Myocardial infarction reduces cardiac nociceptive neurotransmission through the vagal ganglia

Abstract

Myocardial infarction causes pathological changes in the autonomic nervous system, which exacerbate heart failure and predispose to fatal ventricular arrhythmias and sudden death. These changes are characterized by sympathetic activation and parasympathetic dysfunction (reduced vagal tone). Reasons for the central vagal withdrawal and, specifically, whether myocardial infarction causes changes in cardiac vagal afferent neurotransmission that then affect efferent tone, remain unknown. The objective of this study was to evaluate whether myocardial infarction causes changes in vagal neuronal afferent signaling. Using in-vivo neural recordings from the inferior vagal (nodose) ganglia and immunohistochemical analyses, structural and functional alterations in vagal sensory neurons were characterized in a chronic porcine infarct model and compared with normal animals. Myocardial infarction caused an increase in the number of nociceptive neurons, but a paradoxical decrease in functional nociceptive signaling. No changes in mechanosensitive neurons were observed. Notably, nociceptive neurons demonstrated an increase in GABAergic expression. Given that nociceptive signaling through the vagal ganglia increases efferent vagal tone, the results of this study suggest that a decrease in functional nociception, possibly due to an increase in expression of inhibitory neurotransmitters, may contribute to vagal withdrawal after myocardial infarction.

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“…Myocardial injury is known to cause remodeling of the cardiac autonomic nervous system, leading sympathetic activation and parasympathetic dysfunction ( 1 ). In a chronic porcine infarct model, myocardial infarction was associated with significant functional and structural remodeling of nodose ganglia neurons that transmit cardiac nociceptive signals, reducing cardiac nociceptive neurotransmission ( 13 ). Nodose ganglion degeneration after subarachnoid hemorrhage is associated with coronary vasospasm, and ischemic neurodegeneration of the vagal ganglia can lead to ventricular arrhythmias during subarachnoid hemorrhage ( 14 , 15 ).…”

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“…In the medulla, these afferents synapse upon second-order neurons in the nucleus tractus solitarius (NTS), some of which activate vagal efferent outflow via synapses onto the vagal nuclei in the brain stem [ 2 , 8 ]. No laterality in the territory sensed by vagal afferents has been reported [ 9 ].…”

“…Vagal afferent remodeling in the nodose (vagal) ganglia was studied by Salavatian et al [ 9 ] in a porcine model of chronic myocardial infarction. An increase in the number of nociceptive, but not mechanosensitive, afferents neurons was observed [ 9 ].…”

“…Vagal afferent remodeling in the nodose (vagal) ganglia was studied by Salavatian et al [ 9 ] in a porcine model of chronic myocardial infarction. An increase in the number of nociceptive, but not mechanosensitive, afferents neurons was observed [ 9 ]. Paradoxically, the functional output of these afferent neurons was decreased, and this was associated with an increased expression of the inhibitory neurotransmitter GABA and a decrease in neuronal nitric oxide synthase (nNOS), an afferent neuromodulator with homeostatic properties [ 56 ].…”

“…Paradoxically, the functional output of these afferent neurons was decreased, and this was associated with an increased expression of the inhibitory neurotransmitter GABA and a decrease in neuronal nitric oxide synthase (nNOS), an afferent neuromodulator with homeostatic properties [ 56 ]. In addition, glial fibrillary acidic protein (GFAP) expression by satellite glial cells, a marker of glial activation, was increased [ 9 ]. Collectively, these results indicated extensive structural and functional remodeling of vagal afferent neurons after myocardial infarction that resulted in decreased vagal nociceptive afferent neurotransmission.…”