Introduction

Most of the anatomical research on the cardiac autonomic nerve system has been fragmentary because of the long course from the origin to the target. Therefore, most macroscopic anatomical studies on autonomic cardiac nerves have been limited to either the sympathetic or parasympathetic nervous systems only. Studies on sympathetic nerves have usually been divided into two types: research on the proximal part from the spinal nerves to the sympathetic ganglia (Axford 1927–1928; Becker and Grunt 1957; Harman 1900; Hoffman 1957; Jamieson et al. 1952; Kuntz 1946; Mitchell 1953; Pick and Sheehan 1946; White and Smithwick 1952; Wrete 1959) and research on the distal part from the sympathetic ganglia to the visceral nerves (Ellison and Williams 1962; Fukuyama 1982; Hausmann 1956; Janes et al. 1986; Kuntz and Morehouse 1930; Mizeres 1963; Mitchell 1953; Pick 1970). Dissecting the entire course from origin to peripheral distribution seems to have been difficult.

Until now, comparative anatomical studies on the entire sympathetic cardiac nerve have been performed to clarify the efferent pathway from the spinal cord to the heart (Kawashima et al. 2000, 2001), in addition to contributing to cardiovascular research (Kawashima et al. 2003a, 2003b, 2004, 2005).

Therefore, in this study I attempted a submacroscopic anatomical investigation to clarify the detailed morphology of the entire autonomic cardiac nerves, including both sympathetic and parasympathetic nerves, by examining human cadavers using a binocular microscope.

Materials and methods

A submacroscopic anatomical analysis was performed to identify the origin, course, and peripheral distribution of the autonomic nerves to the heart using 36 sides of 18 embalmed adult human cadavers under a stereomicroscope. All cadavers were fixed by 10% formalin solution and preserved in 30% ethyl alcohol over 1 year, as well as being subjected to normal Japanese embalming procedures for student anatomical practice. Cadavers with clearly abnormal hearts and/or surrounding vessels were excluded from the analysis.

Decalcifying method

On six sides of three bodies, the relationships between the vertebral nerves and the spinal nerves were examined after decarbonization using the Plank-Rychlo solution (0.3 M aluminum chloride, 3% HCl, and 5% formic acid; Plank and Rychlo 1952) for 2 weeks. This solution is commonly used for decalcification in many laboratories. After decalcification, the specimens were decalcified with inorganic acid (10% nitric acid, 10% HCl, and K-CX solution) and neutralized by sodium sulfate for 12 h.

Staining method

The intrapericardium peripheral autonomic nerve distribution to the heart was examined using Sudan black stain. After careful examination of the origin and course of the autonomic cardiac nervous system, hearts with autonomic nerves were removed from the bodies. The specimens were kept overnight at room temperature in Sudan black solution (Sudan black B [Wako Pure Chemical, Japan] 5 g and 70% ethyl alcohol to make 1,000 ml).

Observation method

All dissections were examined under a stereomicroscope for operation (Olympus OME 5000). Major stages were recorded in detailed step-by-step drawings of lateral aspects in addition to the ventral aspect in order to preserve the relationships among the vessels, the nerves, and the surrounding structures. Consecutive dissection steps were documented by digital images using a Nikon digital camera.

The protocol for the present research did not include any specific issue requiring approval from the university ethics committees. The present work conformed to the provisions of the 1995 Declaration of Helsinki (revised in Edinburgh 2000).

Results

Sympathetic ganglia

The superior cervical ganglion was observed in all cases (100%), the middle cervical ganglion was observed on 33 sides (91.7%), and the vertebral ganglion was observed on 34 sides (94.4%). In addition, the accessory middle cervical ganglion and the fusion ganglion between the middle cervical and the vertebral ganglia were observed on 11 sides (30.6%) and on 2 sides (5.6%), respectively.

A single inferior cervical ganglion without fusion to the thoracic ganglia was present on 5 sides (13.9%, Fig. 1a), whereas most cases exhibited a cervicothoracic (stellate) ganglion (31 sides, 86.1%). The cervicothoracic ganglion was composed of the inferior cervical and the 1st thoracic ganglia on 30 sides (83.3%) and the inferior cervical, the 1st thoracic, and the 2nd thoracic ganglia on one side (2.8%).

