Abstract Body: Background
Ventricular arrhythmias (VT/VF), the most common cause of sudden death after myocardial infarction (MI), can be ameliorated by cardiac-selective transient receptor potential cation channel subfamily V member 1 (TRPV1) afferent ablation at the time of infarction in animal models. To enable translation to human, it remains unknown whether afferent depletion in the subacute phase of MI will reduce arrhythmias and mitigate long-term structural remodeling.

Objectives
To assess the role of cardiac-selective TRPV1 afferent ablation two weeks after MI on the long-term ventricular arrhythmogenesis and adverse structural remodeling.

Methods
Yorkshire pigs were randomized to resiniferatoxin (RTX 5.0µg/ml: n=10) or vehicle(n=6) 14days after the left anterior descending artery infarct. Four weeks later, terminal experiments were conducted to evaluate the effect of RTX on cardiac structural and functional remodeling, ventricular arrhythmogenesis, and autonomic reflex function.

Results
Cardiac afferent depletion via RTX administration was confirmed by diminished sympathetic response to TRPV1 agonists (bradykinin and capsaicin) and by immunohistochemical analysis of ventricular innervation.
Compared to the vehicle treated group, the RTX administration reduced LV dimension (p<0.01), repolarization heterogeneity (p<0.01) and ventricular arrhythmogenesis (program stimulation; p=0.01 and CsCl induced PVCs;p<0.01).
In the scar-border zone, myocytolysis and nerve sprouting, which are associated with VT/VF, were attenuated in the RTX group (abnormality score; p=0.01 and nerve sprouting index; p < 0.01). T cell infiltration in dorsal root ganglia was suppressed in the RTX group (p = 0.02). RNA-sequencing of stellate ganglia revealed downregulation of adrenergic genes tyrosine hydroxylase and neuropeptide-Y in the RTX group.
Taken together, these results suggest that cardiac afferent ablation in subacute MI alleviates adverse structural remodeling and ventricular arrhythmogenesis by targeting neuroinflammation and reducing stellate ganglion sympathetic overexcitation.

Conclusion
Cardiac TRPV1 afferent depletion in subacute MI is a promising disease altering treatment for patients suffering from MI.