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J Thorac Cardiovasc Surg 1997;113:453-461
© 1997 Mosby, Inc.

SURGERY FOR CONGENITAL HEART DISEASE

MORPHOLOGY OF THE PULMONARY AND AORTIC ROOTS WITH REGARD TO THE PULMONARY AUTOGRAFT PROCEDURE

Supported in part by a grant from the Netherlands Heart Foundation (NHS No. 89.237).

Received for publication July 2, 1996 revisions requested August 27, 1996; revisions received Sept. 26, 1996 accepted for publication Sept. 30, 1996. Address for reprints: Margot M. Bartelings, MD, PhD, Department of Anatomy and Embryology, Leiden University, P.O. Box 9602, 2300 RC Leiden, The Netherlands.

Abstract

Aortic root replacement with the pulmonary autograft warrants a thorough histologic comparison of the morphologic characteristics of the pulmonary and aortic roots. For this purpose nine normal heart specimens (7 neonatal and 2 adult hearts) were studied. Histologic study confirmed the collagenous anulus in both roots to be a complex circular-shaped structure, intricately interposed between the elastic lamellae of the arterial wall and the ventricular structures of the heart. In the sinus the elastic lamellae of the arterial wall continue along the luminal side with collagen being situated at the outside. At the interleaflet triangle this relation is reversed. Surprisingly, islets of elastic fibers were found in the otherwise completely collagenous interleaflet triangles. The amount of elastic lamella distal to the commissures was in both arteries higher than that in the middle of the sinuses, with a preponderance in the aorta as compared with the pulmonary trunk. The pulmonary root anulus proximally inserts into the relatively thin right ventricular myocardium, whereas the aortic root anulus inserts into the thick left ventricular myocardium and several fibrous structures. The pulmonary root is hardly supported by the right ventricular myocardium, whereas the aortic root is supported by its wedged position between the left and right atrioventricular anuli and the bulging thick left ventricular myocardium. When the pulmonary autograft is used for aortic root replacement it should be inserted as proximally as possible to get the support of the fibrous structures of the left ventricular outflow tract and the surrounding ventricular and atrial myocardium.

Morphologic descriptions of the aortic and pulmonary valve and root had already been published by the first half of this century. ^1,2 More recent studies describe the morphology of the aortic valve and root in relation to function ³ and in relation to congenital malformations. ^4,5 With the use of the pulmonary autograft for aortic root replacement, a method developed by Ross ⁶ in 1986, the question with regard to the suitability of the pulmonary valve and root for use in the aortic position is relevant. The clinical results of the pulmonary autograft implanted in the aorta with the subcoronary technique ⁷ are good. ⁸ However, when the complete aortic root is replaced by the pulmonary root, not only the pulmonary valves but also the pulmonary wall are exposed to systemic pressures. Although the short-term results with this technique are satisfactory with regard to the clinical performance, ^9-11 some surgeons advise wrapping the pulmonary autograft to avoid dilation. ^7,12 In this regard the pathophysiologic nature of native aortic regurgitation caused by aortic root dilation ^13,14 may also be applicable to the pulmonary autograft in the aortic position.

Therefore a microscopic morphologic study of the components of the pulmonary and aortic roots and their proximal insertions with a description of the surrounding structures seems appropriate and may give insight into the differences between the pulmonary and aortic roots in general and the consequences of implantation of the pulmonary autograft in the aortic position.

Material and methods

Material.
Nine normal heart specimens were studied. Seven hearts of children who died perinatally at a mean gestational age of 38 weeks (range 34 to 40 weeks) were obtained from the Leiden Collection of heart-lung specimens. Two adult hearts (42 and 47 years old) from the Department of Pathology of the University Hospital Rotterdam were included to investigate possible age-related differences.

Methods.
The specimens were cut in serial sections approximately perpendicular to the aortic axis with a thickness of 10 µm. Four consecutive sections of the entire specimen were put together on one slide. The slides were stained alternately with azan, resorcin-fuchsin, hematoxylin-eosin, and modified van Gieson's stains. Because the pulmonary axis is not parallel to the aortic axis, the plane of sectioning of the pulmonary trunk was not transverse. With use of these sections three-dimensional reconstructions were made to clarify and describe the relationships between the elastic and collagenous components of the pulmonary and aortic roots and of their insertions in the myocardium.

Elastic lamellae in the wall of the pulmonary trunk and aorta were counted in each specimen at six different places: in the middle of each of the three sinus walls and 2 mm distal to each of the commissures.