Fig. 1
figure 1

Photographs showing the autonomic nervous system distribution to the heart and surrounding great vessels. a Composition of the sympathetic ganglia innervating the heart, as viewed from the right side (no. 1). b The cardiac nerves descending along the great vessels on the right side. c Regional enlargement of b. Asterisks show the autonomic cardiac nerves. [AI anterior interventricular branch, Ao aorta, Az azygos vein, CB circumflex branch, CC common carotid artery, CT cervicothoracic (stellate) ganglion, GV great cardiac vein, IB inferior (vagal) cardiac branch, IG inferior cervical ganglion, IN inferior cervical cardiac nerve, L lung, LA left atrium, LCA left coronary artery, MG middle cervical ganglion, MN middle cardiac nerve, P pectoral nerve, Ph phrenic nerve, PT pulmonary trunk, RA right atrium, RCA right coronary artery, RL recurrent laryngeal nerve of vagus nerve, SB superior (vagal) cardiac branch, Sbc nerve to subclavian muscle, SG superior cervical ganglion, SN superior cardiac nerve, SS suprascapular nerve, SVC superior vena cava, TB thoracic (vagal) cardiac branch, TG thoracic ganglia, TN thoracic cardiac nerve, VG vertebral ganglion, VN vertebral nerve, X vagus nerve, XI accessory nerve, XII hypoglossal nerve]

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The superior cervical ganglion was consistently positioned behind (medial) the bifurcation of the common carotid artery and between the 1st to 3rd cervical vertebrae, whereas the position of the middle cervical ganglion varied, being located in various portions of the sympathetic trunk between the 3rd and 7th cervical vertebrae. The vertebral ganglion was usually positioned on the ventral surface of the vertebral artery, usually joining between the anterior (ventral) and posterior (dorsal) roots of the ansa subclavius. The cervicothoracic ganglion was positioned between the 7th cervical and the 1st thoracic vertebrae, depending on the composition of the thoracic ganglia.

Communicating branches between sympathetic ganglia and spinal nerves

The superior cervical ganglion exhibited communicating branches with the spinal nerves on all sides (100%), communicating with the 1st cervical nerve (C1, 100%), C2 (100%), C3 (26/36 sides, 72.2%), and C4 (1/36 sides, 2.8%).

The middle cervical ganglion, observed on 33 sides, had communicating branches with the spinal nerves on 32 sides (97%), communicating with C3 (11/33 sides, 33.3%), C4 (29/33 sides, 87.9%), C5 (20/33 sides, 60.6%), and C6 (5/33 sides, 15.2%).

The vertebral ganglion, observed on 34 sides, had communicating branches with the spinal nerves on 10 sides (29.4%), communicating with C4 (1/10 sides, 10%), C5 (2/10 sides, 20%), C6 (3/10 sides, 30%), and C7 (6/10 sides, 60%).

The inferior cervical or the cervicothoracic ganglia had communicating branches with the spinal nerves on all sides (100%), communicating with C5 (2/36 sides, 5.6%), C6 (4/36 sides, 11.1%), C7 (27/36 sides, 75%), C8 (36/36 sides, 100%), T1 (36/36 sides, 100%), T2 (25/36 sides, 69.4%), and T3 (1/36 side, 2.8%). The ganglion communicating with T3 was a cervicothoracic ganglion composed of the inferior cervical, the 1st thoracic, and the 2nd thoracic ganglia.

Vertebral nerve

The vertebral nerve consisted of the nerve following the vertebral artery and entering into the foramen transversarium; a variety of origins for this nerve were observed.

None of the observed vertebral nerves originated from the middle cervical ganglion. However, one vertebral nerve originating from the fusion ganglion of the middle cervical and the vertebral ganglia was observed on one side, vertebral nerves from the vertebral ganglion on 26/34 sides (76.5%), and vertebral nerves from the inferior cervical or cervicothoracic ganglia on 34/36 sides (94.4%).

Next, the course of the vertebral nerve was traced by removing the bony elements after decarbonization on six sides of three necks. A peripheral nerve distribution analysis showed that the vertebral nerve communicated with the spinal nerves: with C5 (3/6 sides, 50%), C6 (6/6 sides, 100%), and C7 (6/6 sides, 100%).

Sympathetic cardiac nerves arising from sympathetic ganglia and trunk

In the present study, cardiac nerves were regarded as nerves with direct connections or connections via the cardiac plexus. Each cardiac nerve was named according to its origin as follows: superior cardiac nerves arose from the superior cervical ganglion and the sympathetic trunk between the superior and the middle cervical ganglia; middle cardiac nerves arose from the (accessory) middle cervical, the vertebral ganglia, and the sympathetic trunk between the middle and the inferior cervical ganglia, including the ansa subclavius; inferior cardiac nerves arose from the inferior cervical or the cervicothoracic ganglia; and thoracic cardiac nerves arose from the thoracic ganglia and the thoracic sympathetic trunk below the inferior cervical or the cervicothoracic ganglia.

The superior cardiac nerve originating from the superior cervical ganglion was observed on 32/36 sides (88.9%; 15 right sides, 17 left sides) and from the sympathetic trunk between the superior and the middle cervical ganglia on 25 sides (69.4%; 11 right sides, 14 left sides).

The middle cardiac nerve originating from the middle cervical ganglion was observed on 29/33 sides (87.8%; 13 right sides, 16 left sides), from the vertebral ganglion on 27/34 sides (79.4%; 15 right sides, 12 left sides), from the ansa subclavicla on 16/36 sides (44.4%; six right sides, 12 left sides), and from the sympathetic trunk between the middle and the inferior cervical ganglia on 10/36 sides (27.8%; four right sides, six left sides).

