Anat Cell Biol.  2019 Mar;52(1):48-56. 10.5115/acb.2019.52.1.48.

Nerve distribution in myocardium including the atrial and ventricular septa in late stage human fetuses

• Cho KH
• Kim JH
• Murakami G
• Abe H
• Rodríguez-Vázquez JF
• Chai OH

• KMID: 2442329
• DOI: http://doi.org/10.5115/acb.2019.52.1.48

Abstract

Few information had been reported on deep intracardiac nerves in the myocardium of late human fetuses such as nerves at the atrial-pulmonary vein junction and in the atrial and ventricular septa. We examined histological sections of the heart obtained from 12 human fetuses at 25-33 weeks. A high density of intracardiac nerves was evident around the mitral valve annulus in contrast to few nerves around the tricuspid annulus. To the crux at the atrioventricular sulcus, the degenerating left common cardinal vein brought abundant nerve bundles coming from cardiac nerves descending along the anterior aspect of the pulmonary trunk. Likewise, nerve bundles in the left atrial nerve fold came from cardiac nerves between the ascending aorta and pulmonary artery. Conversely, another nerves from the venous pole to the atrium seemed to be much limited in number. Moreover, the primary atrial septum contained much fewer nerves than the secondary septum. Therefore, nerve density in the atrial wall varied considerably between sites. As ventricular muscles were degenerated from the luminal side for sculpturing of papillary muscles and trabeculae, deep nerves became exposed to the ventricular endothelium. Likewise, as pectineal muscles were sculptured, nerves were exposed in the atrial endothelium. Consequently, a myocardial assembly or sculpture seemed to be associated with degeneration and reconstruction of early-developed nerves. A failure in reconstruction during further expansion of the left atrium might be connected with an individual variation in anatomical substrates of atrial fibrillation.

Keyword

Heart; Epicardiac nerves; Venous pole; Mitral valve; Atrial septum; Human fetus

MeSH Terms

Aorta
Atrial Fibrillation
Atrial Septum
Endothelium
Fetus*
Heart
Heart Atria
Humans*
Mitral Valve
Muscles
Myocardium*
Papillary Muscles
Phenobarbital
Pulmonary Artery
Sculpture
Veins
Phenobarbital

Figure

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  Fig. 1 Nerves descending between the left atrium (LA) and pulmonary vein to a site along the left common cardinal vein. 25 weeks. Sagittal sections. Immunostaining of S100 protein. Incomplete square in panel A (or B) indicates an area of panel C (or F) at the higher magnification. Ganglia in panel E are shown in panels G and H as well as in an insert at the center of this figure. Panels D and E display intermediate planes between panels C and F. The left pulmonary vein (LPV) drains into the LA in a plane between panels D and E. Abundant nerves around the left common cardinal vein (LCCV in B and F) comes from a superior site (star in B) between the left primary bronchus (BR) and pulmonary artery (PA) via a narrow space between the LPV and LA (arrows in panels A, C–E). AO, aorta; CX, circumflex branch of the left coronary artery; LAU, left auricle; LMT, main trunk of the left coronary artery; LV, left ventricle; RA, right atrium; RCA, right coronary artery; RV, right ventricle; Vagus, left vagus nerve. Scale bars=5 mm (A, B), 1 mm (C–F), 0.1 mm (G, H).

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  Fig. 2 Nerves and ganglia in the left atrial nerve fold and interventricular septum of the heart. 26 weeks. Sagittal sections through the outflow tract of the right ventricle (RV) and the interventricular septum. Hematoxylin and eosin staining (A) and immunostaining of S100 protein (B–E). Squares in panel A are shown in panels B and D at the higher magnification. Panel B shows abundant thin nerves in the interventricular septum: parts of muscular nerves (arrows in E) as well as nerve nets around arteries (arrowheads in E) are exposed to the expanding ventricular endothelium. Panel D as well as panel C (a plane 1 mm left side of D) exhibits the left atrial nerve fold: most of the nerve contents run through the future wall of the pulmonary vein (PV) and they come through a pericardial fold (arrows). An insert between panels B and C displays a ganglion cell (arrow) at the base of the nerve fold. AO, aorta; BR, bronchus; DIA, diaphragm; LA, left atrium; LAU, left auricle; LMT, left main trunk of the coronary artery; LV, left ventricle; PA, pulmonary artery; TH, thymus. Scale bars=5 mm (A), 1 mm (B–D), 0.1 mm (E, insert between B and C).

