BACKER, A.E.

PEXIEDER, T.

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European Heart Journal (1984) 5,180-182European Society of Cardiology Working Group onEmbryology and TeratologyThe first meeting of the working group was held 4and 5 November 1982 at Alderley Park, Maccles-field, U.K., by kind permission of Imperial Chemi-cal Industries PLC. It was attended by 24 memberswho had been invited by the Chairmen (ProfessorsA. E. Becker and T. Pexieder) as representing theactive centres for Cardiac Embryology withinEurope. The programme had been arranged by theLocal Organizer, Professor R. H. Anderson, so asto stimulate discussion and to lead the way towardsa programme for cooperative research into thedevelopment and structure of the heart.Nomenclature of the embryonic heartThe opening session was concerned with thenomenclature of the embryonic heart and itscorrelation with cardiac morphology. ProfessorAnderson led off with an account of the value ofdescriptive nomenclature in the formed heart. Theproblems inherent in the use of nominative termsin embryology were then highlighted by ProfessorPexieder, who recounted the many and variedterms used to describe the developing heart. Heshowed how the use of the same term for differentpurposes by different investigators self-evidently ledto confusion, in many instances underscoring con-troverses which were more apparent than real. Thisled to discussion about the need to separate the dif-ferent phases of cardiac development, and to avoidusing potentially confusing terms (e.g. bulbus). Alsoconsiderable differences between the animal speciesused for study were emphasized. The formulationof a nomenclature proposal was therefore held overfor the final session.Derivation of the different portions of theembryonic heartDr M. V. de la Cruz described her markingexperiments, derived from those of Rychter, andillustrated how they had shown the five-chamberconcept of the developing chick heart to be sim-plistic. Professor J. A. Los then showed how thevery use of the term 'segment' was inappropriateas generally used in embryology. The problem ofboundaries' of structures was aired. It was agreedthat chosen terms must be practical, and that theyshould not lead to a potential conflict with termsused for the formed normal heart, nor should theyimply any causal relationship until this was proven.It was recognized that different terms would likelybe required for the different stages of growth.Ventricular septationProfessor Becker opened with an account of thedefinitive septum, showing how the tripartiteapproach to description simplified categorization ofseptal defects. Dr A. C. G. Wenink then gave anaccount of his recent studies of the development ofthe ventricular septum, introducing the concept ofa primary muscular septum subsequently joined byinlet and outlet muscular structures before thewhole septation process was completed by elab-oration of the membranous septum. This wasfollowed by a detailed analysis by Dr M. Arteaga ofthe contribution of the atrioventricular endocardialcushions to the muscular ventricular septum in thechick. Convincing evidence was provided by usingIndian ink marking techniques. Discussionfollowed two main lines, one being the differencesbetween bird and mammalian hearts and the otherthe reliability of the marking technique.Ventricular septal defectsDr A. Gittengerger-de-Groot showed how theconcept of Dr Wenink accounted well for the manytypes of ventricular septal defect, particularly thosewhich illustrated non-fusion or malalignment of thedifferent components of the muscular septum. Dis-cussion emphasized that development of the atrio-ventricular valves was a late event, occurring quitesome time after the completion of ventricular sep-tation. Dr Wenink then further developed thistheme in the setting of atrioventricular septaldefects ('atrioventricular canal malformations').Professor Pexieder concluded the session by des-cribing Rychter's experimental production of septaldefects in the chick heart. He further comparedtheir pathogenesis with that of other animal models(Keeshond dog, fetal mouse trisomy and drug-induced CHD).Outflow portion 1Professor Pexieder opened the discussion in theEmbryology and teratology 181first session of the second day devoted to develop-ment of the left ventricular outflow tract. By pre-senting scanning electron micrographs of stagedhuman embryos he demonstrated conclusively thatclosure of the embryonic interventricular foramenat the same time moulded the outflow tract fromleft ventricle to aorta. No active process of transferwas involved. The subsequent discussion high-lighted the significance of the relative size ofstructures and their change with development andgrowth of the heart. The embryonic interventricu-lar foramen never closed, but became moulded intothe sub-aortic outflow tract. Professor W. Berschfollowed with an account of the vectorial torsionhypothesis of Doerr and Goertler. He explainedhow the approach had been one