The Terminal Pathwav of the Lymphatic Systhm of the Human Heart Mario Feola, M.D., Robert Merklin, M.D., Sung Cho, M.D., and Stanley K. Brockman, M.D.

ABSTRACT Anatomical dissections in 9 human cadavers revealed the terminal pathway of the lym- phatic system of the left ventricle to be constituted mainly by channels emptying into the right angulus venosus (junction of the internal jugular and subcla- vian veins) at the base of the right side of the neck. This observation has clinical implications because it has been shown that a sampling of cardiac lymph provides the best method for analyzing myocardial metabolic abnormalities and that drainage of cardiac lymph alleviates the myocardial changes produced by ischemic injury.

Results of experimental studies in dogs have suggested an important role for the cardiac lym- phatic system in a variety of conditions [5, 6 , 10-13,151. Cardiac lymph has been found to be more sensitive than blood in reflecting the tissue changes that occur during acute myocardial ischemia [4]. Lymph drainage may alleviate the severity of ischemic injury 151, presumably by reducing interstitial edema and removing prod- ucts of anaerobic metabolism, lysosomal en- zymes, and other potentially toxic humoral fac- tors. Because these experimental observations carry clinical implications, it appeared impor- tant to determine whether the lymphatic system of the human heart is accessible outside the chest without a major surgical procedure.

A review of the literature provided an abun- dance of information on the cardiac lymphatic system of various animal species, particularly that of the dog, but scanty information about the human heart. These studies have been confined, primarily to intracardiac lymphatic distribution and drainage. The question of the terminal route

From the Division of Cardiothoracic Surgery, the Depart- ment of Anatomy, and the Department of Pathology, Jeffer- son Medical College of Thomas Jefferson University, Philadelphia, PA. Accepted for publication Apr 1, 1977. Address reprint requests to Dr. Feola, Texas Tech University School of Medicine, 1400 Wallace Blvd, Amarillo, TX 79106.

of the cardiac lymph has been answered only in the sense that ”a great variability exists in the outflow paths” [lo, 171. Therefore human ca- davers were anatomically dissected, and the lymphatic system was studied from the level of the epicardial plexus to the veins in the neck.

Materials and Methods The frozen-thawed cadavers of 1 child and 8 adults were dissected. The anterior thoracic wall was removed. The thymic veins were ligated close to the left innominate vein, and the thymus was excised. To isolate the right from the left major venous systems, the left innominate vein was isolated and divided between ligatures in its midportion. The right and left angulus ven- osus, each formed by the junction of the internal jugular vein with the homolateral subclavian vein, were exposed. To facilitate dissection, the inferior thyroid vein on each side was divided between ligatures. The anterior portion of the pericardial sac was excised. The subepicardial lymphatic plexus was visualized by means of intramyocardial injection of 5 ml of T-1824 dye (Evans blue) mixed with an equal amount of hydrogen peroxide, using a 27-gauge lymphan- giography cannula attached to a Harvard pump. Injections were made over a period of 30 min- utes in the anterior, obtuse marginal, and poste- rior portions of the left ventricular wall. Progres- sion of the dye for visualizing the supracardiac pathways was aided by massaging the heart during the course of injection. After 30 minutes the heart was excised, leaving the posterior wall of the left atrium in situ. The mediastinal lymph nodes, stained blue, were dissected and the ef- ferent channels followed up to their terminal por- tion. The right lymphatic duct and the thoracic duct were visualized. and each dissected up to its entrance into the corresponding angulus ven- osus. Diagrams of the anatomical pathways were immediately made.

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Results The lymphatic channels that were visualized fol- lowing the intramyocardial injection of dye formed a subepicardial plexus that tended to cover the surface of the left ventricle within the area delineated by the atrioventricular sulcus and the anterior and posterior interventricular sulci. The collecting trunks originating from this plexus followed the course of the coronary arte- rial system. The anterior interventricular trunk followed the course of the left anterior descend- ing coronary artery, the obtuse marginal trunk coursed along the obtuse marginal branch of the circumflex artery, and the posterior interven- tricular trunk followed the course of the pos- terior descending artery. When the posterior descending artery originated from the right coronary artery (dominant right coronary dis- tribution), the posterior interventricular trunk emptied into the right coronary channel in 5 of 9 cadavers. When the posterior descending artery originated from the circumflex artery (dominant left coronary distribution), the poste- rior interventricular trunk emptied into the left coronary channel. The right and left coronary channels converged toward the root of the aorta, where they formed one main supracardiac chan- nel in 7 of 9 cadavers, whereas they remained separate in 2. This channel crossed behind the pulmonary artery, in front of the trachea, toward a cardiac lymph node located in the space be- tween the superior vena cava and the brachiocephalic artery. The efferent channels from this node followed a cephalad route, emp- tying into either the right lymphatic duct or di- rectly into the right angulus venosus. In all cases, cannulation of the right lymphatic duct recovered stained fluid. In addition to the right lymphatic duct, the thoracic duct was found to be stained with dye in only 1 of 9 cadavers. In this 1 instance, the posterior interventricular trunk emptied into the right coronary channel, which remained separate from the left and ran toward the left angulus venosus.