Terms were defined as follows.

Pulmonary root.
The pulmonary root was defined as the first part of the pulmonary trunk, from the insertion of the pulmonary anulus in the right ventricular myocardium, including the semilunar valve leaflets, the wall of the sinuses, the interleaflet triangles, the commissures, and the sinotubular junction.

Aortic root.
The aortic root is the first part of the aorta, from the insertion of the aortic anulus in the left ventricular myocardium and the continuation in proximal fibrous structures, including the semilunar valve leaflets, the wall of the sinuses of Valsalva (with the coronary orifices), the interleaflet triangles, the commissures, and the sinotubular junction.

Sinuses.
The sinuses include pockets or cavities of the pulmonary and aortic roots between the arterial wall and the arterial side of the semilunar valve leaflets. The sinuses of the aorta are named according to the coronary arteries with their ostia (left and right coronary sinus), and the sinus without a coronary ostium is the noncoronary sinus. The pulmonary sinuses are named by their relationship to the aortic sinuses: left facing, right facing, and nonfacing sinuses. ¹⁵

Sinotubular junction.
The sinotubluar junction was defined as the borderline between the more distal arterial wall and the thinner arterial wall of the sinuses.

Commissures.
The commissures are the sites at the arterial wall where two valve leaflets meet.

Interleaflet triangle.
The triangular part of the arterial wall in between two sinuses with its base on the ventricular myocardium and extending up to the commissures is the interleaflet triangle. ^4,5

Anulus.
The anulus is the fibrous structure in the arterial root to which the semilunar valve leaflets are attached.

Proximal fibrous structures.
Proximal fibrous structures are fibrous structures proximal to the aortic anulus.

Surrounding structures.
Peripheral structures that lie adjacent to the aortic or pulmonary root are surrounding structures.

Statistical analysis.
The mean values of the elastic lamella counts at both levels in the pulmonary trunk and aorta were calculated. A t test was used to evaluate the differences between both levels of pulmonary trunk and aorta and between both arteries at the same level.

Results

Pulmonary root.
The distal part of the pulmonary trunk consists largely of elastic lamellae arranged in a concentric fashion. Collagen and smooth muscle cells are visible between its layers. Going upstream the pulmonary wall shows three protrusions at the luminal side. Further toward the heart, collagenous condensations are found in the center of these protrusions, constituting the most distal extension of the commissures. Slightly more proximally, these collagenous condensations bulge into the arterial lumen, and here the valve leaflets originate (Fig. 1 and Fig. 2, A and B).

View larger version (108K): [in this window] [in a new window]   Fig. 1. Section of the distal part of the aortic root. 1, Protrusion of the elastic (darkly stained) vessel wall, slightly above a commissure; 2, collagenous (lightly stained) area surrounded by elastic lamellae, constituting the most distal extension of the commissure; 3, the commissure itself, where the two valve leaflets meet. AS, Atrial septum; RCA, right coronary artery.

View larger version (42K): [in this window] [in a new window]   Fig. 2. Schematic drawings of the arterial root after three-dimensional reconstruction showing longitudinal sections through (A) the middle of a sinus wall and (B) the middle of a commissure and interleaflet triangle.

View larger version (128K): [in this window] [in a new window]   Fig. 3. Section through the aortic root at a more proximal level than that in Fig. 1. The arrows indicate part of the borderline between the lightly stained collagen and the slightly darker stained myocardium. The elastic lamellae are darkly stained. 1, Noncoronary sinus with elastic lamellae makes up the entire thickness of the sinus wall; 2, slightly more proximally, the right coronary sinus shows elastic lamellae on the luminal side and collagenous tissue inserting into the myocardium on the outer side; 3, more proximally, at the base of the left coronary sinus, there is only collagenous tissue. The arrowheads indicate the elastic fibers at the luminal side of the interleaflet triangles. AS, Atrial septum.

View larger version (24K): [in this window] [in a new window]   Fig. 4. A, Schematic representation of the pulmonary root related to the site of insertion into the myocardium. RV, Right ventricle; RFS, right facing sinus; LFS, left facing sinus; NFS, nonfacing sinus. B, Schematic representation of the aortic root related to the site of insertion into the myocardium and fibrous structures. The left fibrous trigone is situated between the anterior mitral valve leaflet and the left ventricular free wall. LV, Left ventricle; RCS, right coronary sinus; LCS, left coronary sinus; NCS, noncoronary sinus; MS, membranous septum; RFT, right fibrous trigone; M, anterior mitral valve leaflet.

