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Morphological basis for the study of the interatrial septum in the human fetus

Abstracts

OBJECTIVE: To describe morphological features of the interatrial septum in normal fetuses, especially foramen ovale (FO) and septum primum (SP), in order to compare septum primum excursion with foramen ovale diameter. METHODS: Septum primum excursion (SPE) toward the left atrium (LA) and foramen ovale diameter (FOD) were measured in the hearts of ten formaldehyde-fixed human fetuses ranging from 28 to 36 weeks of gestation. Histological sections were obtained from the foramen ovale (FO), septum primum (SP), septum secundum (SS), left atrium (LA), and right atrium (RA). RESULTS: FOD and SPE measurements were the following: FOD 3.1-3.5 mm and SPE 2.8-3.1 mm in three fetuses with presumed gestational age (GA) of 28 weeks; FOD 3.3-3.5 mm, and SP excursion 4.0-5.0 mm in four fetuses with presumed GA of 34 weeks, plus FOD 3.3-4.5 mm and SPE 6.0-9.0 in three fetuses with presumed GA of 36 weeks. Cardiac muscular fibers were identified in both the septum primum and secundum. CONCLUSION: Based on its muscular components, it may be suggested that SP is active in character, influencing blood flow through the FO, SP mobility, and its excursion into the LA.

Fetal heart; heart septum; heart septal defects, atrial


OBJETIVO: Descrever observações morfológicas sobre o septo interatrial em fetos normais, especialmente o forame oval e o septo primeiro, de forma a comparar a excursão do septo primeiro com o diâmetro do forame oval. MÉTODOS: As medidas da excursão do septo primeiro (ESP) em direção ao átrio esquerdo (AE) e do diâmetro do forame oval (DFO) foram realizadas em corações de dez fetos humanos formolizados com 28 a 36 semanas. Os cortes histológicos foram feitos no FO, SP, septo segundo e nos AE e AD. RESULTADOS: Os resultados da análise anatômica estão expressos em amplitude das medidas do DFO e da ESP: 3 fetos com idade gestacional (IG) presumida de 28 semanas, DFO (3,1-3,5 mm) e ESP (2,8-3,1 mm); 4 fetos com IG presumida de 34 semanas, DFO (3,3-3,5 mm) e ESP (4,0-5,0 mm); e 3 fetos com IG presumida de 36 semanas, DFO (3,3-4,5 mm) e ESP (6,0-9,0). Foram identificadas fibras musculares cardíacas no SP e no segundo. CONCLUSÃO: Pode-se sugerir que o SP apresenta caráter ativo devido às fibras musculares que o constituem, influenciando o fluxo sangüíneo através do FO, a mobilidade do SP e a sua excursão para o interior do AE.

Coração fetal; septo cardíaco; defeitos do septo atrial


ORIGINAL ARTICLE

Morphological basis for the study of the interatrial septum in the human fetus

Hugo Becker Amaral; Paulo Zielinsky; Aron Ferreira da Silveira; Ijoni Costabeber; Luiz Henrique Nicoloso; Olmiro Cezimbra de Souza Filho; Marcelo Salum; João Luiz Manica; Juliana Silveira Zanettini; Ane Micheli Costabeber

Fetal Cardiology Unit of the Cardiology Institute of Rio Grande do Sul, and the Morphology Department of the Health Sciences Center of the Federal University of Santa Maria – Porto Alegre, RS, Brazil

Mailing address Mailing address: Luiz Henrique Nicoloso Av. Princesa Isabel, 370 90620-001 – Porto Alegre, RS - Brazil E-mail: zielinsky.pesquisa@cardiologia.org.br

SUMMARY

OBJECTIVE: To describe morphological features of the interatrial septum in normal fetuses, especially foramen ovale (FO) and septum primum (SP), in order to compare septum primum excursion with foramen ovale diameter.

METHODS: Septum primum excursion (SPE) toward the left atrium (LA) and foramen ovale diameter (FOD) were measured in the hearts of ten formaldehyde-fixed human fetuses ranging from 28 to 36 weeks of gestation. Histological sections were obtained from the foramen ovale (FO), septum primum (SP), septum secundum (SS), left atrium (LA), and right atrium (RA).