Two main anatomical patterns were iden- tified. In pattern 1 (7 of 9 cadavers), the right and left coronary channels joined to form one main supracardiac channel that ascended toward the right lymphatic duct, which entered the right angulus venosus. Two varieties were recog-

nized, depending on whether the posterior in- terventricular trunk emptied into the right or the left coronary channel (Fig 1).

In pattern 2 (2 of 9 cadavers) the right and left coronary channels remained separate. These two channels ascended toward the right lym- phatic duct in 1 instance (Fig 2A), whereas they crossed in the other, with the right emptying into the thoracic duct which terminated in the left angulus venosus (Fig 2B). Thus the right lymphatic duct was the main terminal pathway, although not the exclusive one, for the lympha- tic system of the left ventricle. The typical ap- pearance of this duct following injection of dye into the left ventricle is shown in Figure 3.

Comment The purposes of this study were to define more fully the anatomical pathways of the lymphatics of the human heart and to determine whether operative access to the cardiac lymphatic system could be gained in humans without entering the chest. The rationale was two-fold: (1) access to cardiac lymph might provide a new avenue of investigation in the study of a variety of condi- tions affecting the heart; and (2) lymph drainage in the presence of myocardial edema might re- duce myocardial injury.

Textbooks of human anatomy provide scanty information about the lymphatics of the heart and none about their terminal pathway. Yet the existence of a rich lymphatic plexus in the heart has been known for more than 300 years. In 1665 Rudbeck [19] observed and described cardiac lymphatics in the dog. Studies abounded during the following two centuries, when descriptive anatomy flourished. William Hunter [7] injected mercury into subepicardial lymphatics of dogs, and some of these original heart specimens are still preserved in the Hunterian Museum of the University of Glasgow [2]. In 1889 Ranvier [18] stated that ”the mammalian heart can be consid- ered as a lymph sponge, the same as the heart of the frog is a blood sponge.” In 1924 Aagard [l] presented a detailed study of the cardiac lym- phatic system in man. He described the sub- epicardial plexus and traced its drainage to the mediastinal lymph nodes. He made no mention, however, of the terminal pathway into the ve- nous system. In 1928 Kampmeier [9] injected

533 Feola et al: Terminal Pathway of Human Heart Lymphatics

A L I A -

B u

Fig 1 . (A) In the anatomical pattern seen in 3 of 9 cadavers, the posterior interventricular trunk (PVT) empties into the right coronary channel (RCC); the anterior interventricular trunk (AVT) joins the obtuse marginal trunk (OMT) to form the left coronary channel (LCC); the right and left coronary channels join into one main supracardiac channel (MSC), which drains into the cardiac lymph node (CLN) situated between the superior vena cava and the brachiocephalic artery. The efferents of this node converge into the right lymphatic duct (RLD), which empties into the right angulus uenosus formed by the junction of the right subclavian vein (Scl V) and the internal jugular vein (IJV). ( B ) In 4 of 9 cadavers, the posterior interventricular trunk emptied into the left coronary channel, which joins the right in a cephalad course toward the right lymphatic duct.

B u

Fig 2 . (A) In this anatomical pattern ( I of 9 cadavers), the posterior interventricular trunk empties into the right coronary channel, which remains separate from the left coronary channel. However, the main supracardiac channels run cephalad toward the right angulus venosus. ( B ) In 1 of 9 cadavers, the right and left coronary channels remained separate and the right emptied into the left thoracic duct. (Abbreviations same as in Fig 1 .)