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  Fig. 3 Nerves and ganglia in the right ventricle and atrium of the heart. 31 weeks. Sagittal sections. Immunostaining of S100 protein. Squares in panel A are shown in panels B–E as well as Fig. 3E at the higher magnification. Panel B displays muscular nerves (arrows) and nerve nets along an artery (arrowheads) in the right ventricular wall. Panel C exhibits the right atrial wall near the orifice of the inferior vena cava (IVC): the ganglia are shown in panels F and G at the higher magnification. Panel D displays a nerve along the endothelium of the superior vena cava (SVC). Panel E shows nerves in the interatrial septum near the orifice of the pulmonary vein. Panel H, a plane 3 mm right of the other panels, exhibits a thick nerve passing through the right auricle (RAU). AZ, azygos vein; BR, bronchus; LA, left atrium; PA, pulmonary artery; RA, right atrium; RV, right ventricle; TH, thymus. Scale bars=5 mm (A), 0.1 mm (B, F, G), 1 mm (C–E, H).

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  Fig. 4 Nerves and ganglia in the interatrial septum and right ventricular wall. 31 weeks. A specimen same as in Fig. 5. Sagittal sections 3 mm medial or left side of Fig. 4. Immunostaining of S100 protein. Squares in panel A are shown in panels B–D and F at the higher magnification. Panel B displays nerves (arrows and arrowheads) in the right ventricular wall: some of them (arrowheads) are exposed to the ventricular endothelium. Panel C exhibits the upper part of the interatrial wall, while panels D and F the lower part. Panel C contains a nerve along the endocardium (arrows) as well as an orifice of a minor cardiac vein draining into left atrium (star). Ganglia near the cavernous sinus (CS) are shown in panel E at the higher magnification. AO, aorta; ES, esophagus; LA, left atrium; PA, pulmonary artery; PD, posterior descending branch of the right coronary artery; RA, right atrium; RAU, right auricle; RV, right ventricle; TH, thymus; TR, trachea. Scale bars=5 mm (A), 1 mm (B–D, F), 0.1 mm (E).

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  Fig. 5 Nerves and ganglia around the atrioventricular valves and in ventricular muscles of the heart. 31 weeks. Sagittal sections through the outflow tract of the right ventricle (RV) and the mitral valve of the left ventricle (LV). Hematoxylin and eosin staining (A) and immunostaining of S100 protein (B–G). Squares in panel A are shown in panels B, C, F and G at the higher magnification. Panels B–D display nerves around the mitral valve annulus. Panel D shows a plane 0.5 mm left side of panel C. An insert between panels A and B displays ganglion cells (arrows) near the base of the mitral valve. Panel E exhibits the tricuspid valve of the same specimen (corresponding to a square in Fig. 4A). In contrast to abundant nerves around the mitral valve annulus (B–D), few nerves are seen around the tricuspid valve annulus (E). Panel F shows muscular nerves (arrows) in trabeculae of the RV: parts of them are exposed to the expanding ventricular endothelium. Panel G displays a nerve net (arrowheads) along an artery in the papillary muscle of the LV. LA, left atrium; LMT, left main trunk of the coronary artery; PA, pulmonary artery; PV, pulmonary vein; RA, right atrium. Scale bars=5 mm (A), 1 mm (B–E), 0.1 mm (F, G, insert between A and B).

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  Fig. 6 Nerves and ganglia along the coronary sulcus of the heart. 30 weeks. Sagittal section through the aortic outflow tract of the left ventricle (LV) as well as the mitral valve. Immunostaining of S100 protein. Two squares in panel A are shown in panels B and D at the higher magnification. A ganglion in panel B or D is shown in panel C or D at the higher magnification. The left common cardinal vein (LCCV) is degenerating and obliterated in a plane 3 mm left of panel B, but it accompanies abundant nerves (B). AD, anterior descending branch of the left coronary artery; AO, aorta; BR, bronchus; CS, coronary sinus; DA, ductus arteriosus; DIA, diaphragm; LA, left atrium; LAU, left auricle; LPA, left pulmonary artery; PA, pulmonary artery. Scale bars=5 mm (A), 1 mm (B, D), 0.1 mm (C, E).

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