Remodeling of stellate ganglion neurons after spatially targeted myocardial infarction: Neuropeptide and morphologic changes

Heart Rhythm. 2015 May;12(5):1027-35. doi: 10.1016/j.hrthm.2015.01.045. Epub 2015 Jan 30.

Abstract

Background: Myocardial infarction (MI) induces remodeling in stellate ganglion neurons (SGNs).

Objective: We investigated whether infarct site has any impact on the laterality of morphologic changes or neuropeptide expression in stellate ganglia.

Methods: Yorkshire pigs underwent left circumflex coronary artery (LCX; n = 6) or right coronary artery (RCA; n = 6) occlusion to create left- and right-sided MI, respectively (control: n = 10). At 5 ± 1 weeks after MI, left and right stellate ganglia (LSG and RSG, respectively) were collected to determine neuronal size, as well as tyrosine hydroxylase (TH) and neuropeptide Y immunoreactivity.

Results: Compared with control, LCX and RCA MIs increased mean neuronal size in the LSG (451 ± 25 vs 650 ± 34 vs 577 ± 55 μm(2), respectively; P = .0012) and RSG (433 ± 22 vs 646 ± 42 vs 530 ± 41 μm(2), respectively; P = .002). TH immunoreactivity was present in the majority of SGNs. Both LCX and RCA MIs were associated with significant decreases in the percentage of TH-negative SGNs, from 2.58% ± 0.2% in controls to 1.26% ± 0.3% and 0.7% ± 0.3% in animals with LCX and RCA MI, respectively, for LSG (P = .001) and from 3.02% ± 0.4% in controls to 1.36% ± 0.3% and 0.68% ± 0.2% in LCX and RCA MI, respectively, for RSG (P = .002). Both TH-negative and TH-positive neurons increased in size after LCX and RCA MI. Neuropeptide Y immunoreactivity was also increased significantly by LCX and RCA MI in both ganglia.

Conclusion: Left- and right-sided MIs equally induced morphologic and neurochemical changes in LSG and RSG neurons, independent of infarct site. These data indicate that afferent signals transduced after MI result in bilateral changes and provide a rationale for bilateral interventions targeting the sympathetic chain for arrhythmia modulation.

Keywords: Autonomic nervous system; Myocardial infarction; Neuronal remodeling; Neuropeptide remodeling; Sympathetic ganglia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Coronary Vessels / pathology
  • Disease Models, Animal
  • Electrocardiography
  • Myocardial Infarction* / etiology
  • Myocardial Infarction* / metabolism
  • Myocardial Infarction* / pathology
  • Neuronal Plasticity*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuropeptide Y / metabolism*
  • Spatial Analysis
  • Stellate Ganglion* / metabolism
  • Stellate Ganglion* / pathology
  • Stellate Ganglion* / physiopathology
  • Swine
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Neuropeptide Y
  • Tyrosine 3-Monooxygenase