加齢による心臓変化が不整脈リスクを軽減(Changes in the aging heart may lessen the risk of irregular heartbeats)

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2025-05-20 バージニア工科大学(Virginia Tech)

バージニア工科大学フレイリン生物医学研究所の研究チームは、加齢に伴う心臓細胞の微細構造変化が、不整脈(心拍の乱れ)のリスクを低減する可能性を明らかにした。研究では、心細胞間の微小な隙間「ペリネクサス」が加齢により自然に狭まることが確認され、これが電気的な安定性を高める要因とされた。若年と高齢のモルモット心臓を比較した結果、ペリネクサスが狭い高齢心では不整脈の発生が抑制され、逆に広げるとリスクが増加した。この構造的補償により高齢者の心疾患が「隠れた状態」で存在する可能性も示唆された。

<関連情報>

Age-Associated Perinexal Narrowing Masks Consequences of Sodium Channel Gain of Function in Guinea Pig Hearts

Xiaobo Wu,David Ryan King,Gregory S. Hoeker,Xiaoping Wan,Isabelle Deschenes,Scott R. Johnstone,Robert G. Gourdie,Seth H. Weinberg, and Steven Poelzing
JACC Clinical Electrophysiology  Published onlineMarch 5, 2025
DOI: 10.1016/j.jacep.2024.12.027

Central Illustration

加齢による心臓変化が不整脈リスクを軽減(Changes in the aging heart may lessen the risk of irregular heartbeats)

Abstract

Background

Voltage-gated sodium channel gain of function (NavGOF) is associated with an elevated risk for cardiac arrhythmia. Recent studies have demonstrated that NavGOF can be exacerbated by widening the sodium channel–rich perinexus next to gap junction plaques. Clinically, the incidence of NavGOF-related cardiac events increases with advancing age. However, the impact of aging on perinexal changes and contribution to age-related risk for arrhythmias in NavGOF remains unclear.

Objectives

The aim of this study was to test the hypothesis that age-related increase in arrhythmogenic risk is associated with perinexal remodeling in a model of NavGOF.

Methods

NavGOF was pharmacologically induced in isolated adult (3 months, n = 17) and aged (15 months, n = 19) guinea pig hearts. Epicardial action potentials were optically mapped, and age-associated perinexal remodeling was measured with transmission electron microscopy.

Results

NavGOF electrical phenotypes were comparable between adult and aged hearts despite their exacerbation after perinexal widening. The similarity in these phenotypes may be masked by the narrower perinexus with aging. Furthermore, perinexal widening led to a high incidence of arrhythmias in aged NavGOF hearts, whereas no arrhythmias were induced in adult NavGOF hearts. This increased incidence of arrhythmias in aged NavGOF hearts following perinexal widening may be associated with the increased dispersions of epicardial action potential duration and transmural repolarization.

Conclusions

Perinexal widening exacerbates arrhythmogenic propensity with age, primarily by heterogeneously increasing action potential duration, whereas perinexal narrowing appears to be adaptive and cardio protective in the context of NavGOF.

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