of theoretical con-cept rather than anatomic reality. He agreed withProfessor Pexieder that there was little evidence, orindeed need, to substantiate shrinkage of the out-flow tract during incorporation of the aorta into theleft ventricle. A series of slides presented by Pro-fessor G. Steding gave a different view of develop-ment of the outflow tract, not far removed from thatof Dr Wenink. The crucial point which remainedunanswered was the precise fashion in which theright atrium became connected to the right ven-tricle and consonant with this, the developingrelationship between the tricuspid valve and theventricular septum. This discussion was immedi-ately followed by the demonstration by ProfessorF. Orts Llorca of a human embryo with completetransposition. It was pointed out that the problemwith disagreements concerning its morphogenesis isrelated to the absence of a good animal model.Arterial portionThe final series of presentations was devoted tothe arterial pole of the heart. Dr H. M. Laane illus-trated the confusion which arose through impreciseuse of different descriptive terms. He then showedthe results of his own studies on septation of thearterial trunks and the ventricular outflow tracts.The role of the truncus and the aortic sac indevelopment of the great arteries was discussed.Professor Anderson then gave an account of how,for the formed heart, the distinction of ventriculo-arterial connexions, arterial relationships andinfundibular morphology had greatly simplified thedescription of so-called cono-truncal malfor-mations. Professor Pexieder recognized the value ofthis approach for the formed heart, but felt thatembryology was insufficiently advanced at thisstage to identify the fate of any embryonic cardiacstructure. Finally, Professor P. Krediet presentedhis work concerning the importance of haemo-dynamic factors. In his opinion, they were largelyresponsible for shaping many of the developmentalprocesses previously discussed. The concepts hedeveloped were based upon the interplay of twointertwining blood streams. Professor Los agreedthat the crossing of the blood streams was essentialfor the development of the aortic-pulmonaryseptum.Summing upOn this note the delegates moved to a final dis-cussion so as to sum up the progress made duringthe meeting. It was agreed that during prenatalcardiac development there was a need to separatethe stages of organogenesis and fetal growth. Thedivision point was proposed as completion ofventricular septation.The second summation related to the dangers ofextrapolating from studies of formed and mal-formed hearts to establish concepts of development.It was argued there was equal danger in extrapol-ating from normal embryogenesis to explain fetalmalformations. With these caveats in mind, bothfacets could be approached with an open mind.When speculations were made, they should beclearly identified as such.The third point was to identify areas for intensivefuture studies. It was agreed that while there wasnow consensus concerning the connexion of theaorta to the left ventricle, the precise mechanics ofarterial pole septation remained to be fully eluci-dated. Above all, the area which required concen-trated study was the development of the rightatrioventricular orifice and the origin of the inletseptum. It was resolved that these areas would bethe topics for further presentation at the meeting ofthe working group scheduled at Spa, Belguim, inSeptember 1983.Finally, it was unanimously agreed that there wasa need for a unified nomenclature to describe thedeveloping heart. The two approaches consideredwere either to develop a new language completely,or else to take the existing terms, eradicate thosewhich were considered unsuitable and to defineprecisely the suitable ones. While it was acceptedthat it would be difficult to create a totally newlanguage, it was also agreed that most of the termsextant were more or less unsatisfactory. It wasaccepted that further discussions at this stage of182 Embryology and teratologythe meeting were unlikely to prove constructive.Professor Pexieder therefore agreed to construct adraft nomenclature would be circulated to all mem-bers. Further discussion could then take place bycorrespondence and during the Spa meeting.A symposium on clinically relevant cardiacembryology and teratology will be held during theEuropean Congress of Cardiology in Dusseldorfduring July 1984. The working group which willpresent this symposium, at present has about 30members from most European countries. Any otherinvestigator interested in joining this group shouldcontact either Professor Becker or ProfessorPexieder.A. E. BECKERAcademisch Ziekenhuisbij de Universiteit vanAmsterdam,PathologieH2-135,Meibergdree/9,NL-1105 AZ Amsterdam,The NetherlandsT. PEXIEDERInstitut d'Histologie eld'Embryologie,rue du Bugnon 9,1011 Lausanne-Chuv,Switzerland

European Society of Cardiology Working Group on Embryology and Teratology

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