Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Cellular & Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Int J Mol Sci. 2024 Nov 20;25(22):12464. doi: 10.3390/ijms252212464.
Type 2 diabetes mellitus (T2DM) is one of the most significant health issues worldwide, with associated healthcare costs estimated to surpass USD 1054 billion by 2045. The leading cause of death in T2DM patients is the development of cardiovascular disease (CVD). In the early stages of T2DM, patients develop cardiovascular autonomic dysfunction due to the withdrawal of cardiac parasympathetic activity. Diminished cardiac parasympathetic tone can lead to cardiac arrhythmia-related sudden cardiac death, which accounts for 50% of CVD-related deaths in T2DM patients. Regulation of cardiovascular parasympathetic activity is integrated by neural circuitry at multiple levels including afferent, central, and efferent components. Efferent control of cardiac parasympathetic autonomic tone is mediated through the activity of preganglionic parasympathetic neurons located in the cardiac extensions of the vagus nerve that signals to postganglionic parasympathetic neurons located in the intracardiac ganglia (ICG) on the heart. Postganglionic parasympathetic neurons exert local control on the heart, independent of higher brain centers, through the release of neurotransmitters, such as acetylcholine. Structural and functional alterations in cardiac parasympathetic postganglionic neurons contribute to the withdrawal of cardiac parasympathetic tone, resulting in arrhythmogenesis and sudden cardiac death. This review provides an overview of the remodeling of parasympathetic postganglionic neurons in the ICG, and potential mechanisms contributing to the withdrawal of cardiac parasympathetic tone, ventricular arrhythmogenesis, and sudden cardiac death in T2DM. Improving cardiac parasympathetic tone could be a therapeutic avenue to reduce malignant ventricular arrhythmia and sudden cardiac death, increasing both the lifespan and improving quality of life of T2DM patients.
2 型糖尿病（T2DM）是全球最重要的健康问题之一，到 2045 年，相关医疗保健费用估计将超过 1.054 万亿美元。T2DM 患者的主要死亡原因是心血管疾病（CVD）的发展。在 T2DM 的早期阶段，由于心脏副交感神经活动的丧失，患者会出现心血管自主神经功能障碍。心脏副交感神经张力降低可导致与心律失常相关的心脏性猝死，占 T2DM 患者 CVD 相关死亡的 50%。心血管副交感神经活动的调节是由包括传入、中枢和传出成分在内的多个水平的神经回路整合的。心脏副交感自主神经张力的传出控制是通过位于迷走神经心脏延伸部的节前副交感神经元的活动介导的，节前副交感神经元向位于心脏内神经节（ICG）的节后副交感神经元发出信号。节后副交感神经元通过释放神经递质（如乙酰胆碱）对心脏发挥局部控制作用，而不依赖于大脑高级中枢。心脏副交感节后神经元的结构和功能改变导致心脏副交感神经张力丧失，从而引发心律失常和心脏性猝死。本综述概述了 ICG 中副交感节后神经元的重塑，以及导致 T2DM 中心脏副交感神经张力丧失、室性心律失常发生和心脏性猝死的潜在机制。改善心脏副交感神经张力可能是减少恶性室性心律失常和心脏性猝死的治疗途径，从而延长 T2DM 患者的寿命并提高其生活质量。
