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 Å) dense-cored vesicles and usually (in various proportions) small “empty” and/or large (900–1500 Å) dense-cored vesicles, (2) a “cholinergic” type containing small (ca. 500 Å) “empty” vesicles and occasionally also some large (mean diameter ca. 1200 Å) 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.