The inferior cardiac nerve originating from the inferior cervical or the cervicothoracic ganglia was observed on 27/36 sides (75%; 14 right sides, 13 left sides).

The thoracic cardiac nerve originating from the thoracic ganglia the thoracic sympathetic trunk under the inferior cervical or the cervicothoracic ganglia was observed on 21/36 sides (53.8%; seven right, 14 left sides).

The superior, middle, and inferior cardiac nerves usually followed the common carotid, subclavian, and brachiocephalic arteries, whereas the thoracic cardiac nerve and some of the inferior cardiac nerves descended obliquely along the thoracic vertebrae or the intercostal vessels, as shown in Figs. 1, 2, and 3. The right thoracic cardiac nerve, in particular, followed complicated courses. Two descending courses for the right thoracic cardiac nerve were observed. The first course descended obliquely along the intercostal vessels and entered into the right venous porta via the azygos arch (drainage portion of the azygos vein to the superior vena cava), as shown in Figs. 2 and 4b. The other course was more complex, descending obliquely along the intercostal vessels, arriving at the thoracic aorta around the 6th to 8th thoracic vertebrae, turning there, ascending along the aorta, and connecting to the cardiac plexus along the arterial nutritional branch of the right intercostal artery, as shown in Figs. 3 and 4a. Moreover, none of the right thoracic cardiac nerves ascended obliquely to the vertebrae, regardless of the intercostal vessels.

Fig. 2
figure 2

Diagram of the origin, course, and distribution of the autonomic cardiac nerves viewed from a ventral aspect (no. 4). This case lacked a vertebral ganglion on the right side. The right thoracic cardiac nerve originating from the 2nd to 3rd thoracic ganglia and the inferior cardiac nerve originating from the lower portion of the cervicothoracic ganglion followed the intercostal vessels and the azyros vein entering from the right venous porta and innervating the heart at the areas shown by the black stars. The descending thoracic cardiac nerve is one of the right thoracic cardiac nerves that courses via the azygos vein and right venous porta. The arrowheads show the left thoracic cardiac nerve. The sympathetic cardiac nerves, vagal cardiac branches, and the mixture nerves (cardiac plexus) are colored in orange, green, and purple, respectively. [AI anterior interventricular branch, Ao aorta, Az azygos vein, CB circumflex branch, CC common carotid artery, CT cervicothoracic (stellate) ganglion, GV great cardiac vein, IB inferior (vagal) cardiac branch, IG inferior cervical ganglion, IN inferior cervical cardiac nerve, L lung, LA left atrium, LCA left coronary artery, MG middle cervical ganglion, MN middle cardiac nerve, P pectoral nerve, Ph phrenic nerve, PT pulmonary trunk, RA right atrium, RCA right coronary artery, RL recurrent laryngeal nerve of vagus nerve, SB superior (vagal) cardiac branch, Sbc nerve to subclavian muscle, SG superior cervical ganglion, SN superior cardiac nerve, SS suprascapular nerve, SVC superior vena cava, TB thoracic (vagal) cardiac branch, TG thoracic ganglia, TN thoracic cardiac nerve, VG vertebral ganglion, VN vertebral nerve, X vagus nerve, XI accessory nerve, XII hypoglossal nerve]

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Fig. 3
figure 3

Diagram of the origin, course, and distribution of the autonomic cardiac nerves viewed from a ventral aspect (no. 7). The superior cervical, middle cervical, vertebral, and cervicothoracic ganglia are present on both sides. The position of the cardiac plexus differs in each. The position of the cardiac plexus is close to the brachiocephalic trunk on the right side and close to the aortic arch on the left side. In this case, the other descending right thoracic cardiac nerve, shown by the arrowheads, followed the aorta. The thoracic cardiac nerve arose from the 2nd to 5th thoracic ganglia and descended along the intercostal vessels, reaching the thoracic aorta at the level of the 6th thoracic vertebra. After reaching the aorta, it turned upwards and ascended the aorta. Finally, the thoracic cardiac nerve connected to the cardiac plexus along the right intercostal artery. Interestingly, a sinuatrial branch (black star) originating from the right cardiac plexus surrounding the brachiocephalic trunk and left pulmonary branches (asterisks) originating from the right thoracic vagus nerve were observed. [AI anterior interventricular branch, Ao aorta, Az azygos vein, CB circumflex branch, CC common carotid artery, CT cervicothoracic (stellate) ganglion, GV great cardiac vein, IB inferior (vagal) cardiac branch, IG inferior cervical ganglion, IN inferior cervical cardiac nerve, L lung, LA left atrium, LCA left coronary artery, MG middle cervical ganglion, MN middle cardiac nerve, P pectoral nerve, Ph phrenic nerve, PT pulmonary trunk, RA right atrium, RCA right coronary artery, RL recurrent laryngeal nerve of vagus nerve, SB superior (vagal) cardiac branch, Sbc nerve to subclavian muscle, SG superior cervical ganglion, SN superior cardiac nerve, SS suprascapular nerve, SVC superior vena cava, TB thoracic (vagal) cardiac branch, TG thoracic ganglia, TN thoracic cardiac nerve, VG vertebral ganglion, VN vertebral nerve, X vagus nerve, XI accessory nerve, XII hypoglossal nerve]

