An immunohistochemical analysis of the autonomic innervation of the human heart

The objective of the present investigation is to study the change in pattern of innervation of the human heart, with emphasis on that of the cardiac conduction system, from infancy to senility, employing a combination of immunohistochemical and histochemical techniques.;Twenty-four human hearts were taken at necropsy, within 18 hours of death, from individuals without congenital cardiac anomalies and dying from causes unrelated to the heart. Their age ranged from newborn to 80 years. The antibodies employed included those against protein gene product 9.5 (PGP) as a sensitive marker for neural tissue, dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) to reveal catecholaminergic neural tissue, and neuropeptide Y (NPY). A histochemical technique was used to reveal tissue cholinesterase activity.;Abundant PGP nerves were seen in the atrial myocardium, forming perivascular plexuses and lying in close apposition to myocardial cells. Both DBH and TH nerves showed a similar pattern of distribution as that of PGP nerves; in the atria, their densities were approximately half that of PGP nerves, while in the ventricles, the densities of DBH and TH nerves were similar to that of PGP nerves. Relatively fewer NPY nerves were observed in both the atrial and ventricular myocardium. The density of AChE-positive nerves in the atria was again approximately half that of PGP nerves, whereas in the ventricles, they were extremely sparse.;For nerves showing immunoreactivity against PGP, DBH, TH and NPY, as well as those showing positive AChF activity, all showed a similar pattern of distribution and developmental changes.;Our findings of initial sympathetic dominance in the neural supply to the human cardiac conduction system in infancy, and its gradual transition into a sympathetic and parasympathetic co-dominance in adulthood, correlate well with the physiologic alterations known to occur in cardiac rate during postnatal development. The finding of reduction in the density of innervation of the conduction tissue with aging is also in agreement with clinical and electrophysiological findings such as the age-associated reduction in cardiac response to parasympathetic stimulation. Finally, our findings also support the hypothesis that, in addition to the para-arterial route, the parafascicular route of extension along the conduction tissue constitutes the alternative pathway for the innervation of the conduction system of the human heart during development. (Abstract shortened by UMI.).