title: Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system.
abstract: CONCLUSIONS
  Intrinsic cardiac (IC) neurons undergo differential morphological and phenotypic remodelling that reflects the site of myocardial infarction (MI). 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'. Convergent IC local circuit (processing) neurons have enhanced transduction capacity following MI. Functional network connectivity within the intrinsic cardiac nervous system is reduced post-MI. MI reduces the response and alters the characteristics of IC neurons to ventricular pacing.
  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.
authors.affiliation: University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, CA, USA.|Neurocardiology Research Center of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Molecular, Cellular & Integrative Physiology Program, UCLA, Los Angeles, CA, USA.
authors.forename: Pradeep S
authors.initials: PS
authors.lastname: Rajendran
authors.affiliation: University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, CA, USA.|Neurocardiology Research Center of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, CA, USA.|Neurocardiology Research Center of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Olujimi A
authors.initials: OA
authors.lastname: Ajijola
authors.affiliation: University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, CA, USA.|Neurocardiology Research Center of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Molecular, Cellular & Integrative Physiology Program, UCLA, Los Angeles, CA, USA.
authors.forename: Marmar
authors.initials: M
authors.lastname: Vaseghi
authors.affiliation: University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, CA, USA.|Neurocardiology Research Center of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Armour
authors.affiliation: University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, CA, USA.|Neurocardiology Research Center of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Molecular, Cellular & Integrative Physiology Program, UCLA, Los Angeles, CA, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ardell
authors.affiliation: University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, CA, USA.|Neurocardiology Research Center of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.|Molecular, Cellular & Integrative Physiology Program, UCLA, Los Angeles, CA, USA.
authors.forename: Kalyanam
authors.initials: K
authors.lastname: Shivkumar
mesh_terms: D000200:Action Potentials; D000818:Animals; D001341:Autonomic Nervous System / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000294:innervation; D006339:Heart Rate; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D013552:Swine