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Fig. 4
figure 4

Descending recurrent right thoracic cardiac nerves following a course different from the described route. Only the descending thoracic cardiac nerve was observed. a Case 1 (no. 1). The thoracic cardiac nerve arose from the 3rd thoracic ganglia, descended along the intercostal artery, and connected to the cardiac plexus along the nutritional arterial supply to the cardiac plexus arising from the right intercostal artery, shown by the arrowheads. The arrows show a similar recurrent nerve originating from the 4th to 5th thoracic ganglia. b Case 2. The thoracic cardiac nerve arose from the 2nd to 4th thoracic ganglia and finally connected to the cardiac plexus. Both cases ascended along the intercostal vessels, arrived at the lower level of the thoracic aorta, turned, ascended from the aorta, and connected to the cardiac plexus, shown by the arrowheads. The arrows show a similar recurrent nerve originating from the 4th thoracic ganglion. [AI anterior interventricular branch, Ao aorta, Az azygos vein, CB circumflex branch, CC common carotid artery, CT cervicothoracic (stellate) ganglion, GV great cardiac vein, IB inferior (vagal) cardiac branch, IG inferior cervical ganglion, IN inferior cervical cardiac nerve, L lung, LA left atrium, LCA left coronary artery, MG middle cervical ganglion, MN middle cardiac nerve, P pectoral nerve, Ph phrenic nerve, PT pulmonary trunk, RA right atrium, RCA right coronary artery, RL recurrent laryngeal nerve of vagus nerve, SB superior (vagal) cardiac branch, Sbc nerve to subclavian muscle, SG superior cervical ganglion, SN superior cardiac nerve, SS suprascapular nerve, SVC superior vena cava, TB thoracic (vagal) cardiac branch, TG thoracic ganglia, TN thoracic cardiac nerve, VG vertebral ganglion, VN vertebral nerve, X vagus nerve, XI accessory nerve, XII hypoglossal nerve]

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The left thoracic cardiac nerve descended obliquely along the left intercostal vessels, arriving at the aortic arch. Thereafter, the left thoracic cardiac nerve connected to the cardiac plexus or entered from the left venous porta through the ventral/dorsal aspect of the aorta.

Parasympathetic cardiac branches arising from vagus nerve

The vagal cardiac branches were regarded as nerves with direct connections or connections via the cardiac plexus, excluding branches of the lung or surrounding vessels and organs. Each cardiac branch was named according to the origin of the vagus nerve from a developmental viewpoint, as follows: superior cardiac branch, which arose from the vagus nerve at the level of the upper (proximal) portion of the recurrent laryngeal nerve; inferior cardiac branch, which arose from the recurrent laryngeal nerve; and thoracic cardiac branch, which arose from the vagus nerve at the level of the lower (distal) portion of the recurrent laryngeal nerve.

The superior cardiac branch was observed on all sides (100%; 18 right sides, 18 left sides), with one to five branches observed in each individual (average, 2.2 branches; 1.9 right branches, 2.5 left branches).

The inferior cardiac branch was also observed on all sides (100%; 18 right sides, 18 left sides), with one to four branches (average, 2.1 branches; 2.4 right branches, 1.9 left branches).

The thoracic cardiac branch was observed on 28/36 sides (77.8%; right 18 sides; left 10 sides), with one to five branches (average, 2.0 branches; 2.6 right branches, 1.4 left branches).

Anatomical relationship among cardiac nerves (sympathetic), branches (vagus), and the cardiac plexus

The cardiac plexus was composed of the complex bifurcations and anastomoses of the cardiac nerves and branches as shown in Figs. 3, 4a, and 4b. The positions of the mixed nerves (cardiac plexus) between the sympathetic cardiac nerves and vagal cardiac branches were examined and are shown in Table 1. On the right side, the highest observed position of the mixture nerve was at the level of the cervical part of the common carotid artery (right side of Fig.2), whereas the general position was at the brachiocephalic trunk (right side of Fig. 3). On the left side, the highest observed position of the mixture nerve was at the level of the cervical part of the common carotid artery (left side of Fig.3), whereas the general position was at the aortic arch (left side of Figs. 2 and 4a). Consequently, most of the mixture nerves between the sympathetic cardiac nerve and the vagal cardiac branch were consistent, although the highest position of the mixture nerve varied from one individual to another. The right cardiac plexus usually surrounded the brachiocephalic trunk, whereas the left cardiac plexus surrounded the aortic arch. Furthermore, the cardiac plexus surrounding the great vessels on both sides was made from a larger cardiac plexus between the aortic arch and the pulmonary arterial trunk through the ventral/dorsal aspect of the aortic arch.

