Background: Premature ventricular contractions (PVCs) stress the autonomic nervous system. Cardiac TRPV1 afferent fibers are implicated in the reflex processing of cardiac stress, however, their role in PIC is unknown.
Objective: We aimed to examine whether TRPV1 afferent fibers promote PIC.
Methods: A PIC swine model (50% PVC burden) was created via an implanted pacemaker (PPM). Animals were randomized to sham (n=5), PVC only (n=8), or PVC + percutaneous epicardial application of resiniferatoxin (RTX), a toxic activator of the TRPV1 channel, depleting cardiac sensory afferents (PVC+RTX; n=7). Echocardiography was performed before, and at 4- and 9-weeks after PPM implantation. Hemodynamics, autonomic function and immunohistochemical (IHC) staining data were examined at 9-week terminal studies.
Results: Depletion of Cardiac TRPV1 afferents by RTX was confirmed by IHC and functional responses to TRPV1 activators. Baseline LVEF was similar across groups, however, at 4weeks, LVEF was lower in the PVC vs. PVC+RTX group (45.0±2.1% vs. 51.7±1.6%, respectively (p=0.030)). At 9weeks LVEF was 33.5±1.8% and 34.6±1.8% (p=0.589), respectively. The PVC group also showed a larger LV systolic dimension (LVDs) (p=0.026) compared to PVC+RTX subjects at 4 but not 9 weeks. At terminal studies, basal heart rate (HR) and blood pressure were similar in all groups. HR response to vagal nerve stimulation in control, PVC and PVC+RTX group were -23.2±6.9%, -27.0±5.2% and -29.1±5.2% (p=0.759), and to stellate ganglion stimulation were +94.7±11.9%, +80.9±20.7% and +72.0±13.1% (p=0.442), respectively.IHC analyses showed no significant differences between the 3 groups in the percentage of adrenergic neurons (TH positive), while the percentage of cholinergic neuron (VACHT positive) in control, PVC and PVC+RTX group were 7.7±1.3%, 14.4±1.0% and 13.9±0.9% (p=0.013), respectively, suggesting adrenergic to cholinergic transdifferentiation in PIC.
Conclusion: Cardiac TRPV1 afferent fibers contribute to early but not to late stages of PIC. Adrenergic to cholinergic transdifferentiation is a feature of autonomic remodeling in PIC.