RESULTS: FOD and SPE measurements were the following: FOD 3.1-3.5 mm and SPE 2.8-3.1 mm in three fetuses with presumed gestational age (GA) of 28 weeks; FOD 3.3-3.5 mm, and SP excursion 4.0-5.0 mm in four fetuses with presumed GA of 34 weeks, plus FOD 3.3-4.5 mm and SPE 6.0-9.0 in three fetuses with presumed GA of 36 weeks. Cardiac muscular fibers were identified in both the septum primum and secundum.

CONCLUSION: Based on its muscular components, it may be suggested that SP is active in character, influencing blood flow through the FO, SP mobility, and its excursion into the LA.

Key words: Fetal heart, heart septum/anatomy & histology, heart septal defects, atrial.

Introduction

Embryonic development of the human heart depends on cell-cell interaction, particularly myocardial and mesenchymal cells1-6. This interaction accounts for the differentiation and morphogenesis of specific areas in the heart, among them cardiac septa7-10. The endocardial cushion, a clustering of endocardial and mesenchymal cells, plays a direct role in cardiac septa and atrioventricular valve formation7,11.

Partitioning of the primitive atrium begins at the end of the fourth gestational week through formation, modification, and subsequent fusion of the septum primum and septum secundum12. The primitive atrium division process is complex not only because the septus primum fuses with endocardial cushions, but also because permanent communication must exist to allow blood flow from the right to the left atrium12,13. The septum primum edge is attached to endocardial cushions, delimiting an interatrial communication called ostium or foramen primum, which disappears after fusion of the septum primum to the endocardial cushions12,13.

Before the ostium primum disappears, numerous perforations caused by programmed cell death develop at the center of septum primum, forming the ostium or foramen secundum, which serves as a shunt for oxygenated blood from the ductus venosus to pass from the right to the left atrium12. The septum secundum develops more slowly, to the right of the septum primum, migrating as the ostium primum closes and gradually overlapping the ostium secundum. Septum secundum separates the atria incompletely, thereby forming the foramen ovale13.

During intrauterine life, the foramen ovale allows most oxygenated blood entering the right atrium from the inferior vena cava and ductus venosus to pass into the left atrium. It also prevents blood from flowing in the opposite direction, because the septum primum closes against a relatively rigid septum secundum. After birth, the foramen ovale usually closes, and the interatrial septum completely separates atrial chambers12.

Cell analysis has demonstrated that, during the first developmental stages, septum primum has a muscular central portion in which myocytes are in close contact14. In addition to myocytes, there is also the aforementioned presence of mesenchymal tissue in the septum primum14-16. The septum primum is covered by the endocardium, which is made up of elongated and flattened cells17.

Color Doppler echocardiography has led to major advances in the field of fetal heart and circulatory physiology; therefore, understanding the functional mechanism of foramen ovale is of prime importance.

In earlier studies, our team analyzed septum primum mobility, its development during intrauterine life18, and its relationship with the presence of atrial extrasystoles19,20 and left ventricular diastolic function21. To evaluate septum primum excursion quantitatively at every cardiac cycle, its maximal excursion toward the left atrium is measured in a four-chamber view. An "excursion index" of septum primum was created to correlate its maximal excursion to left atrial diameter20,21.

This study aimed at describing morphological features of the interatrial septum in normal fetuses, especially foramen ovale and septum primum, to compare septum primum excursion with foramen ovale diameter.

Methods

For anatomical evaluation, both septum primum maximal excursion toward the left atrium and foramen ovale diameter were measured in the hearts of ten formaldehyde-preserved human fetuses (gestational ages between 28 and 36 weeks) from the Laboratório de Anatomia do Feto e do Recém-nascido do Departamento de Morfologia do Centro de Ciências da Saúde da Universidade (Fetal and New-born Anatomy Laboratory of the Morphology Department of the University’s Health Sciences Center).

Anatomical dissection was performed according to standard technique, with en bloc resection of the heart and lungs. The lungs were then resected at the level of the pulmonary hila, and the heart was cut transversely to the interventricular septum from the apex to the base, allowing ventricular cavities to be visualized by opening the atrial wall and exposing the septum primum, septum secundum, and foramen ovale. Septum primum maximal excursion and foramen ovale diameter were measured under a colposcope with 13x magnification using an adapted measurement device (a caliper with two sharp metal ends).

Septum primum excursion was measured by fixing one of the ends of the measurement device in the septum secundum and the other in the middle of the free edge of the septum primum, which was pushed toward the left atrium as far as its maximal excursion, without deforming neighboring structures.