Table 1 Composition of cardiac plexus
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On the right side, several nerves were observed passing through the dorsal, rather than the ventral, aspect of the aortic arch. On the left side, no differences between the ventral and dorsal courses to the aortic arch were observed.

In addition, the cranial cardiac nerves and branches tended to be distributed from a medial position and the caudal cardiac nerves and branches from a lateral position.

Intrapericardium peripheral autonomic nerve distribution to the heart

After examining the origin and course of the autonomic nerves overall, the autonomic nerves innervating the heart were examined in detail using whole-mount preparations stained with Sudan black solution. However, the sympathetic and parasympathetic nervous systems innervating the heart could not be distinguished at the macroscopic level because of the cardiac plexus at the inlet/outlet level of the great vessels of the heart.

These mixtures of parasympathetic/sympathetic nerves branched or originated from the great cardiac plexus between the aortic arch and the pulmonary arterial trunk, coursed along the medial aspect of the aortic arch between the aortic arch and the pulmonary arterial trunk, and reached the coronary arteries (Fig. 5). Along the way, a number of branches from these mixture nerves were distributed directly to the atrium and the surrounding vessels and organs. The mixture nerves reaching the coronary arteries then descended, attached to the coronary arteries, and branched to the atria and ventricles.

Fig. 5
figure 5

Photographs showing the peripheral cardiac autonomic nerve distribution in the pericardium. a1 Right side. a2 Regional enlargement of a1. b1 Left side. b2 Regional enlargement of b1. The bundle (asterisk) of the cardiac plexus coursed between the aorta and the pulmonary trunk, ran along the great vessels and both coronary arteries, and was distributed to the atria, ventricles, and coronary arteries. [aI, anterior interventricular branch of left coronary artery, CB circumflex branch of left coronary artery, GV great cardiac vein, LA left atrium, LCA left coronary artery, PV, pulmonary vein, RA right atrium, RCA right coronary artery, AI Anterior interventricular branch, Ao aorta, Az azygos vein, CB circumflex branch, CC common carotid artery, CT cervicothoracic (stellate) ganglion, GV great cardiac vein, IB inferior (vagal) cardiac branch, IG inferior cervical ganglion, IN inferior cervical cardiac nerve, L lung, LA left atrium, LCA left coronary artery, MG middle cervical ganglion, MN middle cardiac nerve, P pectoral nerve, Ph phrenic nerve, PT pulmonary trunk, RA right atrium, RCA right coronary artery, RL recurrent laryngeal nerve of vagus nerve, SB superior (vagal) cardiac branch, Sbc nerve to subclavian muscle, SG superior cervical ganglion, SN superior cardiac nerve, SS suprascapular nerve, SVC superior vena cava, TB thoracic (vagal) cardiac branch, TG thoracic ganglia, TN thoracic cardiac nerve, VG vertebral ganglion, VN vertebral nerve, X vagus nerve, XI accessory nerve, XII hypoglossal nerve]

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Fig. 6
figure 6

Schematic representation of a general model of autonomic cardiac nerves. The sympathetic, parasympathetic (vagus), and mixture nerves (cardiac plexus) are represented in white, black, and gray, respectively. The superior cardiac, the middle cardiac, and the inferior cardiac nerves were easily distributed to the heart by following the great vessels. On the other hand, the course of the thoracic cardiac nerves was complex because of the long distance that had to be coursed to arrive at the heart. In particular, the right thoracic cardiac nerve followed a descending course that differed from previous descriptions. One nerve descended along the intercostal vessels and distributed to the heart via the azygos vein and right venous porta. The other arrived at the thoracic aorta at the levels of the 7th to 8th thoracic vertebrae after descending along the intercostal vessels. At that point it turned, ascended to the aorta, and connected to the cardiac plexus or was distributed to the heart via the left venous porta. The cranial cardiac nerves and branches tended to be distributed from the medial and caudal cardiac nerves and branches from lateral. The mixing positions (cardiac plexus) of the sympathetic cardiac nerve and the vagal cardiac branch, as well as the definitive morphology of brachial arteries with the recurrent laryngeal nerves, tended to differ on each side. [AI anterior interventricular branch, Ao aorta, Az azygos vein, CB circumflex branch, CC common carotid artery, CT cervicothoracic (stellate) ganglion, GV great cardiac vein, IB inferior (vagal) cardiac branch, IG inferior cervical ganglion, IN inferior cervical cardiac nerve, L lung, LA left atrium, LCA left coronary artery, MG middle cervical ganglion, MN middle cardiac nerve, P pectoral nerve, Ph phrenic nerve, PT pulmonary trunk, RA right atrium, RCA right coronary artery, RL recurrent laryngeal nerve of vagus nerve, SB superior (vagal) cardiac branch, Sbc nerve to subclavian muscle, SG superior cervical ganglion, SN superior cardiac nerve, SS suprascapular nerve, SVC superior vena cava, TB thoracic (vagal) cardiac branch, TG thoracic ganglia, TN thoracic cardiac nerve, VG vertebral ganglion, VN vertebral nerve, X vagus nerve, XI accessory nerve, XII hypoglossal nerve]

