Introduction: Mechanisms behind parasympathetic withdrawal due to myocardial infarction (MI) are unknown. Afferent neurons in the inferior vagal (nodose) ganglia transduce cardiac function beat by beat and transmit information from the heart to the brainstem, which then modulates parasympathetic output.
Hypothesis: We hypothesized that MI causes structural and functional changes in nodose cardiac neurons, leading to parasympathetic withdrawal.
Methods: Right and left nodose ganglia neurons from normal (n=9) and chronic right and left anterior descending coronary artery MI (n=20) pigs were analyzed for expression of neurotransmitters/peptides known to be important in cardiac neural transmission, including neuronal nitric oxide synthase (nNOS), calcitonin gene related peptide (CGRP), and tyrosine hydroxylase (TH). Using in-vivo nodose ganglia recordings in 6 normal and 4 MI animals, 36 cardiac afferent neurons were identified based on their response to cardiac interventions: mechanical stimuli, application of adenosine, inferior vena cava and aortic occlusion, and premature ventricular contractions. Basal activity of neurons was evaluated in normal vs. infarcted pigs.
Results: 1756±796 neurons in normal and 1560±756 neurons in MI animals were analyzed. Percentage of TH and CGRP positive neurons increased in infarcted vs. normal animals (2.2±2.9% vs. 5.7±3.2%, P<0.01; 8.3±5.1% vs. 24.5±14%, P<0.01, respectively), as did neuronal size (1201±124 vs. 1380±223 μm2, P=0.02), while percentage of nNOS positive neurons significantly decreased (35±17% vs. 21±10%, P=0.01). Cardiac afferent neurons showed significantly lower basal firing frequency in infarcted vs. normal pigs (0.21±0.1 vs. 0.94±0.3 Hz, p<0.02).
Conclusion: Pathological structural and functional remodeling in the inferior vagal ganglia occurs in the setting of MI. This novel finding sheds light on neural changes that could be contributing to central parasympathetic withdrawal.