Pathological effects of chronic myocardial infarction on peripheral neurons mediating cardiac neurotransmission

• Published in: Autonomic neuroscience Vol. 197; pp. 34 - 40
• Main Authors: Nakamura, Keijiro, Ajijola, Olujimi A., Aliotta, Eric, Armour, J. Andrew, Ardell, Jeffrey L., Shivkumar, Kalyanam
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2016
• Subjects: Advanced Basic Science; Animals; Autonomic nervous system; Calcitonin Gene-Related Peptide - metabolism; CGRP; Chronic Disease; Chronic myocardial infarction; Dorsal root ganglia; Ganglia, Spinal - metabolism; Intrinsic cardiac nervous system; Medical Education; Myocardial Infarction - metabolism; Neurons - metabolism; Nitric Oxide Synthase Type I - metabolism; nNOS; Stellate ganglion; Stellate Ganglion - metabolism; Swine; Synaptic Transmission - physiology; MRI; ANS; ECG; LV; VIV GP; IV; LAD; RVOT; Dorsal root ganglia; SG; Stellate ganglion; Autonomic nervous system; LCN; Intrinsic cardiac nervous system; nNOS; DRG; MI; Chronic myocardial infarction; ICNS; CGRP; magnetic resonance imaging; myocardial infarction; left anterior descending coronary artery; right ventricular outflow tract; stellate ganglion; electrocardiogram; intravenous; left ventricle/ventricular; autonomic nervous system; intrinsic cardiac nervous system; ventral interventricular ganglionated plexus; dorsal root ganglion; local circuit neuron
• ISSN: 1566-0702; 1872-7484; 1872-7484
• DOI: 10.1016/j.autneu.2016.05.001

To determine whether chronic myocardial infarction (MI) induces structural and neurochemical changes in neurons within afferent and efferent ganglia mediating cardiac neurotransmission. Neuronal somata in i) right atrial (RAGP) and ii) ventral interventricular ganglionated plexi (VIVGP), iii) stellate ganglia (SG) and iv) T1–2 dorsal root ganglia (DRG) bilaterally derived from normal (n=8) vs. chronic MI (n=8) porcine subjects were studied. We examined whether the morphology and neuronal nitric oxide synthase (nNOS) expression in soma of RAGP, VIVGP, DRG and SG neurons were altered as a consequence of chronic MI. In DRG, we also examined immunoreactivity of calcitonin gene related peptide (CGRP), a marker of afferent neurons. Chronic MI increased neuronal size and nNOS immunoreactivity in VIVGP (but not RAGP), as well as in the SG bilaterally. Across these ganglia, the increase in neuronal size was more pronounced in nNOS immunoreactive neurons. In the DRG, chronic MI also caused neuronal enlargement, and increased CGRP immunoreactivity. Further, DRG neurons expressing both nNOS and CGRP were increased in MI animals compared to controls, and represented a shift from double negative neurons. Chronic MI impacts diverse elements within the peripheral cardiac neuraxis. That chronic MI imposes such widespread, diverse remodeling of the peripheral cardiac neuraxis must be taken into consideration when contemplating neuronal regulation of the ischemic heart.