The atrial septum enables efficient oxygen transport by separating the systemic and pulmonary venous blood returning to the heart. Only in placental mammals will the atrial septum form by the coming-together of the septum primum and the septum secundum. In up to one of four placental mammals, this complex morphogenesis is incomplete and yields patent foramen ovale. The incidence of incomplete atrial septum is unknown for groups with the septum primum only, such as birds and reptiles. We found a low incidence of incomplete atrial septum in 11 species of bird (0% of specimens) and 13 species of reptiles (3% of specimens). In reptiles, there was a trabecular interface between the atrial septum and the atrial epicardium which was without a clear boundary between left and right atrial cavities. In developing reptiles (four squamates and one crocodylian), the septum primum initiated as a sheet that acquired perforations and the trabecular interface developed late. We conclude that atrial septation from the septum primum only results in a low incidence of incompleteness. In reptiles, the atrial septum and atrial wall develop a trabecular interface, but previous studies on atrial hemodynamics suggest this interface has a very limited capacity for shunting.

Department of Bioscience Zoophysiology Aarhus University Aarhus Denmark

Department of Medical Biology Amsterdam Cardiovascular Sciences University of Amsterdam Amsterdam The Netherlands

Institute of Anatomy 1st Medical Faculty Czech Academy of Sciences Charles University and Institute of Physiology Prague Czech Republic

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Anderson, D. F. , Faber, J. J. , Morton, M. J. , Parks, C. M. , Pinson, C. W. , & Thornburg, K. L. (1985). Flow through the foramen ovale of the fetal and new‐born lamb. Journal of Physiology, 365, 29–40. PubMed PMC

Anderson, R. H. , Spicer, D. E. , Brown, N. A. , & Mohun, T. J. (2014). The development of septation in the four‐chambered heart. The Anatomical Record, 297(8), 1414–1429. 10.1002/ar.22949 PubMed DOI

de Bakker, D. M. , Wilkinson, M. , & Jensen, B. (2015). Extreme variation in the atrial septation of caecilians (Amphibia: Gymnophiona). Journal of Anatomy, 226(1), 1–12. 10.1111/joa.12255 PubMed DOI PMC

Boukens, B. J. D. , Kristensen, D. L. , Filogonio, R. , Carreira, L. B. T. , Sartori, M. R. , Abe, A. S. , … Jensen, B. (2019). The electrocardiogram of vertebrates: Evolutionary changes from ectothermy to endothermy. Progress in Biophysics and Molecular Biology, 144, 16–29. 10.1016/j.pbiomolbio.2018.08.005 PubMed DOI

Briggs, L. E. , Kakarla, J. , & Wessels, A. (2012). The pathogenesis of atrial and atrioventricular septal defects with special emphasis on the role of the dorsal mesenchymal protrusion. Differentiation, 84(1), 117–130. PubMed PMC

Burggren, W. , Farrell, A. , & Lillywhite, H. (1998). Vertebrate cardiovascularsystems, In Comprehensive Physiology (pp. 215–308). Wiley & Sons, Inc.

Burggren, W. W. , & Johansen, K. (1982). Ventricular hemodynamics in the monitor lizard Varanus exanthematicus: Pulmonary and systemic pressure separation. Journal of Experimental Biology, 96, 343–354.

Burggren, W. W. , & Johansen, K. (1986). Circulation and respiration in lungfishes (Dipnoi). Journal of Morphology, 190, 217–236.

Calvert, P. A. , Rana, B. S. , Kydd, A. C. , & Shapiro, L. M. (2011). Patent foramen ovale: Anatomy, outcomes, and closure. Nat.Rev.Cardiol. 8(3), 148–160. PubMed

Davies, F. , & Francis, E. T. B. (1941). The heart of the salamander (Salamandra salamandra, L.), with special reference to the conducting (connecting) system and its bearing on the phylogeny of the conducting systems of mammalian and avian hearts. Philosophical Transactions of the Royal Society of London.Series B, Biological Sciences, 231(578), 99–130.

Elliott, G. C. , Gurtu, R. , McCollum, C. , Newman, W. G. , & Wang, T. (2014). Foramen ovale closure is a process of endothelial‐to‐mesenchymal transition leading to fibrosis. PLOS One, 9(9), e107175. PubMed PMC

Franklin, K. J. , Amoroso, E. C. , Barclay, A. E. , & Prichard, M. M. L. (1942). The valve of the foramen ovale its relation to pulmonary vein entries. The Veterinary Journal (1900), 98(2), 29–41.

de Graaf, A. R. (1957). Investigations into the distribution of blood in the heart and aortic arches of Xenopus laevis (Daud.). Journal of Experimental Biology, 34(2), 143–172.