534 The Annals of Thoracic Surgery Vol 24 No 6 December 1977

Fig 3 . Anatomical dissection of a frozen-thawed adult cadaver. The right lymphatic duct enters the right angulus venosus (junction of the internal jugular and left subclavian vein, arrows). A ligature retracts the superior vena cava to expose the cardiac lymph node, which is visible in the space between the superior vena cava and the aorta (single arrow, right).

human embryos and fetuses with vital dye. He found that the cardiac lymphatics derive from two plexuses. One, arising as a branch from the upper thoracic duct near the left jugular lymph sac, extends down into the groove between the pulmonary artery and the aorta and grows along the right coronary artery into the right ventricle. The other, which is more important, grows from the right jugular sac, forms the pretracheal plexus, and extends along the left coronary ar- tery into the left ventricle. If this is the embryol- ogy, it would be reasonable to expect the 2 pri- mary lymphatic extensions into the embryonic heart to remain as definitive efferent channels of the adult organ. With this arrangement, the lymph of the left ventricle would drain toward the right angulus venosus, while the lymph of the right ventricle would drain toward the left. In the present study, however, it was found that the right and left coronary lymphatic channels join together into one main supracardiac lym- phatic channel in the majority of cases (7 of 9

cadavers). Thus cannulation of a terminal lymph channel in the area of the right angulus venosus would drain lymph deriving from both the right and left ventricles in the majority of cases, only from the left in some, and never from the right ventricle alone.

Until recently, no one could define any special role of the cardiac lymphatic system. In 1954 Foldi and associates [61 reported that mechanical insufficiency produced by ligation of the effer- ent lymphatics in dogs would cause interstitial myocardial edema and, in some c,ases, dissemi- nated focal necrosis. Although this observation did not seem to bear any relevance to human disease states it did suggest that lymph flow is of great importance for the heart. Miller and col- leagues [15] and Kline and co-workers [ll] ob- served that ligation of the cardiac collecting lymph channels in dogs produced chronic changes resembling fibroelastosis. These changes were partially confirmed by Symbas and co-workers [21]. Dilatation of the cardiac lymphatics, suggestive of impaired lymph drainage, was found in 2 patients who died of this disease [13]. Thus a new theory on the pathogenesis of myocardial fibroelastcasis was proposed.

In other studies, Kline and associates [141 found that cardiac lymphatic obstruction aggra- vated myocardial necrosis following coronary artery ligation in dogs. Furthermore, intramyo- cardial injections of autologous blood in the presence of chronic impairment of lymph drain- age produced much larger scars than in corre- sponding control animals [121. These studies suggest that the lymphatic system plays an impor- tant role in reducing tissue damage and in facilitating reparative processes within the myocardium.

Miller and associates [161 found that dogs with impaired cardiac lymph drainage are more prone to develop acute endocarditis and myocarditis following intravenous injection of staphylococci than are dogs with normal lym- phatics. While this observation does not indi- cate impairment of lymph drainage in en- domyocarditis, it does suggest that lymph stasis interferes with the local defensive mechanisms in the heart.

Feola and associates [5] found that an interre-

535 Feola et al: Terminal Pathway of Human Heart Lymphatics

lationship can be established between acute myocardial ischemia and lymph production and drainage. Following ligation of the circumflex artery in dogs [4], an increase in lymph produc- tion occurred, with changes in composition characterized by increases in protein content, hydrogen and potassium ion concentration, lac- tate, and lysosomal enzymes. Another study 131 showed that the transit time of vital dye is pro- longed when injected into an area of acute is- chemia compared to normal areas, suggesting a state of insufficient lymph drainage. In prelimi- nary studies [5], external drainage of cardiac lymph was found to diminish the severity of ischemic changes produced by coronary liga- tion.

The experimental studies have suggested that the cardiac lymphatic system might play a role in the pathophysiology of a variety of conditions. This role has not, thus far, been investigated in the human, probably because the system has been considered inaccessible. The present study provides evidence, although limited, that lymph from the left ventricle tends to drain into the right angulus venosus. To establish the rele- vance of this observation, additional questions remain to be answered. How would the terminal lymphatic system be visualized in the living state? Would cannulation of one of these termi- nal vessels obtain cardiac lymph, undiluted by pulmonary and mediastinal lymph? Could myo- cardial edema be relieved by drainage of the terminal ducts?

To answer these questions, experiments were again conducted in dogs. Although this study will be reported separately, it is sufficient to say here that visualization of the entire lympha- tic system of the heart can be achieved by the endocardial route, using an intracavitary cathe- ter capable of injecting a small amount of vital dye into the myocardial wall. With the aid of magnification, one of the visualized lymph channels can be cannulated before the right lymphatic duct or one of the neck veins is en- tered. This lymph is a sensitive indicator of myocardial ischemic injury, as its creatine phosphokinase enzyme activity rises above the plasma level within one hour of ischemia. De- termination of myocardial water content by weight differential of wetldry tissue shows a

lesser degree of edema in the ischemic myocar- dium of animals subjected to external drainage of all dye-stained terminal lymphatics.

This study indicates that access to the lymph of the left ventricle and decompression of the cardiac lymphatic system could be obtained in humans by cannulation of the terminal lympha- tic channels at the base of the right side of the neck, in the area of junction of the internal jugu- lar and subclavian veins.