The pulmonary root has no surrounding structures except for the adjacent aorta. In some cases (n = 2) a collagenous connection was present between the aortic and pulmonary roots. This collagenous connection extended from the interleaflet triangle between the right and left pulmonary sinuses to the interleaflet triangle between the right and left coronary sinuses of the aortic root (Fig. 5). The right ventricular myocardium, the septal part more than the thin free wall, slightly bulges on the outside. Loose connective tissue is situated in between the pulmonary root and the myocardium.

View larger version (119K): [in this window] [in a new window]   Fig. 5. Section of the pulmonary and aortic roots. The arrow indicates the conus tendon between both roots. Ao, Aorta; PT, pulmonary trunk; RCA, right coronary artery.

View larger version (85K): [in this window] [in a new window]   Fig. 6. Detail showing part of the isolated condensation of elastic fibers (arrow) in the interleaflet triangle, reconstructed in Fig. 2.

View larger version (110K): [in this window] [in a new window]   Fig. 7. Section of the proximal part of the aortic root. The collagen is darkly stained. The arrow indicates the "third body," situated at the proximal part of the right coronary sinus. The asterisk indicates the membranous septum. RFT, Right fibrous trigone; RA, right atrium; M, anterior mitral valve leaflet; LV, left ventricle; T, tricuspid valve leaflet.

The aortic root has more surrounding structures than the pulmonary root. The thick left ventricular myocardium and septal myocardium bulge on the outside, forming a collar around the proximal part of the aortic root. Loose connective tissue is situated between the myocardium and the aortic root. The anuli of the right and left atrioventricular valves are continuous with the membranous septum and left fibrous trigone, respectively, and both are continuous with the dorsal side of the right fibrous trigone. The aorta apparently is in a wedged position between the right and left atrioventricular anuli. The right fibrous trigone is also connected to the atrial myocardium but fingerlike protrusions of collagen are not present. In three specimens the noncoronary sinus distal to the right fibrous trigone was closely related to atrial muscle fiber. In the others loose connective tissue was present between these structures.

Elastic lamella count.
The site 2 mm distal to the commissures appeared to be representative for the distal part of the pulmonary trunk and aorta. The numbers of elastic lamellae at this level and in the middle of the sinus walls are presented in Table II. The difference between pulmonary trunk and aorta at the distal level was evident: there were more elastic lamellae in the aortic wall compared with the pulmonary wall (66 versus 52; p < 0.0008). There was no statistically significant difference in the middle of the sinuses between the two arteries (40 and 39, respectively; p = 0.46). Thus the difference within the aorta at the two levels (p = 0.000004) was larger than the difference within the pulmonary trunk (p < 0.004). In the nine specimens studied, the two adult hearts exhibited more elastic lamellae at the distal level of the two arteries than the other specimens. In the middle of the aortic and pulmonary sinus walls there were no differences.

As recognized by several authors the components of the arterial roots comprise the vessel wall, characterized by concentric lamellae, ventricular structures (myocardial or collagenous), and a collagenous structure that is interposed between the vessel wall and the ventricular structures. ^1,2 It is this interposed collagenous structure, to which the valve leaflets are attached, that we consider to represent the anulus. Zimmerman ¹⁶ in 1969 described this structure as "a crownlike formation of collagenous tissue." By 1923, Lewis and Grant ¹ had observed that the anulus "is not a simple ring." Anderson and colleagues ⁵ in 1991 opposed the use of the term aortic anulus on the grounds that "the attachments of the leaflets are not arranged in a ringlike fashion." Indeed, the leaflets follow a semilunar pattern. It is, however, not the attachment of the leaflets that we consider to represent the anulus, but the entire collagenous structure to which they are attached. This collagenous structure is basically a circular band that has its distal edge formed like a three-peaked crown, whereas its proximal border is characterized by three fimbriated, less pronounced curves. Its connection to the adjacent vessel wall distally and the ventricular structures proximally is very intricate. Notwithstanding the fact that in the case of the aorta a distinctive borderline cannot be seen between part of the anulus and the proximal fibrous structures, we consider the term anulus applicable.