Greil, A. (1908). Entwickelungsgeschichte des Kopfes und des Blutgefässsystemes von Ceratodus forsteri. I. Gesammtenentwickelung bis zum Beginn der Blutzirkulation. Denkschriften der Medizinisch‐Naturwissenschaftlichen Gesellschaft zu Jena, 4, 661–934.

Greil, A. (1913). Entwickelungsgeschichte des Kopfes und des Blutgefässsystemes von Ceratodus forsteri. II. Die epigenetischen Erwerbungen während der Stadien 39‐48. Denkschriften der Medizinisch‐Naturwissenschaftlichen Gesellschaft zu Jena, 9, 935–1492.

Hagen, P. T. , Scholz, D. G. , & Edwards, W. D. (1984). Incidence and size of patent foramen ovale during the first 10 decades of life: An autopsy study of 965 normal hearts. Mayo Clin Proceedings, 59(1), 17–20. PubMed

Hara, H. , Virmani, R. , Ladich, E. , Mackey‐Bojack, S. , Titus, J. L. , Karnicki, K. , … Schwartz, R. S. (2007). Patent foramen ovale: Standards for a preclinical model of prevalence, structure, and histopathologic comparability to human hearts. Catheterization and Cardiovascular Interventions, 69(2), 266–273. 10.1002/ccd.20973 PubMed DOI

Hendrix, M. J. , & Morse, D. E. (1977). Atrial septation. I. Scanning electron microscopy in the chick. Developmental Biology, 57(2), 345–363. PubMed

Hanemaaijer, J. , Gregorovicova, M. , Nielsen, J. M. , Moorman, A. F. , Wang, T. , Planken, R. N. , Christoffels, V. M. , Sedmera, D. , & Jensen, B. (2019). Identification of the building blocks of ventricular septation in monitor lizards (Varanidae). Development, 146(14), dev177121. PubMed

van den Hoff, M. J. B. , Kruithof, B. P. T. , Moorman, A. F. M. , Markwald, R. R. , & Wessels, A. (2001). Formation of myocardium after the initial development of the linear heart tube. Developmental Biology, 240(1), 61–76. 10.1006/dbio.2001.0449 PubMed DOI

Hoffman, J. I. , & Kaplan, S. (2002). The incidence of congenital heart disease. Journal of American College of Cardiology, 39(12), 1890–1900. PubMed

Icardo, J. M. , Ojeda, J. L. , Colvee, E. , Tota, B. , Wong, W. P. , & Ip, Y. K. (2005). Heart inflow tract of the African lungfish Protopterus dolloi . Journal of Morphology, 263(1), 30–38. PubMed

Jay, P. Y. , Degenhardt, K. R. , & Anderson, R. H. (2016). Molecular pathways and animal models of atrial septal defect. In Rickert‐Sperling, S. , Kelly, G. R. , & Driscoll, J. D. (Eds.), Congenital Heart Diseases: The Broken Heart: Clinical Features, Human Genetics and Molecular Pathways (pp. 291–300). Vienna: Springer Vienna.

Jensen, B. , van den Berg, G. , van den Doel, R. , Oostra, R. J. , Wang, T. , & Moorman, A. F. M. (2013). Development of the hearts of lizards and snakes and perspectives to cardiac evolution. PLOS One, 8(6), e63651. PubMed PMC

Jensen, B. , Boukens, B. J. , Crossley, D. A. , Conner, J. , Mohan, R. A. , van Duijvenboden, K. , … Christoffels, V. M. (2018). Specialized impulse conduction pathway in the alligator heart. eLife, 7. PubMed PMC

Jensen, B. , Boukens, B. J. D. , Postma, A. V. , Gunst, Q. D. , van den Hoff, M. J. B. , Moorman, A. F. M. , … Christoffels, V. M. (2012). Identifying the evolutionary building blocks of the cardiac conduction system. PLOS One, 7(9), e44231. 10.1371/journal.pone.0044231 PubMed DOI PMC

Jensen, B. , Moorman, A. F. M. , & Wang, T. (2014). Structure and function of the hearts of lizards and snakes. Biological Reviews of the Cambridge Philosophical Society, 89(2), 302–336. 10.1111/brv.12056 PubMed DOI

Jensen, B. , Vesterskov, S. , Boukens, B. J. , Nielsen, J. M. , Moorman, A. F. M. , Christoffels, V. M. , & Wang, T. (2017). Morpho‐functional characterization of the systemic venous pole of the reptile heart. Scientific Reports, 7(1), 6644. 10.1038/s41598-017-06291-z PubMed DOI PMC

Jensen, B. , Wang, T. , & Moorman, A. F. M. (2019). Evolution and development of the atrial septum. The Anatomical Record, 302(1), 32–48. PubMed PMC

Johansen, K. , & Burggren, W. W. (1980). Cardiovasular function in the lower vertebrates. Hearts and Heart‐like Organs, 1, 61–117.