Foramen ovale diameter was measured at a 90° angle in relation to the septum primum excursion measurement, corresponding to a line between septum primum implantation sites.

Histological sections were obtained from the foramen ovale, septum primum, septum secundum, left atrium, and right atrium. Subendocardial and subepicardial tissue slides were stained using the hematoxylin-eosin method and Goldner’s technique, in light green solution.

Results

The anatomical measurements of the formaldehyde-preserved fetal hearts are presented in Table 1.

Histological examination of septum primum and septum secundum from the base to the apex (longitudinal section) allowed identification of cardiac muscular fibers in both structures and, hence, the presence of contractility. It also enabled visualization of blood vessels supplying these sites, in addition to intramural nerves and neurons of the neurovegetative system. Figures 1 through 7 show the macroscopic and microscopic sections and their descriptions.


Discussion

During fetal life, septum primum acts as a valve that closes the foramen ovale when atrial contractions occur. During diastole, septum primum bulges into the left atrium, allowing maximal opening and right-to-left flow22,23.

In previous studies, our team evaluated septum primum echocardiographic behavior during fetal life. The relationship between septum primum mobility and the presence of atrial extrasystoles was assessed in a study comparing a group of fetuses with atrial extrasystoles and a control group of normal fetuses. The redundancy index (RI), defined as the ratio between septum primum maximal excursion and left atrial maximal diameter on fetal echocardiogram (four-chamber view), showed that septum primum is more redundant in fetuses with atrial extrasystoles during intrauterine life16.

Septum primum mobility has proved to be an indicator of left diastolic function. Taking into account that septum primum mobility may reflect changes related to left atrial pressure, alterations in left ventricular relaxation and/or compliance may affect the behavior of the former. With the use of groups of fetuses of diabetic mothers with septal myocardial hypertrophy as a model for decreased left ventricular compliance and relaxation it was noted that, in this situation, septum primum excursion is reduced. Septum primum may also develop hypertrophy. Therefore, the greater the myocardial hypertrophy in the interventricular septum, the more restricted the left ventricular filling and the shorter the septum primum excursion into the left atrium during the cardiac cycle20,21. In this same study, it has been suggested that septum primum excursion may be a more suitable index for ventricular diastolic function than those traditionally accepted, since it shows an inverse relationship with interventricular septal hypertrophy and is easier to perform than the atrioventricular valve flow analysis.

In an earlier study, it was also found that septum primum maximal excursion is increased during fetal breathing, a finding that was related to an increase in left ventricular distensibility due to respiratory movements24.

The most recent hypothesis raised by our team attempts to explore the notion that the morphological composition of septum primum would directly influence its echocardiographic behavior, most notably its mobility, thereby reflecting its excursion index.

Each stage during septum primum formation is directly related to its role in fetal heart circulation. Its histological structure directly affects its behavior on blood flow that cross the foramen ovale25,26.

Thus, it may be suggested that septum primum is active in character, and this behavior may influence the blood flow through the foramen ovale. Moreover, septum primum mobility itself, as well as its excursion into the left atrium, depends not only on left atrial pressure, but also on its muscle fibers.

Acknowledgements

We would like to thank Sérgio Oliveira Silveira, laboratory technician, Department of Morphology, CCS, UFSM.

Supported by: FAPERGS – Fundação de Amparo à Pesquisa do Estado do RS, CAPES and CNPq.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

References

Manuscript received June 18, 2006; revised manuscript received October 18, 2006; accepted November 10, 2006.