The reversed relation of the elastic vessel wall and the collagenous anulus in the sinus wall (elastic layer inside) and in the interleaflet triangle (elastic layer outside) as found by us in both the pulmonary and aortic root had already been recognized in the aortic root by Lewis and Grant. ¹ The isolated condensations of elastic fibers in the interleaflet triangles of the aortic (more pronounced) and the pulmonary (less conspicuous) roots have, as far as we are aware, not been described before. They might be indicative of elastic properties to pass on end-diastolic left ventricular pressure, which is useful in the opening mechanism of the semilunar valves, as described for the aortic valve by Thubrikar and associates. ¹⁷ A collagenous tendon between two opposing interleaflet triangles of the pulmonary and aortic roots was found in two of the nine specimens. This structure is known as the conus tendon. ^18,19 The prevalence of this tendon is not known. Kerr and Goss, ²⁰ having studied the relation between the pulmonary and aortic valves in 200 hearts, did not mention this tendon. The collagenous condensation at the proximal part of the right coronary sinus wall, as present in three of nine specimens, has been described before by Zimmerman, ^16,21 who assigned the term third body to it. He described it as being continuous with the anterior part of the membranous septum. This "third body" was, however, continuous with the membranous septum in only one of our specimens, whereas in the other two specimens the third body and the membranous septum were separated by muscular ventricular septum.

With respect to the differences between the pulmonary and aortic roots it appears that these are both major and minor. The anulus of the pulmonary root is anchored in myocardium over its entire circumference, whereas this applies to only half of the aortic circumference. The right ventricular myocardium is thin, thus providing a more delicate attachment of the pulmonary anulus. This contrasts with the thick left ventricular myocardium and the proximal continuation of more than half of the aortic anulus in fibrous structures such as the membranous septum, the right fibrous trigone, the anterior leaflet of the mitral valve, and the left fibrous trigone. The sinus walls and the interleaflet triangles of the aorta appear to be thicker. Surprisingly, we found no significant differences between the elastic lamella counts in the pulmonary and aortic sinuses, nor was there a significant difference at this level between the counts in children and adults. Although the number of studied specimens was small, it appears that the number of lamellae in the sinuses is fixed. The difference in thickness of the sinus walls might be the result of a difference in the amount of collagen, smooth muscle cells, or ground substance and/or in the thickness of the elastic lamellae themselves. At the level distal to the commissures, the number of elastic lamellae in both arteries was higher than that in the sinus walls. In contrast to the situation in the sinus walls, at the distal level, this number is not fixed. In agreement with the findings of others, ^22,23 the adult specimens showed a higher count. The aorta has more elastic lamellae than the pulmonary trunk and this difference was even more pronounced in the adult heart specimens. With regard to a possible growth potential of these lamellae no conclusions can be drawn, because the thickness of the lamellae, their organization, and other components of the medial layer of the vessel wall have to be taken into account. ^24,25

With regard to the surrounding structures the aorta is better encased. In addition to the thick left ventricular myocardium that bulges and forms a collar around the proximal part of the aortic root, the aortic root is wedged between the right and left atrioventricular anuli and atrial myocardium. The pulmonary root is only slightly supported by the thin right ventricular myocardium and the adjacent aorta.

When the pulmonary autograft is used for aortic root replacement the following aspects are relevant. It should be appreciated that the structures of the semilunar valve leaflets ² and the walls of the sinuses in both roots are not essentially different. The pulmonary autograft, however, has thinner interleaflet triangles, the proximal border consists of a ridge of relatively thin right ventricular myocardium, and it does not contain the proximal fibrous structures of the left ventricular outflow tract. For this reason the pulmonary autograft should be trimmed to leave only a few millimeters of right ventricular myocardium as suture area, followed by implantation at the level of the anulus ⁹ to obtain maximal support of the fibrous structures of the left ventricular outflow tract and the surrounding ventricular and atrial myocardium. In contrast, in an extended autograft procedure this support is not optimal because these fibrous structures are not left intact as a result of the procedure.

Acknowledgments

We thank the Department of Pathology of the University Hospital Rotterdam for permission to study two of their heart specimens.

Footnotes

From the Department of Cardiopulmonary Surgery^a of the University Hospital Dijkzigt, Rotterdam, and the Department of Anatomy and Embryology^b of Leiden University, Leiden, The Netherlands.

