Distribution of adrenergic and cholinergic nerve fibres within intrinsic nerves at the level of the human heart hilum

Eur J Cardiothorac Surg. 2014 Jun;45(6):1097-105. doi: 10.1093/ejcts/ezt575. Epub 2013 Dec 12.


Objectives: The disbalance between adrenergic (sympathetic) and cholinergic (parasympathetic) cardiac inputs facilitates cardiac arrhythmias, including the lethal ones. In spite of the fact that the morphological pattern of the epicardiac ganglionated subplexuses (ENsubP) has been previously described in detail, the distribution of functionally distinct axons in human intrinsic nerves was not investigated thus far. Therefore, the aim of the present study was to quantitatively evaluate the distribution of tyrosine hydroxylase (TH)- and choline acetyltransferase (ChAT)-positive axons within intrinsic nerves at the level of the human heart hilum (HH), since they are of pivotal importance for determining proper treatment options for different arrhythmias.

Methods: Tissue samples containing the intrinsic nerves from seven epicardiac subplexuses were obtained from nine human hearts without cardiac pathology and processed for immunofluorescent detection of TH and ChAT. The nerve area was measured and the numbers of axons were counted using microphotographs of nerve profiles. The densities of fibres were extrapolated and compared between subplexuses.

Results: ChAT-immunoreactive (IR) fibres were evidently predominant (>56%) in nerves of dorsal (DRA) and ventral right atrial (VRA) ENsubP. Within both left (LC) and right coronary ENsubP, the most abundant (70.9 and 83.0%, respectively) were TH-IR axons. Despite subplexal dependence, ChAT-IR fibres prevailed in comparatively thinner nerves, whereas TH-IR fibres in thicker ones. Morphometry showed that at the level of HH: (i) LC subplexal nerves were found to be the thickest (25 737 ± 4131 μm(2)) ones, whereas the thinnest (2604 ± 213 μm(2)) nerves concentrated in DRA ENsubP; (ii) the density of ChAT-IR axons was highest (6.8 ± 0.6/100 μm(2)) in the ventral left atrial nerves and lowest (3.2 ± 0.1/100 μm(2)) in left dorsal ENsubP and (iii) the density of TH-IR fibres was highest (15.9 ± 2.1/100 μm(2)) in LC subplexal nerves and lowest (4.4 ± 0.3/100 μm(2)) in VRA nerves.

Conclusions: (i) The principal intrinsic adrenergic neural pathways in the human heart proceed via both coronary ENsubP that supply cardiac ventricles and (ii) the majority of cholinergic nerve fibres access the human heart through DRA and VRA ENsubP and extend towards the right atrium, including the region of the sinuatrial node.

Keywords: Human heart hilum; Immunohistochemistry for tyrosine hydroxylase and choline acetyltransferase; Intrinsic cardiac nerves.

MeSH terms

  • Adrenergic Neurons / chemistry*
  • Adult
  • Aged
  • Analysis of Variance
  • Choline O-Acetyltransferase / chemistry
  • Cholinergic Neurons / chemistry*
  • Female
  • Heart / innervation*
  • Histocytochemistry
  • Humans
  • Male
  • Middle Aged
  • Myocardium / chemistry*
  • Nerve Fibers / chemistry*
  • Photomicrography
  • Tyrosine 3-Monooxygenase / chemistry


  • Tyrosine 3-Monooxygenase
  • Choline O-Acetyltransferase