Revisiting the anatomy of the right ventricle in the light of knowledge of its development

Controversies continue regarding several aspects of the anatomy of the morphologically right ventricle. There is disagreement as to whether the ventricle should be assessed in bipartite or tripartite fashion, and the number of leaflets to be found in the tricuspid valve. In particular, there is no agreement as to whether a muscular outlet septum is present in the normally constructed heart, nor how many septal components are to be found during normal development. Resolving these issues is of potential significance to those investigating and treating children with congenitally malformed hearts. With all these issues in mind, we have revisited our own experience in investigating the development and morphology of the normal right ventricle. To assess development, we have examined a large number of datasets, prepared by both standard and episcopic microscopy, from human and murine embryos. In terms of gross anatomy, we have compared dissections of normal autopsied hearts with virtual dissections of datasets prepared using computed tomography. Our developmental and postnatal studies, taken together, confirm that the ventricle is best assessed in tripartite fashion, with the three parts representing its inlet, apical trabecular, and outlet components. The ventricular septum, however, has only muscular and membranous components. The muscular part incorporates a small component derived from the muscularised fused proximal outflow cushions, but this part cannot be distinguished from the much larger part that is incorporated within the free-standing muscular infundibular sleeve. We confirm that the tricuspid valve itself has three components, which are located inferiorly, septally, and antero-superiorly.<br/

Revisiting the anatomy of the right ventricle in the light of knowledge of its development

Controversies continue regarding several aspects of the anatomy of the morphologically right ventricle. There is disagreement as to whether the ventricle should be assessed in bipartite or tripartite fashion, and the number of leaflets to be found in the tricuspid valve. In particular, there is no agreement as to whether a muscular outlet septum is present in the normally constructed heart, nor how many septal components are to be found during normal development. Resolving these issues is of potential significance to those investigating and treating children with congenitally malformed hearts. With all these issues in mind, we have revisited our own experience in investigating the development and morphology of the normal right ventricle. To assess development, we have examined a large number of datasets, prepared by both standard and episcopic microscopy, from human and murine embryos. In terms of gross anatomy, we have compared dissections of normal autopsied hearts with virtual dissections of datasets prepared using computed tomography. Our developmental and postnatal studies, taken together, confirm that the ventricle is best assessed in tripartite fashion, with the three parts representing its inlet, apical trabecular, and outlet components. The ventricular septum, however, has only muscular and membranous components. The muscular part incorporates a small component derived from the muscularised fused proximal outflow cushions, but this part cannot be distinguished from the much larger part that is incorporated within the free-standing muscular infundibular sleeve. We confirm that the tricuspid valve itself has three components, which are located inferiorly, septally, and antero-superiorly.<br/

The Early “Unnatural” History Following Surgical Repair of Ventricular Septal Defects

Introduction Surgical outcomes for simple ventricular septaldefects (VSD) have been excellent in the past three decades. Forthis project, the timing of resolution of left-sided dilation and mitralregurgitation (MR) following VSD repair was assessed. Methods Echocardiographic data surrounding surgery of 42 consecutivechildren who underwent surgical patch repair of a VSD werereviewed. The echocardiograms were reviewed up to a mean of 12months post-operatively (range 9 - 14 months). Quantitative dataindexed to body surface area including left atrial (LA) volume, mitralvalve annulus diameter, and left ventricular end-diastolic dimension(LVEDD) was analyzed. Results The majority of our pre-surgical cohort had only trace(44%) or no MR (31%), with a small proportion having mild (16%)or moderate MR (9%). No patients had moderate or greater MR followingrepair at follow-up. The median mitral valve annular Z-scorewas 1.8 (SD 1.6; range: -1.2 to 4.1) pre-operatively, improving to a 0.6(range: -1.7 to 2.4; p &lt; 0.001) at follow-up. LA dilation was present in70% of patients, with a median LA volume Z-score of 1.1 (range: -2.6to 15.5), decreasing to 13% median Z-score -1.2 (range: -3.5 to 2.9; p&lt; 0.001) at follow-up. LV dilation was present in 81% of pre-operativepatients with a median LVEDD Z-score of 3.0 (range: -2.0 to 7.9).There was significant improvement in qualitative assessment of LVenlargement (25%) with a median LVEDD Z-score of 0.5 (range:-2.1 to 2.9; p &lt; 0.001) at follow-up. Discharge echocardiogram wasperformed at a mean of 5.7 days (range: 3 - 12 days) following surgery. Conclusions Normalization of LA, mitral valve annulus, and LV sizeoccurred within the first three months in the majority of patients, withsignificant changes occurring within the first post-operative weekfollowing surgical repair for VSD

Assessing the Criteria for Definition of Perimembranous Ventricular Septal Defects in Light of the Search for Consensus

Background: Discussions continue as to whether ventricular septal defects are best categorized according to their right ventricular geography or their borders. This is especially true when considering the perimembranous defect. Our aim, therefore, was to establish the phenotypic feature of the perimembranous defect, and to establish the ease of distinguishing its geographical variants. Methods and results: We assessed unrepaired isolated perimembranous ventricular defects from six historic archives, subcategorizing them using the ICD-11 coding system. We identified 365 defects, of which 94 (26%) were deemed to open centrally, 168 (46%) to open to the outlet, and 84 (23%) to the inlet of the right ventricle, with 19 (5%) being confluent. In all hearts, the unifying phenotypic feature was fibrous continuity between the leaflets of the mitral and tricuspid valves. This was often directly between the valves, but in all instances incorporated continuity through the atrioventricular portion of the membranous septum. In contrast, we observed fibrous continuity between the leaflets of the tricuspid and aortic valves in only 298 (82%) of the specimens. When found, discontinuity most commonly was seen in the outlet and central defects. There were no discrepancies between evaluators in distinguishing the borders, but there was occasional disagreement in determining the right ventricular geography of the defect. Conclusions: The unifying feature of perimembranous defects, rather than being aortic-to-tricuspid valvar fibrous continuity, is fibrous continuity between the leaflets of the atrioventricular valves. While right ventricular geography is important in classification, it is the borders which are more objectively defined

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

The Fate of the Outflow Tract Septal Complex in Relation to the Classification of Ventricular Septal Defects

It is now established that the entity often described as an &#8220;aortopulmonary septal complex&#8222; is better considered as an &#8220;outflow tract septal complex&#8222;. This change is crucial for appropriate understanding of not only malformations of the outflow tract, but also ventricular septal defects. Thus, the embryonic outflow tract, as it develops, is separated into its two components by fusion of a protrusion from the dorsal wall of the aortic sac with the distal end of the outflow cushions. The key point with regard to morphogenesis is that, with ongoing development, these structures lose their septal integrity, although they can still be identified as septal structures when the ventricular septum itself is deficient. In the normal postnatal heart, however, the aortic and pulmonary components have their own walls throughout the length of the outflow tracts. All of this is of clinical significance, since some current concepts of categorisation of the ventricular septal defects are based on the existence in the normal heart of a &#8220;conal septum&#8222;, along with a &#8220;septum of the atrioventricular canal&#8222;. In this review, we show how analysis of postnatal hearts reveals the definitive ventricular septum to possess only muscular and fibrous components in the absence of either discrete outflow or inlet components. We also show that this information regarding development, in turn, is of major significance in determining whether categorisation of ventricular septal defects is best approached, in the first instance, on the basis of the borders of the defects or the fashion in which they open to the right ventricle