Sympathetic nociceptive afferent signaling drives the chronic structural and functional autonomic remodeling after myocardial infarction

Van Weperen, V.; Hoang, J. D.; Jani, N.; Atmani, K.; Chan, C. A.; Cao, K.; Avasthi, S.; Lokhandwala, Z. A.; Emamimeybodi, M.; Vaseghi, M.

doi:10.1101/2025.03.28.645120

bioRxiv · 10.1101/2025.03.28.645120

Sympathetic nociceptive afferent signaling drives the chronic structural and functional autonomic remodeling after myocardial infarction

Van Weperen, V.·Hoang, J. D.·Jani, N.·Atmani, K.·Chan, C. A.·Cao, K.·Avasthi, S.·Lokhandwala, Z. A.·Emamimeybodi, M.·Vaseghi, M.

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Abstract

After chronic myocardial infarction (MI), pathological autonomic remodeling, including vagal dysfunction and sympathoexcitation, predisposes to ventricular arrhythmias (VT/VF). However, what underlies this functional and structural remodeling remains unknown. We hypothesized that sympathetic nociceptive afferent signaling initiates and perpetuates these pathological autonomic changes. We employ cervicothoracic epidural resiniferatoxin (RTX) to ablate spinal nociceptive neurons in male pigs before MI, and assessed autonomic and electrophysiological function four-to-six weeks post-infarction. Compared to vehicle-treated infarcted animals, epidural RTX attenuates the loss of vagal tone and baroreflex sensitivity, reduces spinal cord inflammation, glial activation, and circulating stress and inflammatory markers, and stabilizes electrophysiological parameters, lowering VT/VF inducibility. In a separate cohort, acute C7-T1 nociceptive afferent ablation after chronic MI acutely restores vagal function and decreases VT/VF inducibility. This study demonstrates that cervicothoracic spinal nociceptive afferents significantly contribute to MI-induced autonomic remodeling and VT/VF, providing novel insight into the mechanisms underlying sympathovagal imbalance after MI.

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Van Weperen, V., Hoang, J. D., Jani, N., Atmani, K., Chan, C. A., Cao, K., Avasthi, S., Lokhandwala, Z. A., Emamimeybodi, M., Vaseghi, M.. 2025-03-28. Sympathetic nociceptive afferent signaling drives the chronic structural and functional autonomic remodeling after myocardial infarction. https://doi.org/10.1101/2025.03.28.645120

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