The heart in higher vertebrates develops from a simple tube into a complex organ with four chambers specialized for efficient pumping at pressure. During this period, there is a concomitant change in the level of myocardial organization. One important event is the emergence of trabeculations in the luminal layers of the ventricles, a feature which enables the myocardium to increase its mass in the absence of any discrete coronary circulation. In subsequent development, this trabecular layer becomes solidified in its deeper part, thus increasing the compact component of the ventricular myocardium. The remaining layer adjacent to the ventricular lumen retains its trabeculations, with patterns which are both ventricle‐ and species‐specific. During ontogenesis, the compact layer is initially only a few cells thick, but gradually develops a multilayered spiral architecture. A similar process can be charted in the atrial myocardium, where the luminal trabeculations become the pectinate muscles. Their extent then provides the best guide for distinguishing intrinsically the morphologically right from the left atrium. We review the variations of these processes during the development of the human heart and hearts from commonly used laboratory species (chick, mouse, and rat). Comparison with hearts from lower vertebrates is also provided. Despite some variations, such as the final pattern of papillary or pectinate muscles, the hearts observe the same biomechanical rules, and thus share many common points. The functional importance of myocardial organization is demonstrated by lethality of mouse mutants with perturbed myocardial architecture. We conclude that experimental studies uncovering the rules of myocardial assembly are relevant for the full understanding of development of the human heart. Anat Rec 258:319–337, 2000.

The combination of optical clarity and large scale of mutants makes the zebrafish vital for developmental biologists. However, there is no comprehensive reference of morphology and function for this animal. Since study of gene expression must be integrated with structure and function, we undertook a longitudinal study to define the cardiac morphology and physiology of the developing zebrafish. Our studies included 48‐hr, 5‐day, 2‐week, 4‐week, and 3‐month post‐fertilization zebrafish. We measured ventricular and body wet weights, and performed morphologic analysis on the heart with H&E and MF‐20 antibody sections. Ventricular and dorsal aortic pressures were measured with a servonull system. Ventricular and body weight increased geometrically with development, but at different rates. Ventricle‐to‐body ratio decreased from 0.11 at 48‐hr to 0.02 in adult. The heart is partitioned into sinus venosus, atrium, ventricle, and bulbus arteriosus as identified by the constriction between the segments at 48‐hr. Valves were formed at 5‐day post‐fertilization. Until maturity, the atrium showed extensive pectinate muscles, and the atrial wall increased to two to three cell layers. The ventricular wall and the compact layer increased to three to four cell layers, while the extent and complexity in trabeculation continued. Further thickening of the heart wall was mainly by increase in cell size. The bulbus arteriosus had similar characteristics to the myocardium in early stages, but lost the MF‐20 positive staining, and transitioned to smooth muscle layer. All pressures increased geometrically with development, and were linearly related to stage‐specific values for body weight (P < 0.05). These data define the parameters of normal cardiac morphology and ventricular function in the developing zebrafish. Anat Rec 260:148–157, 2000.

Because of the increasing availability of tools for genetic manipulation, the mouse has become the most popular animal model for studying normal and abnormal cardiac development. However, despite the enormous advances in mouse genetics, which have led to the production of numerous mutants with cardiac abnormalities resembling those seen in human congenital heart disease, relatively little comparative work has been published to demonstrate the similarities and differences in the developmental cardiac anatomy in both species. In this review we discuss some aspects of the comparative anatomy, with emphasis on the atrial anatomy, the valvuloseptal complex, and ventricular myocardial development. From the data presented it can be concluded that, apart from the obvious differences in size, the mouse and human heart are anatomically remarkably similar throughout development. The partitioning of the cardiac chambers (septation) follows the same sequence of events, while also the maturation of the cardiac valves and myocardium is quite similar in both species. The major anatomical differences are seen in the venous pole of the heart. We conclude that, taking note of the few anatomical “variations,” the use of the mouse as a model system for the human heart is warranted. Thus the analysis of mouse mutants with impaired septation will provide valuable information on cellular mechanisms involved in valvuloseptal morphogenesis (a process often disrupted in congenital heart disease), while the study of embryonic lethal mouse mutants that present with lack of compaction of ventricular trabeculae will ultimately provide clues on the etiology of this abnormality in humans.

Congenital coronary artery anomalies are of major significance in clinical cardiology and cardiac surgery due to their association with myocardial ischaemia and sudden death. Such anomalies are detectable by imaging modalities and, according to various definitions, their prevalence ranges from 0.21 to 5.79%. This consensus document from the Development, Anatomy and Pathology Working Group of the European Society of Cardiology aims to provide: (i) a definition of normality that refers to essential anatomical and embryological features of coronary vessels, based on the integrated analysis of studies of normal and abnormal coronary embryogenesis and pathophysiology; (ii) an animal model-based systematic survey of the molecular and cellular mechanisms that regulate coronary blood vessel development; (iii) an organization of the wide spectrum of coronary artery anomalies, according to a comprehensive anatomical and embryological classification scheme; (iv) current knowledge of the pathophysiological mechanisms underlying symptoms and signs of coronary artery anomalies, with diagnostic and therapeutic implications. This document identifies the mosaic-like embryonic development of the coronary vascular system, as coronary cell types differentiate from multiple cell sources through an intricate network of molecular signals and haemodynamic cues, as the necessary framework for understanding the complex spectrum of coronary artery anomalies observed in human patients.

Zebrafish and Xenopus have become popular model organisms for studying vertebrate development of many organ systems, including the heart. However, it is not clear whether the single ventricular hearts of these species possess any equivalent of the specialized ventricular conduction system found in higher vertebrates. Isolated hearts of adult zebrafish ( Danio rerio) and African toads ( Xenopus laevis) were stained with voltage-sensitive dye and optically mapped in spontaneous and paced rhythms followed by histological examination focusing on myocardial continuity between the atrium and the ventricle. Spread of the excitation wave through the atria was uniform with average activation times of 20 ± 2 and 50 ± 2 ms for zebrafish and Xenopus toads, respectively. After a delay of 47 ± 8 and 414 ± 16 ms, the ventricle became activated first in the apical region. Ectopic ventricular activation was propagated significantly more slowly (total ventricular activation times: 24 ± 3 vs. 14 ± 2 ms in zebrafish and 74 ± 14 vs. 35 ± 9 ms in Xenopus). Although we did not observe any histologically defined tracts of specialized conduction cells within the ventricle, there were trabecular bands with prominent polysialic acid-neural cell adhesion molecule staining forming direct myocardial continuity between the atrioventricular canal and the apex of the ventricle; i.e., the site of the epicardial breakthrough. We thus conclude that these hearts are able to achieve the apex-to-base ventricular activation pattern observed in higher vertebrates in the apparent absence of differentiated conduction fascicles, suggesting that the ventricular trabeculae serve as a functional equivalent of the His-Purkinje system.