Fluorescence histochemical and electron-microscopical observations on the innervation of the atrial myocardium of the adult human heart

Abstract

The existence of both adrenergic and cholinergic innervation of the atrial myocardium of the adult human heart was demonstrated by means of fluorescence induced by formaldehyde or glyoxylic acid and by electron microscopy. The adrenergic fluorescing axons (1) followed the course of blood vessels as typical perivascular nerve plexuses, and (2) formed a three-dimensional fairly dense nerve net obviously not related to the blood vessels. The varicosities frequently came into close apposition on myocardial cells. Several types of nerve terminals were differentiated at electron microscopy: (1) an "adrenergic" type containing small (diameter 450-700 A) dense-cored vesicles and usually (in various proportions) small "empty" and/or large (900-1500 A) dense-cored vesicles, (2) a "cholinergic" type containing small (ca. 500 A) "empty" vesicles and occasionally also some large (mean diameter ca. 1200 A) dense-cored vesicles, (3) a "pale" type containing only a few or no vesicles, (4) a "disintegrated" type containing degenerated mitochondria, autophagic vacuoles, and occasional normal-looking mitochondria, (5) nerve terminals containing a large number of mitochondria in addition to varying vesicle populations, and (6) a (possibly baroreceptive type of) nerve terminal containing myelinlike lamellated structures. The "disintegrated" and the "pale" types of nerve terminals possibly represent different stages of axonal degeneration, or may correspond to diminution in the transmitter substance concentration under certain pathophysiologic conditions, respectively. Nerve terminals crowded with mitochondria may be sensory and involved in mechano-or chemoreceptive functions. In preliminary experiments convincing evidence was obtained that the glyoxylic acid-induced fluorescence histochemical method will be suitable for comparative studies on (human) clinical specimens, e.g., for analyzing the degree of the functional activity of the intrinsic adrenergic innervation of the myocardium under various pathophysiologic conditions. The modification which appeared most appropriate for such studies is described in detail, and is proposed for use as a standard method in other similar or related studies on human clinical series. The essential criteria for analyzing the specimens at fluorescence microscopy are suggested as well.

Congruence of adrenergic and cholinergic intrinsic innervation of human and rat atria

“…Furthermore, the present study affords morphological evidence corroborating the view that in the heart, peripheral interactions between the adrenergic and cholinergic nervous systems may be of considerable importance in the neural regulation of the functioning of the organ. This has already been suggested on the basis of ultrastructural observations of cardiac innervation (11,15), but the present study provides a more general concept of the patterns and congruence of innervation, because the methods used permit the mapping of large areas.…”

“…The adrenergic innervation of the myocardium has been studied in both laboratory animals and humans (1,3,5,7,11,16,24,25). Significant alterations may occur in the myocardial catecholamine concentrations and in the inbuilt intrinsic adrenergic nervous system in heart disease (11,14,17,18).…”

“…There obviously exists a definite morphological basis for an autonomous interneuronal link, which might function as an integrating regulative unit at the most peripheral level possible (11). Ultrastructural studies, however, have certain limitations in studies of large specimens for evaluating the degree of congruence of the two main components of the autonomic nervous system.…”

“…These studies have given confirmatory morphological evidence of the existence of adrenergic innervation in the atrial and ventricular myocardium, in the sino-atrial and atrio-ventricular nodes, in the conducting system, in the valves and around blood vessels. Cells containing catecholamines have been observed in the atrial wall, within cholinergic ganglia, and in small clusters of cells considered to be typical paraganglia (1,3,5,7,11,16,24,25). The cholinergic component of innervation has been studied by histochemical demonstration and mapping of acetylcholinesterase (2,4,5,8,10,12,25).…”

“…It is generally assumed that peripheral interaction between the adrenergic and cholinergic nervous systems is of considerable importance in the neural regulation of the organs. Electron microscope studies on the intrinsic cardiac innervation have revealed that different types of nerve terminals are frequently in close apposition without any intervening Schwann cell cytoplasm (11,15,25).…”