  • 1. De Haan RL. Morphogenesis. Annu Rev Physiol. 1964; 26: 15-46.
  • 2. De Haan RL. Morphogenesis of the vertebrate heart. In: Haan RL, Ursprung H, ed. Organogenesis. New York: Holt, Rinehart and Winston; 1965. p. 377-419.
  • 3. De Haan RL, Fujii S, Satin J. Cell interactions in cardiac development. Dev Growth Differ. 1990; 32: 233-41.
  • 4. Manasek FJ. The extracellular matrix: a dynamic component of the developing embryo. In: Moscona A, Monroy A, eds. Current topics in development biology. New York: Academic Press; 1975. p. 35-102.
  • 5. Icardo JM. Cardiac morphogenesis and development. Experientia. 1988; 44: 11-2.
  • 6. Icardo JM. Development biology of the vertebrate heart. J Exp Zool. 1996; 275: 144-61.
  • 7. Markwald R, Fitzharris T, Manasek F. Structural development of endocardial cushions. Am J Anat. 1977; 148: 85-120.
  • 8. Hay DA. Development and fusion of the endocardial cushion. In: Rosenquist GC, Bergfma D, eds. Birth defects, original articles. New York: Allan R Liss Inc.; 1978. p. 69-90. (Series XIV, nş 7).
  • 9. Bolender DL, Markwald RR. Epithelial-mesenchymal transformation in atrioventricular cushion tissue morphogenesis. Scanning Electron Microsc. 1979; 3: 313-22.
  • 10. Steding G, Seidl W. Contribution to the development of the heart. Part I: normal development. Thorac Cardiovasc Surg. 1980; 28: 386-409.
  • 11. Argüelo C, De La Cruz M, Sanchez M. Ultrastructural and experimental evidence of myocardial cell differentiation into connective tissue cell in embryonic chick heart. J Mol Cell Cardiol. 1978; 10: 307-15.
  • 12. Moore K, Persaud TVN. Sistema cardiovascular. In: Moore KL, Persaud TVN. Embriologia clínica. 6Ş ed. Rio de Janeiro: Guanabara Koogan; 2000. p. 332-82.
  • 13. Anderson RH, Webb S, Brown NA. Clinical anatomy of the atrial septum with reference to its developmental components. Clin Anat. 1999; 12: 362-74.
  • 14. Patten BM. The formation of the cardiac loop in the chick. Am J Anat. 1922; 30: 373-97.
  • 15. Patten BM, Kramer TC, Barry A. Valvular action in the embryonic chick heart by localized apposition of endocardial masses. Anat Rec. 1948; 102: 299-312.
  • 16. Arrechedera H, Alvarez M, Strauss M, Ayesta C. Origin of mesenchymal tissue in the septum primum: a structural and ultrastructural study. J Mol Cell Cardiol. 1987; 19: 641-51.
  • 17. Wessels A, Anderson RH, Markwald RR, Webb S, Brown NA, Viragh S, et al. Atrial development in the human heart: na immunohistochemical study with emphasis on the role of mesenchymal tissues. Anat Rec. 2000; 259 (3): 288-300.
  • 18. Zielinsky P, Firpo C, Martha VF, Silva ES. Estudo ecocardiográfico pré-natal da redundância do septum primum e sua relação com a gênese de extra-sístoles atriais no feto. Arq Bras Cardiol. 1995; 65: 153-7.
  • 19. Zielinsky P, Firpo C, Martha VF, Silva ES. Papel da membrana da fossa oval no desencadeamento de arritmias cardíacas fetais. Rev Bras Ginec Obstet. 1995; 17: 711-9.
  • 20. Firpo C, Zielinsky P. Mobility of the flap valve of the primary atrial septum in the developing human fetus. Cardiol Young. 1998; 8 (1): 67-70.
  • 21. Firpo C, Zielinsky P. Behavior of septum primum mobility in third-trimester fetuses with myocardial hypertrophy. Ultrasound Obstet Gynecol. 2003; 21: 445-50.
  • 22. Puerta Fonolla AJ, Orts Llorca F. Origin and development of the septo primeiro. Acta Anat (Basel). 1978; 100 (2): 250-7.
  • 23. Morse DE, Rogers CS, McCann PS. Atrial septation in the chick and rat: a review. J Submicrosc Cytol. 1984; 16: 259-72.
  • 24. Miyague NI, Ghidini A, Miyague LLT. Fetal breathing movements are associated with changes in compliance of the left ventricle. Fetal Diagn Ther. 1997; 12: 72-5.
  • 25. Anderson RH, Webb S, Brown NA. Clinical anatomy of the septum primum with reference to its developmental components. Clin Anat. 1999; 12: 362-74.
  • 26. Anderson RH, Webb S, Brown NA. Development of the heart: septation of the atriums and ventricles. Heart. 2003; 89: 949-58.
  • Mailing address:

    Luiz Henrique Nicoloso
    Av. Princesa Isabel, 370
    90620-001 – Porto Alegre, RS - Brazil
    E-mail:
  • Publication Dates

    • Publication in this collection
      15 June 2007
    • Date of issue
      May 2007

    History

    • Accepted
      10 Nov 2006
    • Reviewed
      18 Oct 2006
    • Received
      18 June 2006
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