 2020 Oct 5.
The spontaneous activity of the sinoatrial node initiates the heartbeat. Sino-atrial node dysfunction (SND) and sick sinoatrial (sick sinus) syndrome are caused by the heart's inability to generate a normal sinoatrial node action potential. In clinical practice, SND is generally considered an age-related pathology, secondary to degenerative fibrosis of the heart pacemaker tissue. However, other forms of SND exist, including idiopathic primary SND, which is genetic, and forms that are secondary to cardiovascular or systemic disease. The incidence of SND in the general population is expected to increase over the next half century, boosting the need to implant electronic pacemakers. During the last two decades, our knowledge of sino-atrial node physiology and of the pathophysiological mechanisms underlying SND has advanced considerably. This review summarizes the current knowledge about SND mechanisms and discusses the possibility of introducing new pharmacologic therapies for treating SND.
窦房结的自发性活动启动心跳。窦房结功能障碍(SND)和病态窦房结(病态窦房结)综合征是由于心脏无法产生正常的窦房结动作电位引起的。在临床实践中,SND 通常被认为是一种与年龄相关的病理学,继发于心脏起搏器组织的退行性纤维化。然而,其他形式的 SND 也存在,包括原发性 SND,这是遗传性的,以及继发于心血管或系统性疾病的形式。预计在未来半个世纪,SND 在普通人群中的发病率将会增加,这将增加对植入电子起搏器的需求。在过去的二十年中,我们对窦房结生理学和 SND 病理生理机制的认识有了很大的提高。这篇综述总结了目前关于 SND 机制的知识,并讨论了引入新的药物治疗 SND 的可能性。