Autonomic innervation of the human cardiac conduction system: Changes frominfancy to senility - An immunohistochemical and histochemical analysis

In order to study the changes in the pattern of autonomic innervation of th e human cardiac conduction system in relation to age, the innervation of th e conduction system of 24 human hearts (the age of the individuals ranged f rom newborn to 80 years), freshly obtained at autopsy, was evaluated by a c ombination of immunofluorescence and histochemical techniques. The pattern of distribution and density of nerves exhibiting immunoreactivity against p rotein gene product 9.5 (PGP), a general neural marker, dopamine P-hydroxyl ase (DBH) and tyrosine hydroxylase (TH), indicators for presumptive sympath etic neural tissue, and those demonstrating positive acetylcholinesterase ( AChE) activity, were studied. All these nerves showed a similar pattern of distribution and developmental changes. The density of innervation, assesse d semiquantitatively, was highest in the sinus node, and exhibited a decrea sing gradient through the atrioventricular node, penetrating and branching bundle, to the bundle branches. Other than a paucity of those showing AChE activity, nerves were present in substantial quantities in infancy. They th en increased in density to a maximum in childhood, at which time the adult pattern was achieved and then gradually decreased in density in the elders to a level similar to or slightly less than that in infancy. In contrast, o nly scattered AChE-positive nerves were found in the sinus and atrioventric ular nodes, but were absent from the bundle branches of the infant heart, w hereas these conduction tissues themselves possessing a substantial amount of pseudocholinesterase. During maturation into adulthood, however, the con duction tissues gradually lost their content of pseudocholinesterase but ac quired a rich supply of AChE-positive nerves, comparable in density to thos e of DBH and TH nerves. The decline in density of AChE-positive nerves in t he conduction tissues in the elders was also similar to those of DBH and TH nerves. Our findings of initial sympathetic dominance in the neural supply to the human cardiac conduction system in infancy, and its gradual transit ion into a sympathetic and parasympathetic codominance in adulthood, correl ate well with the physiologic alterations known to occur in cardiac rate du ring postnatal development. The finding of reduction in density of innervat ion of the conduction tissue with ageing is also in agreement with clinical and electrophysiological findings such as age-associated reduction in card iac response to parasympathetic stimulation. Finally, our findings also sup port the hypothesis that, in addition to the para-arterial route, the paraf ascicular route of extension along the conduction tissue constitutes anothe r pathway for the innervation of the conduction system of the human heart d uring development. Anat Rec 264:169-182, 2001. (C) 2001 Wiley-Liss, Inc.