Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system

Abstract

Key pointsr Intrinsic cardiac (IC) neurons undergo differential morphological and phenotypic remodelling that reflects the site of myocardial infarction (MI).r Afferent neural signals from the infarcted region to IC neurons are attenuated, while those from border and remote regions are preserved post-MI, giving rise to a 'neural sensory border zone' .r Convergent IC local circuit (processing) neurons have enhanced transduction capacity following MI.r Functional network connectivity within the intrinsic cardiac nervous system is reduced post-MI.r MI reduces the response and alters the characteristics of IC neurons to ventricular pacing.Abstract Autonomic dysregulation following myocardial infarction (MI) is an important pathogenic event. The intrinsic cardiac nervous system (ICNS) is a neural network located on the heart that is critically involved in autonomic regulation. The aims of this study were to characterize structural and functional remodelling of the ICNS post-MI in a porcine model (control (n = 16) vs. healed anteroapical MI (n = 16)). In vivo microelectrode recordings of basal activity, as well as responses to afferent and efferent stimuli, were recorded from intrinsic cardiac neurons. From control 118 neurons and from MI animals 102 neurons were functionally classified as afferent, efferent, or convergent (receiving both afferent and efferent inputs). In control and MI, convergent neurons represented the largest subpopulation (47% and 48%, respectively) and had enhanced transduction capacity following MI. Efferent inputs to neurons were maintained post-MI. Afferent inputs were attenuated from the infarcted region (19% in control vs. 7% in MI; P = 0.03), creating a 'neural sensory border zone' , or heterogeneity in afferent information. MI reduced transduction of changes in preload (54% in control vs. 41% in MI; P = 0.05). The overall functional network connectivity, or the ability of neurons to respond to independent pairs of stimuli, within the ICNS was reduced following MI. The neuronal response was differentially decreased to ventricular vs. atrial pacing post-MI (63% in control vs. 44% in MI to ventricular pacing; P < 0.01). MI induced morphological and phenotypic changes within the ICNS. The alteration of afferent neural signals, and remodelling of convergent neurons, represents a 'neural signature' of ischaemic heart disease.

Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction

“…A parasympathetic neuron (classified by its response to right or left VNS) that also responded to an afferent stimulus, including epicardial mechanosensory stimuli and/or changes in preload and afterload, was further classified as a convergent parasympathetic neuron. Convergent neurons are thought to be responsible for the majority of local cardiac neural processing (14,15). A neuron that did not respond to afferent stimuli was classified as an efferent neuron.…”

Pacemaker‐Mediated Programmable Hypertension Control Therapy

“…For example, some studies indicate that long‐term pacing has effects on the balance between sympathetic and parasympathetic activation 14. This may, in part, be related to the effects on the intrinsic cardiac nervous system that is composed of an interconnected network of ganglia and local circuit neurons 15, 16. While it is known that this network communicates with the central nervous system and regulates myocardial properties, less is known about its influence on blood pressure regulation.…”

Programmable Hypertension Control: Another Possible Indication for Implanted Pacemakers

“…The use of short AV delays can also potentially cause a pacemaker syndrome and increased risk of atrial fibrillation and result in sympathoexcitation 16. Indeed pacing the heart results in a neural signature of sympathoexcitation as recorded directly from cardiac neurons 17. Exercise capacity was also not addressed in this study: the putative antihypertensive mechanism of the PHC algorithm, via decreasing cardiac preload and output, could increase fatigue or dyspnea with exertion in physically active patients.…”