Adamson Philip B, Barr Roger C, Callans David J, Chen Peng-Sheng, Lathrop David A, Makielski Jonathan C, Nerbonne Jeanne M, Nuss H Bradley, Olgin Jeffrey E, Przywara Dennis A, Rosen Michael R, Rozanski George J, Spach Madison S, Yamada Kathryn A
University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Heart Rhythm. 2005 Jun;2(6):650-9. doi: 10.1016/j.hrthm.2005.03.009.
Cardiac arrhythmias continue to pose a major medical challenge and significant public health burden. Atrial fibrillation, the most prevalent arrhythmia, affects more than two million Americans annually and is associated with a twofold increase in mortality. In addition, more than 250,000 Americans each year suffer ventricular arrhythmias, often resulting in sudden cardiac death. Despite the high incidence and societal impact of cardiac arrhythmias, presently there are insufficient insights into the molecular mechanisms involved in arrhythmia generation, propagation, and/or maintenance or into the molecular determinants of disease risk, prognosis, and progression. In addition, present therapeutic strategies for arrhythmia abatement often are ineffective or require palliative device therapy after persistent changes in the electrical and conduction characteristics of the heart have occurred, changes that appear to increase the risk for arrhythmia progression. This article reviews our present understanding of the complexity of mechanisms that regulate cardiac membrane excitability and cardiac function and explores the role of derangements in these mechanisms that interact to induce arrhythmogenic substrates. Approaches are recommended for future investigations focused on providing new mechanistic insights and therapeutic interventions.
心律失常仍然是一个重大的医学挑战，并带来了巨大的公共卫生负担。心房颤动是最常见的心律失常，每年影响超过200万美国人，并且与死亡率增加两倍相关。此外，每年有超过25万美国人发生室性心律失常，常常导致心源性猝死。尽管心律失常的发病率很高且对社会有影响，但目前对于心律失常的发生、传播和/或维持所涉及的分子机制，以及疾病风险、预后和进展的分子决定因素，仍缺乏足够的认识。此外，目前用于减轻心律失常的治疗策略往往无效，或者在心脏的电和传导特性发生持续性改变后需要姑息性器械治疗，而这些改变似乎会增加心律失常进展的风险。本文综述了我们目前对调节心脏膜兴奋性和心脏功能机制复杂性的理解，并探讨了这些机制紊乱在相互作用中诱导致心律失常基质的作用。建议采取一些方法用于未来的研究，重点是提供新的机制见解和治疗干预措施。
