Autonomic nervous system modulation in arrhythmias: mechanisms and therapeutic advances

Figures

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  Figure 1. Abnormalities of the autonomic nervous system. In the infarct border zone, nerve regeneration occurs and the density of sympathetic nerve fibers increases. But in the central infarct zone, nerves degenerate and the growth of sympathetic nerve axons are inhibited. This process results in disparities in nerve density between different regions of the heart. Myocardial infarction induces transient cholinergic transdifferentiation of cardiac sympathetic nerves via the gp130 and JAK-STAT signaling pathway. Leptin activates the JAK2-STAT3 pathway in sympathetic neurons via its receptor, upregulates SOCS3 through feedback inhibition, and ultimately leads to substantial neuronal release of NPY. NPY then acts on the Y1 receptor, enhancing NCX activity and activating CaMKII. Figure created with BioRender.com.

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  Figure 2. The immunological mechanisms underlying arrhythmias induced by autonomic nervous system dysregulation. Following myocardial infarction, microRNA-155 promotes M1 macrophage polarization and inflammatory responses by targeting and inhibiting SOCS1, thereby activating the NF-κB pathway. This leads to increased expression of NGF, which in turn induces sympathetic neural remodeling and Vas. The activation of the NGF/TrkA signaling pathway and the release of pro-inflammatory cytokines upregulate the expression of TH in neurons, indicating a marked enhancement in their capacity to synthesize and release NE. Concurrently, increased expression of GAP43 reflects active nerve regeneration. NGF signaling further participates in the regulation of neuropeptide synthesis, leading to elevated production of calcitonin gene-related peptide (CGRP) and substance P (SP). These neuropeptides act directly on the local immune milieu, recruiting and activating macrophages, promoting mast cell degranulation, and thereby exacerbating cardiac local inflammation. In addition, the P2X7 receptor contributes to the pathological process of post-myocardial infarction sympathetic nerve sprouting by activating the…

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  Figure 3. Neuroscientific interventions for cardiac arrhythmia and the targets of autonomic modulation therapy. Figure created with BioRender.com.