Early electron microscopic studies shed considerable light on the development o f the intercalated disk in small mammals (McNutt, 1970), demonstrating that in fetal life the fasciae adhérentes, into which the myofilaments insert, are initially independent o f the gap junctions. What was not evident, however, was the overall distribution o f these junction types over the surface o f individual cells or throughout intact myocardium, and the changing postnatal distribution that the present study has revealed. It was postulated that the mechanical tension o f the increasing number o f myofilaments inserting into the fasciae adhérentes explains the predominantly transverse orientation o f these junctions within the mature intercalated disk, which was considered to be present from birth in man. If, as shown in the present study, coalescence o f the specialised intercellular junction types into the mature intercalated disk does not occur until about 6 years o f age, and, therefore, long after establishment o f postnatal haemodynamics and mechanical loading and after most o f the cardiac growth has taken place, it seems unlikely that the stimulus to fascia adherens reorientation is simply mechanical. This alteration may serve
a functional role, and it is tempting to suggest that the immature junctional distribution may optimise mechanical, electrical and chemical intercellular communication during the periods o f adaptation to postnatal haemodynamics and rapid myocardial growth, and that the determinants o f the progressive change in distribution are more complex.
4 .4 .4 Ventricular growth
The diameter o f cardiac myocytes increases postnatally by a factor o f about 2.4, with greater than 90% o f human myocardial growth resulting from such cellular enlargement (Zak, 1974). However, cardiac myocytes retain the capacity for mitotic division for about the first 6 months o f postnatal life in man (Zak, 1974; Yasui et al. 1989), during which time hyperplasia accounts for a significant proportion o f the ventricular growth. The cellular basis o f myocardial growth, therefore, depends on age (Zak, 1974), but a longstanding and hitherto unanswered question is how the heart can maintain its overall geometry and pumping function, whilst growing rapidly.
Richter (1974) referred to the heart as a "topological manifold" in which changes in the surface area and configuration o f any cardiac myocyte must affect the cell surface configurations o f its neighbours. At that time, he made the largely correct assumption that the adaptive processes o f myocardial growth are governed by intercellular information transfer via gap junctions, also essential for electrical propagation. Richter postulated that although considerable configurational changes occurred between individual myocytes, there were "invariants in the surface topology" o f the specialised intercellular junctions, which would maintain the same position with respect to each other, the cell surface and the surfaces o f adjacent cells, throughout growth. Thus, he postulated that gap junctions not only played an important part in intercellular communication governing patterns o f growth, but, with this growth, they were the invarying points o f contact and coupling between cells. By demonstrating that the positions o f the junctions change markedly with postnatal development, the present study also demonstrates that this postulate is incorrect. In terms o f the "topological manifold", however, the infantile junctional pattern may be the means by which the massively growing heart, undergoing hyperplastic as well as hypertrophic enlargement, can maintain the required communicating and adhering contacts between the component myocytes despite the configurational changes. This junctional pattern will influence the mechanical and electrical properties o f the immature myocardium.
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myocardium (Van Hare et al. 1990), significant changes in neonatal ventricular form and mass can occur within 2-3 days o f the onset o f haemodynamic changes (Belik and Light, 1989). The ability o f myocardium to adapt and remodel appropriately to the physiological changes o f infancy, whilst maintaining electrical and mechanical coupling, may depend on an appropriate pattern o f intercellular adhesion and communication in the early period o f rapid growth, with subsequent change to the mature adult pattern. The junctional distribution o f early infancy demonstrated in the present study may, at least in part, be responsible for permitting the substantial and rapid changes in myocardial architecture during this period.
4.4 .5 Potential implications for the timing o f surgery in children
The pattern o f intercellular coupling and adhesion demonstrated in this study is likely to be associated with alterations in the functional anisotropy o f the tissue, including the directional ease and rates o f intercellular diffusion o f the small molecules regulating growth, tissue differentiation and maturation (Warner et al. 1984; Green, 1988). The arrangement o f communicating and adherens intercellular junctions that exists at birth may best fulfil the requirements o f the growing and adapting ventricular myocardium. Progressive change toward the arrangement in the adult ventricle throughout early childhood may not only meet the more stable requirements o f the older ventricle, but may also render the myocardium less able to adapt appropriately to altered haemodynamics, and may be o f relevance to the timing o f cardiac surgery. Despite the increased complications o f cardiopulmonary bypass and operative ischaemia in younger infants, corrective surgery for a variety o f congenital cardiac anomalies, when performed early in infant or even neonatal life, may improve long term cardiac performance, both mechanical (Kirklin et al. 1986; Gustafson et al. 1988; Colan et al. 1988; Norwood et al. 1988; Losay et al. 1992) and electrical (Walsh et al. 1988). Although the reason for the benefit from early reparative surgery may, in part, be due to reducing the duration o f exposure o f the myocardium to the adverse haemodynamics before correction, it is likely that other factors are important. Even when early preparative surgery is performed to improve the haemodynamic loading o f cardiac chambers before a delayed definitive repair, thereby reducing, but not eliminating, the requirement for later myocardial adaptive remodelling, the longterm results from such two-stage repairs may not be as good as early immediate correction (Danford et al. 1985; Colan et al. 1988; Yasui et al. 1989). One might speculate that the distribution o f intercellular junctions o f early infancy
may not only facilitate myocardial adaptation to the changing loads and stresses accompanying the physiological circulatory alterations early in life, but may also confer greater adaptive potential after surgery.
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