References

1. Lewis T, Grant RT. Observations relating to subacute infective endocarditis. Heart 1923;10:21-99.
   
2. Gross L, Kugel MA. Topographic anatomy and histology of the valves in the human heart. Am J Pathol 1931;7:445-73.
   
3. Brewer RJ, Deck DJ, Capati B, Nolan SP. The dynamic aortic root: its role in aortic valve function. J Thorac Cardiovasc Surg 1976;72:413-7.[Abstract]
   
4. Angelini A, Ho SY, Anderson RH, et al. The morphology of the normal aortic valve as compared with the aortic valve having two leaflets. J Thorac Cardiovasc Surg 1989;98:362-7.[Abstract]
   
5. Anderson RH, Devine WA, Ho SY, Smith A, McKay R. The myth of the aortic anulus: the anatomy of the subaortic outflow tract. Ann Thorac Surg 1991;52:640-6.[Abstract]
   
6. Ross DN. Aortic root replacement with a pulmonary autograft: current trends. J Heart Valve Dis 1994;3:358-60.[Medline]
   
7. Ross DN. Replacement of aortic and mitral valves with a pulmonary autograft. Lancet 1967;2:956-8.[Medline]
   
8. Matsuki O, Okita Y, Almeida RS, et al. Two decades' experience with aortic valve replacement with pulmonary autograft. J Thorac Cardiovasc Surg 1988;95:705-11.[Abstract]
   
9. Hokken RB, Bogers AJJC, Taams MA, et al. Aortic root replacement with a pulmonary autograft. Eur J Cardiothorac Surg 1995;9:378-83.[Abstract]
   
10. Kouchoukos NT, Davila-Roman VG, Spray TL, Morphy SF, Perillo JB. Replacement of the aortic root with a pulmonary autograft in children and young adults with aortic valve disease. N Engl J Med 1994;330:1-6.[Abstract/Free Full Text]
    
11. Elkins RC, Knott-Craig CJ, Ward KE, McCue C, Lane MM. Pulmonary autograft in children: realized growth potential. Ann Thorac Surg 1994;57:1387-94.[Abstract]
    
12. Pacifico AD, Kirklin JK, McGiffin DC, Matter GJ, Nanda NC, Diethelm AG. The Ross operation: early echocardiographic comparison of different operative techniques. J Heart Valve Dis 1994;3:365-70.[Medline]
    
13. Bellhouse BJ, Bellhouse F, Abbott JA, Talbot L. Mechanism of valvular incompetence in aortic sinus dilatation. Cardiovasc Res 1986;34:83-94.
    
14. Roman MJ, Devereux RB, Niles NW, et al. Aortic root dilatation as a cause of isolated, severe aortic regurgitation. Ann Intern Med 1987;106:800-7.
    
15. Kirklin JW. Anatomy, dimensions, and terminology. In: Kirklin JW, Barratt-Boyes B, eds. Cardiac surgery. New York: John Wiley, 1993:3-60.
    
16. Zimmerman J. The functional and surgical anatomy of the aortic valve. Isr J Med Sci 1969;5:862-6.[Medline]
    
17. Thubrikar M, Nolan SP, Bosher LP, Deck JD. The cyclic changes and structure of the base of the aortic valve. Am Heart J 1980;99:217-24.[Medline]
    
18. Patten BM. The development of the heart. In: Gould SE, ed. Pathology of the heart. Springfield, Illinois: Charles Thomas, 1960:24-92.
    
19. Tandler J. Anatomie des Herzens. Jena: Verlag von Gustav Fischer, 1913:140-51.
    
20. Kerr A, Goss CM. Retention of embryonic relationship of aortic and pulmonary valve cusps and a suggested nomenclature. Anat Rec 1956;125:777-82.[Medline]
    
21. Zimmerman J. The functional and surgical anatomy of the heart. Ann R Coll Surg Engl 1966;39:348-66.[Medline]
    
22. Plank L, James Y, Wagenvoort CA. Caliber and elastin content of the pulmonary trunk. Arch Pathol Lab Med 1980;104:238-41.[Medline]
    
23. Wolinsky H. Comparison of medial growth of the human thoracic and abdominal aortas. Cric Res 1970;27:531-8.[Abstract/Free Full Text]
    
24. Schlatmann TJM, Becker AE. Histologic changes in the normal aging aorta: implications for dissecting aortic aneurysms. Am J Cardiol 1977;39:13-20.[Medline]
    
25. Saldana M, Arias-Stefia J. Studies on the structure of the pulmonary trunk: 1—normal changes in the elastic configuration of the human pulmonary trunk at different ages. Circulation 1968;27:1086-93.
    

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