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Discussion

Sympathetic ganglia

Many anatomical studies on the communicating branches between the sympathetic ganglia and the spinal nerves have been published (Axford 1927–1928; Becker and Grunt 1957; Harman 1900; Hoffman 1957; Jamieson et al. 1952; Kuntz 1946; Mitchell 1953; Pick and Sheehan 1946; White and Smithwick 1952; Wrete 1959). These descriptions have been consistent and almost agree with the results here. The superior cervical and the cervicothoracic ganglia communicated with C1–3 and C7–8-T1–2, respectively. In humans, the cervicothoracic ganglia is always composed of the inferior cervical and only the 1st thoracic ganglia. On the other hand, the middle cervical and the vertebral ganglia are not constant with regard to size, position, and communicating branches with the spinal nerves. In other words, the superior cervical and the cervicothoracic ganglia are consistent, whereas the middle cervical and the vertebral ganglia are variable. Hoffmann (1957) and Pick (1970) mentioned that the latter two ganglia were generally small and that their ganglion cells could usually be found throughout the sympathetic trunk between the superior and the inferior cervical ganglia, even if they could not be readily observed. Verberne et al. (1999) clarified many things about the sympathetic cervical ganglia development using chick embryos. However, these results could not be applied to humans because there are many morphological differences between the species (Broek 1908).

To obtain a detailed understanding of the general morphology of the autonomic nervous system innervating the heart, comparative anatomical investigations are needed. In previous reports, the autonomic nervous distribution to the heart was examined in Japanese monkeys, Macaca fuscata (Kawashima and Sato 2000; Kawashima et al. 2001). In these studies, the cervicothoracic ganglion was usually composed of the inferior cervical, the 1st thoracic, and the 2nd thoracic ganglia (16/20 sides, 80.0%), but rarely only of the 1st thoracic ganglion (1/20 sides, 5.0%) and sometimes the 1st to 3rd thoracic ganglia (3/20 sides, 15.0%), in addition to the inferior cervical ganglion in the Japanese monkey, M. fuscata. On the other hand, the human cervicothoracic ganglion almost always consisted of the inferior cervical and only the 1st thoracic ganglia (30/36 sides, 83.3%). A single inferior cervical ganglion without the thoracic ganglion fusion was also observed in five sides (13.9%) in humans. Additionally, the positions of the cervicothoracic and the middle cervical ganglia in the Japanese monkey, M. fuscata, were compared with those in humans. In humans, the positions of these ganglia were higher (cranial) than those in Japanese monkeys. Therefore, comparative anatomical differences are likely related to evolution, and further comparative anatomical examinations using various primates will be required in the future.

From which did the vertebral ganglion derive—the inferior or the middle cervical ganglion?

Several authors have discussed the position and origin of the vertebral ganglion. Some authors have insisted that the vertebral ganglion should be regarded as being independent from other cervical ganglia because the characteristics of the vertebral ganglion are relatively consistent and appear at a higher frequency than those of the middle cervical ganglion (Mitchell 1953; Becker and Grunt 1957).

Whether the vertebral ganglion should be classified with other cervical ganglia or as accessory ganglia has been a subject of debate. One argument states that the vertebral ganglion belonged to or originated from the middle cervical ganglion (Axford 1927–1928; Woollard and Norrish 1933; Wrete 1959), while the other argument states that the vertebral ganglion belonged to or originated from the inferior cervical ganglion (Lazorthes and Cassan 1939; Guerrier 1944).

To shed light on this question, the morphology of the vertebral nerve was examined. Some vertebral nerves were found on one side; these vertebral nerves were derived from the cervicothoracic ganglion on 34/36 sides (94.4%), the vertebral ganglion on 26/34 (76.5) sides in which a vertebral ganglion was present, and the fusion ganglion between the middle cervical and the vertebral ganglia on 1/33 sides (3%). Therefore, the vertebral ganglion might originally derive from the inferior cervical or the upper part of the cervicothoracic ganglia, with part of a secondary component differentiating into the vertebral ganglion. The vertebral ganglion was regarded as being close to the cervicothoracic ganglion, and it did not usually communicate with the spinal nerves.

Developmental studies also seem to support the above hypothesis (Fernoholm 1971; Gomez 1958; His 1897; Kuntz 1946; Mitchell 1953; Pick 1970; Sharner 1930; Verberne et al. 1999). According to these earlier studies, the sympathetic trunk was initially generated in the thoracolumbar region. Next, the cervical and sacral regions of the sympathetic trunk were generated from the thoracolumbar sympathetic trunk. In view of the relationship between the present results and developmental findings, it is highly possible that the vertebral ganglion differentiates from the inferior cervical or the upper part of the cervicothoracic ganglia rather than the middle cervical ganglion. To clarify the complete differentiation of the vertebral ganglion, it would be necessary to use high primates or human embryos for investigation because no animal except adult primates has the vertebral ganglion.