Joyce, W. , Axelsson, M. , Altimiras, J. , & Wang, T. (2016). In situ cardiac perfusion reveals interspecific variation of intraventricular flow separation in reptiles. The Journal of Experimental Biology, 219(Pt 14), 2220–2227. 10.1242/jeb.139543 PubMed DOI

Joyce, W. , Axelsson, M. , & Wang, T. (2017). Autoregulation of cardiac output is overcome by adrenergic stimulation in the anaconda heart. The Journal of Experimental Biology, 220(Pt 3), 336–340. 10.1242/jeb.149237 PubMed DOI

Joyce, W. , Crossley, D. A. , Wang, T. , & Jensen, B. (2019). Smooth muscle in cardiac chambers is common in turtles and extensive in the emydid turtle, Trachemys scripta. The Anatomical Record, 10.1002/ar.24257 PubMed DOI PMC

Khan, R. , & Jay, P. Y. (2016). Human genetics of atrial septal defect. In Rickert‐Sperling S., Kelly G. R., & Driscoll J. D. (Eds.), Congenital Heart Diseases: The Broken Heart: Clinical Features, Human Genetics and Molecular Pathways (pp. 279–290). Vienna, Austria: Springer Vienna.

Kiserud, T. (2005). Physiology of the fetal circulation. Seminars in Fetal and Neonatal Medicine, 10(6), 493–503. 10.1016/j.siny.2005.08.007 PubMed DOI

Klitgaard, T. (1978). Morphology and histology of the heart of the Australian Lungfish, Neoceratodus‐Forsteri (Krefft). Acta Zoologica, 59(3‐4), 187–198.

Kroneman, J. G. H. , Faber, J. W. , Schouten, J. C. M. , Wolschrijn, C. F. , Christoffels, V. M. , & Jensen, B. (2019). Comparative analysis of avian hearts provides little evidence for variation among species with acquired endothermy. Journal of Morphology, 280, 395–410. 10.1002/jmor.20952 PubMed DOI PMC

Kvasilova, A. , Gregorovicova, M. , Kundrat, M. , & Sedmera, D. (2019). HNK‐1 in morphological study of development of the cardiac conduction system in selected groups of sauropsida. The Anatomical Record, 302(1), 69–82. 10.1002/ar.23925 PubMed DOI

Lang, J. W. , & Andrews, H. V. (1994). Temperature‐dependent sex determination in crocodilians. Journal of Experimental Zoology, 270(1), 28–44. PubMed

LekanneDeprez, R. H. , van den Hoff, M. J. B. , de Boer, P. A. J. , Ruijter, J. M. , Maas, A. A. W. , Chamuleau, R. A. F. M. , … Moorman, A. F. M. (1998). Changing patterns of gene expression in the pulmonary trunk‐banded rat heart. Journal of Molecular and Cellular Cardiology, 30(9), 1877–1888. PubMed

Lewis, Z. R. , & Hanken, J. (2017). Convergent evolutionary reduction of atrial septation in lungless salamanders. Journal of Anatomy, 230(1), 16–29. PubMed PMC

Macdonald, A. A. , Carr, P. A. , & Currie, R. J. W. (2007). Comparative anatomy of the foramen ovale in the hearts of cetaceans. Journal of Anatomy, 211(1), 64–77. PubMed PMC

Mommersteeg, M. T. M. , Soufan, A. T. , de Lange, F. J. , van den Hoff, M. J. B. , Anderson, R. H. , Christoffels, V. M. , & Moorman, A. F. M. (2006). Two distinct pools of mesenchyme contribute to the development of the atrial septum. Circulation Research, 99(4), 351–353. PubMed

Moorman, A. F. M. , Houweling, A. C. , de Boer, P. A. J. , & Christoffels, V. M. (2001). Sensitive nonradioactive detection of mRNA in tissue sections: Novel application of the whole‐mount in situ hybridization protocol. The Journal of Histochemistry and Cytochemistry, 49(1), 1–8. PubMed

Murakami, T. , Hagio, M. , & Nakai, M. (1990). Anatomical closure of the foramen ovale in cattle. Advances in Animal Cardiology, 23(23), 23–28.

Nakanishi, K. , Yoshiyama, M. , & Homma, S. (2017). Patent foramen ovale and cryptogenic stroke. Trends in Cardiovascular Medicine, 27, 575–581. 10.1016/j.tcm.2017.06.016 PubMed DOI

Perry, S. F. , & Sander, M. (2004). Reconstructing the evolution of the respiratory apparatus in tetrapods. Respiratory Physiology & Neurobiology, 144(2‐3), 125–139. PubMed

Pizzi, R. , Pereira, Y. M. , Rambaud, Y. F. , Strike, T. , Flach, E. , Rendle, M. , & Routh, A. (2009). Secundum atrial septal defect in a Komodo dragon (Varanus komodoensis). The Veterinary Record, 164(15), 472–473. PubMed

Robertson, J. I. (1913). The development of the heart and vascular system of Lepidosiren paradoxa . In Quart.J.Micr.Sci. (Vol. 59, 53‐132). (Reprinted from: Not in File).

