Resiniferatoxin-mediated cardiac sympathetic afferent denervation improves post-MI ventricular remodeling and function in dogs

Following a myocardial infarction (MI), autonomic imbalance can severely impair left ventricular (LV) remodeling, contributing to adverse cardiac outcomes. Current standard-of-care often struggles to fully mitigate this imbalance. Ganglionated plexi (GP) are critical nodes in the autonomic nervous system, and their dysfunction is implicated in post-MI pathology. Targeting cardiac sympathetic afferent neurons through interventions like cardiac sympathetic afferent denervation (CSAD) offers a promising strategy to restore autonomic balance and improve cardiac recovery.

This study randomized 31 beagle dogs into three groups: MI group (n=12), CSAD group (n=10), and Control group (n=9, sham surgery). In the CSAD group, Resiniferatoxin (RTX), a neurotoxic TRPV1 antagonist, was injected into the anterior right ganglionated plexi (ARGP) only once. Dogs were followed for 4 weeks post-MI. Primary endpoints included left stellate ganglion (LSG) activity and remodeling, LV dilation, LV function, and levels of inflammatory and neurohormonal biomarkers like hs-CRP, NE, NT-proBNP, and NPY.

After 4 weeks, CSAD treatment in MI dogs led to a significant decrease in left stellate ganglion (LSG) activity and improved LSG remodeling. Critically, the treatment also resulted in reduced LV dilation and improved LV function. This indicates a direct beneficial effect on cardiac mechanics. Furthermore, CSAD treatment significantly attenuated adverse LV remodeling in post-MI LV tissue, suggesting a structural protective effect. The intervention also demonstrated positive modulatory effects on key biomarkers:

CSAD treatment improved levels of high-sensitivity C-reactive protein (hs-CRP), norepinephrine (NE), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and Neuropeptide Y (NPY), all of which are associated with cardiac stress and inflammation.