References 1. Aagard OG: Les Vaisseaux Lymphatiques du

Coeur chez 1’Homme et chez Quelques Mammi- feres. Copenhagen, Munksgaard, 1924

2. Blair DM: The lymphatics of the heart: a hunter- ian memorandum. Glasgow Med J 103:363, 1925

3. Feola M: Cardiac lymph studies in acute myocar- dial ischemia. Edited by A. Lefer. Physiologic Mechanisms in Myocardial Ischemia. Spectrum Publications, Jamaica, NY (in press)

4. Feola M, Glick G: Cardiac lymph flow and compo- sition in acute myocardial ischemia in dogs. Am J Physiol 229:44, 1975

5. Feola M, Glick G, Pick R: Interrelations between cardiac lymph and experimental infarction in dogs. Clin Res 21:418, 1973

6. Foldi M, Romhanyi G, Ruzniak I, et al: Uber die Insuffizienz der Lymphstromung in Herzen. Acta Med Acad Sci Hung 6:61, 1954

7. Hunter W: Medical Commentaries. Part I, Con- taining a Plain and Direct Answer to Professor Monro. London, 1762 (cited by Aagard [ll)

8. Johnson RA, Blake TM: Lymphatics of the heart. Circulation 33:137, 1966

9. Kampmeier OF: O n the lymph flow of the human heart, with reference to the development of the channels and the first appearance, distribution and physiology of their valves. Am Heart J 4:210, 1928

10. Kline IK: Lymphatic pathways in the heart. Arch Pathol 88:638, 1969

11. Kline IK, Miller AJ, Katz LN: Cardiac lymph flow impairment and myocardial fibrosis: effects of chronic obstruction in dogs. Arch Pathol76:424, 1963

12. Kline IK, Miller AJ, Pick R, et al: The histologic effects of the injection of autologous blood into the ventricular myocardium of dogs with chronic impairment of cardiac lymph flow. Arch Pathol 76:424, 1963

13. Kline IK, Miller AJ, Pick R, et al: The relationship between human endocardial fibroelastosis and obstruction of the cardiac lymphatics. Circulation 30:728, 1964

14. Kline IK, Miller AJ, Pick R, et al: The effects of chronic impairment of cardiac lymph flow on

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myocardial reactions after coronary artery liga- tion in dogs. Am Heart J 68:515, 1964

15. Miller AJ, Pick R, Katz LN: Ventricular en- domyocardial pathology produced by chronic cardiac lymphatic obstruction in the dog. Circ Res 8:941, 1960

16. Miller AJ, Pick R, Katz LN: Lymphatics of the mitral valve of the dog: demonstration and dis- cussion of the possible significance. Circ Res 9:1005, 1961

17. Polikarpov LS: Individual variability of lymph outflow paths from the human heart. Arkh Anat Gistol Embriol 62:48, 1972

18. Ranvier L: Traite Technique d’Histologie. Second edition. Paris, Savy, 1889

19. Rudbeck 0: Nova Exercitatio Anatomica, Exhi- bens Ductus Hepaticos Aquosuis et Vasa Glan- dularum Serosa, Nunc Primum Inventa, Aen- eisque Figuris Delineata. Arosiae, 1653 (cited by Aagard [l])

20. Ruszniak I, Foldi M, Szabo G: Lymphatics and Lymph Circulation: Physiology and Pathology. New York, Pergamon, 1960

21. Symbas PN, Cooper T, Gantner GA Jr, et al: Lym- phatic drainage of the heart: effects of experimen- tal interruption of lymphatics. Surg Forum 14:254, 1963

22. Yoffey JM, Courtice FC: Lymphatics, Lymph and the Lymphomyeloid Complex. New York, Academic, 1970

Notice from the Society of Thoracic Surgeons The Fourteenth Annual Meeting of The Society of Thoracic Surgeons will be held at the Sheraton Twin Towers Hotel in Orlando, FL, on Jan 23-25,1978. There will be a $100 registration fee for nonmember physicians except for guest speakers, authors, and coauthors on the pro- gram. Residents and fellows may register with- out fee by presenting a letter from their chief of service. Nurses and paramedical personnel may register upon payment of a $30 registration fee by presenting a letter from a member of the Society.

There will be a Postgraduate Program on Jan 22, 1978, preceding the annual meeting, for which the registration fee is $20 (including luncheon).

Because The Society of Thoracic Surgeons is an organization accredited for continuing medical education, each hour of the postgraduate course and scientific sessions meets the criteria for one hour credit in Category 1 of the Physicians Rec- ognition Award of the American Medical As- sociation.