Libin Cardiovascular Institute, Department of Cardiac Sciences, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Heart Rhythm. 2021 Jan;18(1):118-129. doi: 10.1016/j.hrthm.2020.08.019. Epub 2020 Sep 7.
Atrial fibrillation (AF) is highly prevalent in diabetes mellitus (DM), yet the basis for this finding is poorly understood. Type 2 DM may be associated with unique patterns of atrial electrical and structural remodeling; however, this has not been investigated in detail.
The purpose of this study was to investigate AF susceptibility and atrial electrical and structural remodeling in type 2 diabetic db/db mice.
AF susceptibility and atrial function were assessed in male and female db/db mice and age-matched wildtype littermates. Electrophysiological studies were conducted in vivo using intracardiac electrophysiology and programmed stimulation. Atrial electrophysiology was also investigated in isolated atrial preparations using high-resolution optical mapping and in isolated atrial myocytes using patch-clamping. Molecular biology studies were performed using quantitative polymerase chain reaction and western blotting. Atrial fibrosis was assessed using histology.
db/db mice were highly susceptible to AF in association with reduced atrial conduction velocity, action potential duration prolongation, and increased heterogeneity in repolarization in left and right atria. In db/db mice, atrial K currents, including the transient outward current (I) and the ultrarapid delayed rectifier current (I), were reduced. The reduction in I occurred in association with reductions in Kcnd2 mRNA expression and K4.2 protein levels. The reduction in I was not related to gene or protein expression changes. Interstitial atrial fibrosis was increased in db/db mice.
Our study demonstrates that increased susceptibility to AF in db/db mice occurs in association with impaired electrical conduction as well as electrical and structural remodeling of the atria.
心房颤动（AF）在糖尿病（DM）中发病率较高，但对这一发现的基础知之甚少。2 型糖尿病可能与独特的心房电和结构重塑模式有关；然而，这尚未得到详细研究。
本研究旨在研究 2 型糖尿病 db/db 小鼠的 AF 易感性以及心房电和结构重塑。
评估雄性和雌性 db/db 小鼠以及年龄匹配的野生型同窝小鼠的 AF 易感性和心房功能。使用心内电生理学和程控刺激进行体内电生理研究。使用高分辨率光学映射在分离的心房制剂中以及使用膜片钳在分离的心房细胞中研究心房电生理。使用定量聚合酶链反应和 Western 印迹进行分子生物学研究。使用组织学评估心房纤维化。
db/db 小鼠极易发生 AF，与左、右心房的心房传导速度降低、动作电位持续时间延长以及复极异质性增加有关。在 db/db 小鼠中，心房 K 电流，包括瞬时外向电流（I）和超快延迟整流电流（I），减少。I 的减少与 Kcnd2 mRNA 表达和 K4.2 蛋白水平的降低有关。I 的减少与基因或蛋白表达变化无关。db/db 小鼠的间质心房纤维化增加。
我们的研究表明，db/db 小鼠 AF 易感性增加与电传导受损以及心房的电和结构重塑有关。