Rowlatt, U. (1990). Comparative anatomy of the heart of mammals. Zoological Journal of the Linnean Society, 98(1), 73–110.

Rowlatt, U. , & Gaskin, D. E. (1975). Functional anatomy of the heart of the harbor porpoise, Phocaena phocaena. Journal of Morphology, 146(4), 479–493. 10.1002/jmor.1051460405 PubMed DOI

Runciman, S. I. C. , Gannon, B. J. , & Baudinette, R. V. (1995). Central cardiovascular shunts in the perinatal marsupial. Anatomical Record, 243(1), 71–83. 10.1002/ar.1092430109 PubMed DOI

Röse, C. (1890). Beitrage zur vergleichenden Anatomie des Herzens der Wirbelthiere. Morphol.Jahrb, 16, 27–96.

Sedmera, D. , Reckova, M. , DeAlmeida, A. , Sedmerova, M. , Biermann, M. , Volejnik, J. , … Thompson, R. P. (2003). Functional and morphological evidence for a ventricular conduction system in zebrafish and Xenopus hearts. American Journal of Physiology‐Heart and Circulatory Physiology, 284(4), H1152–H1160. PubMed

Sedmera, D. , Wessels, A. , Trusk, T. C. , Thompson, R. P. , Hewett, K. W. , & Gourdie, R. G. (2006). Changes in activation sequence of embryonic chick atria correlate with developing myocardial architecture. American Journal of Physiology‐Heart and Circulatory Physiology, 291(4), H1646–H1652. PubMed

Snarr, B. S. , O'Neal, J. L. , Chintalapudi, M. R. , Wirrig, E. E. , Phelps, A. L. , Kubalak, S. W. , & Wessels, A. (2007). Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development. Circulation Research, 101(10), 971–974. PubMed

Steimle, J. D. , Rankin, S. A. , Slagle, C. E. , Bekeny, J. , Rydeen, A. B. , Chan, S. S. K. , … Moskowitz, I. P. (2018). Evolutionarily conserved Tbx5‐Wnt2/2b pathway orchestrates cardiopulmonary development. Proceedings of the National Academy of Sciences of the United States of America, 115(45), E10615–E10624. PubMed PMC

Sweeney, L. J. , & Rosenquist, G. C. (1979). The normal anatomy of the atrial septum in the human heart. American Heart Journal, 98(2), 194–199. PubMed

Sylva, M. , van den Hoff, M. J. B. , & Moorman, A. F. M. (2014). Development of the human heart. American Journal of Medical Genetics, 164A(6), 1347–1371. PubMed

Taussig, H. B. (1988). Evolutionary origin of cardiac‐malformations. Journal of the American College of Cardiology, 12(4), 1079–1086. PubMed

Tudora, D. C. (1979). Congenital defects of poultry. World's Poultry Science Journal, 35(1), 20–26. 10.1079/WPS19790003 DOI

Wang, T. , Altimiras, J. , & Axelsson, M. (2002). Intracardiac flow separation in an in situ perfused heart from Burmese python Python molurus . Journal of Experimental Biology, 205(17), 2715–2723. PubMed

Webb, G. J. W. (1979). Comparative cardiac anatomy of the Reptilia. III. The heart of crocodilians and an hypothesis on the completion of the interventricular septum of crocodilians and birds. Journal of Morphology, 161(2), 221–240. PubMed

Webb, S. , Kanani, M. , Anderson, R. H. , Richardson, M. K. , & Brown, N. A. (2001). Development of the human pulmonary vein and its incorporation in the morphologically left atrium. Cardiology in the Young, 11(6), 632–642. PubMed

Wessels, A. (2016). Inflow tract development. In Rickert‐Sperling S., Kelly R. G., & Driscoll D. J. (Eds.), Congenital Heart Diseases: The Broken Heart: Clinical Features, Human Genetics and Molecular Pathways (pp. 55–62). Vienna, Austria: Springer Vienna.

Wessels, A. , Anderson, R. H. , Markwald, R. R. , Webb, S. , Brown, N. A. , Viragh, S. , … Lamers, W. H. (2000). Atrial development in the human heart: An immunohistochemical study with emphasis on the role of mesenchymal tissues. Anatomical Record, 259(3), 288–300. PubMed

Hemodynamics During Development and Postnatal Life

Cor Triatriatum Dexter Associated with an Ostium Primum Atrial Defect and Left-Sided Opening of the Coronary Sinus in a Stillborn Fetus