Sympathetic cardiac nerves

Although many studies on cardiac nerves have been published (Ellison and Williams 1962; Fukuyama 1982; Hausmann 1956; Janes et al. 1986; Kuntz and Morehouse 1930; Mizeres 1963; Mitchell 1953; Pick 1970), their descriptions have varied regarding the origins of the nerves.

The opinion that the middle cardiac nerve originates mainly from the middle cervical and the vertebral ganglia is consistent with the present results (Mitchell 1953; Ellison and Williams 1962 Fukuyama 1982). However, the limits of cardiac nerve origin, namely the upper limit of the superior cardiac nerve and the lower limit of the thoracic cardiac nerve, differ among authors.

In phylogeny, the superior cardiac nerve is present only in humans (Broek 1908; Perman 1924; Schumacher 1902). Although the origin of the superior cardiac nerve from the superior cervical ganglion has been described as a defect in humans, a few authors have insisted that this situation exists (Ellison 1962, 83.3% on both sides; Fukuyama 1982, 93.8% on right, 100% on left). It is very difficult to trace the peripheral distribution of the superior cardiac nerve in addition to the courses that run behind the common carotid artery covered by the carotid sheath. Whether these cardiac nerves really reached the heart remained uncertain. In the present detailed analysis performed under a binocular stereomicroscope, however, the superior cardiac nerve was observed at a high frequency (88.9%), and its entire course from origin to peripheral distribution was successfully traced.

Although most authors have described a difference in the superior cardiac nerve between the left and right sides, the present observations showed no differences in frequency. However, right three sides did not have the superior cardiac nerve originating from the superior cervical ganglion or the cervical sympathetic trunk between the superior and the middle cervical ganglia. Therefore, although an apparent difference between the right and left sides was not observed, the frequency of the right superior cardiac nerve might be slightly less than the left.

The lower limit of the human thoracic cardiac nerve has also been discussed by many authors (Braeucker 1927). The lower limit of the thoracic cardiac nerve has been reported to be the 1st thoracic ganglion (Cruveilhier 1852; Hirschfeld 1866; Sappy 1889; Shinozaki 1929–1930), the 1st to 2nd thoracic ganglia (Müller 1924), the upper thoracic ganglia (Valentin 1843; Meckel 1817; Swan 1834; Bourgery 1844), the 4th thoracic ganglion (Mitchell 1953; Mizeres 1963), the 5th thoracic ganglion (Ellison 1962; Kuntz and Morehouse 1930), and the 7th thoracic ganglion (Saccomanno 1943). According to Fukuyama (1982), the limit is different between the right and left sides: the 5th and the 4th thoracic ganglia, respectively. The course of the lower thoracic cardiac nerve has been represented as running transversely through the thoracic vertebra, regardless of the course of the intercostal vessels, by Kuntz and Morehouse (1930). Moreover, Mitchell (1953) and Saccomanno (1943) represented the lower origin (5th to 7th thoracic ganglia) of the thoracic ganglia as ascending across the intercostal vessels to reach the heart at a position higher than the origin of the thoracic cardiac nerve. However, neither the ascending thoracic cardiac nerves nor the transversal thoracic cardiac nerves were observed in the present study.

A different course for the thoracic cardiac nerve has been reported in the Japanese monkey, M. fuscata (Kawashima et al. 2001). The thoracic cardiac nerve arose from the right 4th and 5th thoracic ganglia and descended obliquely along the intercostal vessels. After arriving at the thoracic aorta at the level of the 7th or 8th thoracic vertebra, the thoracic cardiac nerve turned and ascended along the aorta, finally entering from the left venous porta and innervating the left atrium and ventricle. The reason for this complex course was uncertain, but the existence of this complex course might be important and may be a potential course for the innervation of the human heart because a similar complex course was observed in 4/18 human right sides. The thoracic cardiac nerve might act as a right recurrent thoracic cardiac nerve in humans.

The superior, middle, and inferior cardiac nerves innervated the heart by following a simple course along the brachiocephalic trunk, common carotid, and subclavian arteries. On the other hand, the thoracic cardiac nerve, situated in the posterior mediastinum, had to follow a complex course because of the long distance to the heart in the middle mediastinum.

Additionally, a left thoracic cardiac nerve was observed on 14/18 sides (77.8%), whereas a right thoracic cardiac nerve was observed only on 7/18 sides (38.9%). The left thoracic cardiac nerve may have easily reached the heart because of the presence of the left aortic arch. However, the right thoracic cardiac nerve had to follow a complex course, requiring a longer distance to reach the heart because of the disappearance of the corresponding structure on the right side. Therefore, the roundabout course of the right thoracic cardiac nerve should be recognized as a collateral route for cardiac nerves.

