Although cardiac autonomic markers are commonly used to assess cardiac reinnervation in heart transplant patients (HTx), their relationship to the degree of sympathetic and vagal cardiac reinnervation is not well understood yet. To study this relationship, we applied a mathematical model of the cardiovascular system and its autonomic control. By simulating varying levels of sympathetic and vagal efferent sinoatrial reinnervation, we analyzed the induced changes in cardiac autonomic markers including resting heart rate (HR), bradycardic and tachycardic HR response to Valsalva Maneuver, root mean square of successive differences between normal heartbeats (RMSSD), low-frequency- (LF), high-frequency- (HF), and total spectral power. The results suggest that for assessment of vagal cardiac reinnervation levels >20%, resting HR (=0.99, p<0.05), RMSSD (=0.97, p<0.05), and total spectral power (=0.96, p<0.05) may be equally suitable as the commonly used measure of HF-power (=0.97, p<0.05). To assess sympathetic reinnervation, our results suggest that the LF/HF-ratio (=0.87, p<0.05) and tachycardic response to Valsalva maneuver (=0.9, p<0.05) may be more suitable than the regularly used measure of LF-power (=0.77, p<0.05). Our model reports, for the first time, mechanistic relationships between the cardiac autonomic markers and the level of efferent autonomic sinoatrial reinnervation. The results indicate differences in the suitability of these markers to assess vagal and sympathetic reinnervation. Although our analysis is purely conceptual yet, the developed mathematical model can help to gain important insights into the genesis of cardiac autonomic markers and their relationship to efferent sinoatrial reinnervation and, thus, provide indications for clinical study evaluation.

中文翻译：

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从心脏自主标记解码心脏神经再支配：数学模型方法

尽管心脏自主标记物通常用于评估心脏移植患者（HTx）的心脏再神经支配，但它们与交感神经和迷走神经心脏再神经支配程度的关系尚不清楚。为了研究这种关系，我们应用了心血管系统及其自主控制的数学模型。通过模拟不同水平的交感神经和迷走神经传出窦房再神经支配，我们分析了心脏自主标志物的诱发变化，包括静息心率 (HR)、对瓦尔萨尔瓦动作的心动过缓和心动过速 HR 反应、正常心跳之间的连续差均方根 (RMSSD) 、低频 (LF)、高频 (HF) 和总频谱功率。结果表明，为了评估迷走心脏神经支配水平 >20%，静息 HR（=0.99，p<0.05）、RMSSD（=0.97，p<0.05）和总频谱功率（=0.96，p<0.05）可能是同样适合作为常用的高频功率测量（=0.97，p<0.05）。为了评估交感神经支配，我们的结果表明低频/高频比（=0.87，p<0.05）和瓦尔萨尔瓦动作的心动过速反应（=0.9，p<0.05）可能比常规使用的低频功率测量更合适(=0.77，p<0.05)。我们的模型首次报告了心脏自主标记物与​​传出自主神经窦房神经支配水平之间的机制关系。结果表明这些标记物评估迷走神经和交感神经支配的适用性存在差异。尽管我们的分析纯粹是概念性的，但开发的数学模型可以帮助深入了解心脏自主标记物的起源及其与传出窦房神经支配的关系，从而为临床研究评估提供指示。