Parasympathetic cardiac branches

Various names for the vagal cardiac branches have been proposed. Perman (1924) defined the cardiac branches arising from the vagus nerve cranial to the thoracic outlet as “Rr. cardiaci superiores” and those caudal to the thoracic outlet as “Rr. cardiaci inferiores.”

Mitchell (1953) divided the vagal cardiac branches into three groups: superior, middle, and inferior, arising from the vagus nerve in the upper half of the neck, the lower half of the neck, and the thorax, respectively.

Mizeres (1963) defined the cardiac branches arising from the vagus nerve until the lower border of the 6th cervical vertebra as the cervical cardiac branches, the cardiac branches from the vagus nerve between the 7th cervical and 1st thoracic vertebra as the cervicothoracic cardiac branches, and the cardiac branches from the vagus nerve caudal to the lower border of the 1st thoracic vertebra as the thoracic cardiac branches. These definitions were used for branches on both the right and left sides.

Tanaka et al. (1998) categorized the cardiac branches into arterial porta-related and venous-related groups based on their destination. Although they distinguished between right and left branches and paid attention to the developmental viewpoint, their definitions of the cardiac branches were too complex to be used practically.

Hausmann’s (1956) definitions may be the best and simplest way of describing differences between the right and left sides.

Several meaningful differences exist between the right and left thoracic cardiac branches. If branches to the lung are included in the term “cardiopulmonary branch,” the number of branches should be almost symmetrical. If this term is limited to the branches leading to the heart, however, the left and right sides will differ because the branching range of the left thoracic cardiac branch is very short compared with the right one.

Peripheral autonomic nervous distribution to the heart

The present observations clarified the main autonomic nerves descending into the arterial porta: superior cardiac nerve, middle cardiac nerve, inferior cardiac nerve, superior cardiac branch, and inferior cardiac branch. Cardiac nerves/branches were mainly observed running between the aortic arch and the pulmonary arterial trunk and innervating the heart along the coronary arteries. Additionally, fine nerve fibers entering from the venous porta and transverse and oblique sinuses of the pericardium were also observed. These results agree with the histochemical studies of Woollard (1925–1926) and Souza et al. (1996). According to Souza et al. (1996), the rat cardiac ganglia are regularly found in certain locations, namely, cranial to the pulmonary veins (44% of total), cranial and to the left of the superior vena cava (10%), in the interatrial groove (21%), to the left of the left pulmonary vein (11%), caudal to the pulmonary veins (12%), and in the wall of the coronary sinus (1%); the cardiac ganglia are not found on the auricular appendages. Pauza et al. (2000) analyzed the human cardiac ganglia and their connections/subplexuses in detail using a histochemical method. According to their results, the topography of epicardiac subplexuses was consistent from heart to heart. These human epicardiac neural plexuses are more or less associated with protuberances and/or grooves of the heart wall: coronary, interatrial, interventricular, and, their discovery, epicardiac nerve routes. These results describing the location of the cardiac ganglia correspond with the present results regarding the cardiac nerve/plexus. Both macroscopic and molecular analyses will be useful and necessary for unifying and resolving a more complete morphology in the future.

Morphogenesis of autonomic cardiac nerve from viewpoint of macroscopic anatomy

Tanaka et al. (1998) described and defined the cardiac branches in the Suncus from a developmental viewpoint and indicated that only the vagal cardiac branches exhibited a symmetrical developmental structure.

The present report described the anatomical architecture of the sympathetic cardiac nerves in addition to the vagal cardiac branches. In particular, the mixing position of the sympathetic cardiac nerves and vagal cardiac branches was asymmetrical in adults, whereas their positions were symmetrical from the developmental viewpoint. Moreover, although both sides of the autonomic cardiac nerves ran through the ventral/dorsal aspect of the aortic arch, the right autonomic cardiac nerves tended to follow a ventral course. Hirakow (1987), Ogawa (1952), and Shinozaki (1929–1930) also described this feature and suggested a relationship with the shift in the left ventricle from a left-lateral to ventral position. In addition, a series of embryological researches by Verberne et al. (1998, 2000a, 2000b) revealed much about autonomic nerve differentiations from the neural crest using the chick embryo. In their papers, they showed a difference in distribution between the right- and left-sided cardiac neural crest cells at the arterial pole and ventral cardiac plexus, whereas the right and left cardiac neural crest cells mixed in the dorsal cardiac plexus.

During the morphogenesis of the autonomic nerves to the heart, the vagal cardiac branches initially extend to the heart along the branchial arches, followed by the disappearance of the branchial arches, arteries, and organs. Thereafter, the sympathetic cardiac nerves secondarily extend to the heart, forming the cardiac plexus when the morphogenesis of the branchial arteries is nearly complete (Sharner 1930; Gomez 1958; Kuratani et al. 1991; Roberts 1991). Interestingly, the mixing positions (cardiac plexus) of the sympathetic cardiac nerve and the vagal cardiac branch, as well as the definitive morphology of brachial arteries with the recurrent laryngeal nerves, tended to differ on the two sides.