Resolving the True Ventricular Mural Architecture

Figures

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  Figure 1. The scanning electron micrograph, taken from a sub-volume of the ventricular wall, shows how the individual cardiomyocytes are aggregated together by the endomysial component of the fibrous matrix into units that are separated by perimysial clefts containing loose connective tissue. There is, however, no uniformity in the thickness of the aggregated units, which can be seen to be heterogeneous and interconnected branching entities.

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  Figure 2. The drawing shows the angles used to define the three-dimensional orientation of the aggregated cardiomyocytes. Plane A is the circumferential-longitudinal plane parallel to the epicardium, while plane B is the radial-longitudinal plane. Plane B is parallel to the left ventricular long axis, and orthogonal to plane A. The third plane, C, is the circumferential-radial plane, which is orthogonal to planes A and B. The helical angle α is the angle between the chain of aggregated cardiomyocytes (yellow rod) and plane C. The transmural angle β is the angle between the chain and plane A. The E3 angle γ is measured as the angle between the aggregate and the circumferential-longitudinal plane. The unit of aggregated cardiomyocytes, depicted as a flat box, is a gross oversimplification of the true three-dimensional arrangement.

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  Figure 3. The dissection shown in the (left hand) panel was made by removing or ‘peeling’ the epicardial covering of the ventricular cone. It shows the obvious “grain” produced by the aggregation of the cardiomyocytes into chains. Note that the superficial cardiomyocytes are shared between the ventricles, with no traceable division. The left ventricular chains show a marked angle relative to the ventricular long axis. The image shown in the (right hand) panel demonstrates that the cardiomyocytes in the left ventricular mid-wall are aggregated in circumferential fashion.

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  Figure 4. The morphological substrate for the enigmatic ‘echogenic bright line’ was resolved by multi-modality imaging. (A) The echogenic bright line viewed in the short axis derived from apical long axis images; Structure tensor analysis of diffusion tensor magnetic resonance imaging (B) and micro-computed tomography (C) data sets, white pixels indicate areas of circumferentially running myocytes; (D) This morphological arrangement it not easily appreciated in dissected specimens. Modified from Agger et al., 2016 [45].

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  Figure 5. Panel (A) shows a histological section of the right ventricular wall of the sheep heart stained with hemotoxylin and eosin, revealing the heterogeneous mural architecture. The helical angle of the chains of cardiomyocytes aggregated together within the right ventricular walls is shown in panel (B), which is a tractograph generated from different zones of the walls. The color coding of the tractography does not represent any anatomical or physiological property. It serves only as a visual aid enabling the reader to distinguish between the tracks, and to visualize the mean orientation of cardiomyocytes within them. Modified from Agger et al., 2015 [48].

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  Figure 6. The drawings show the essence of mural antagonism. During contraction, tangentially arranged chains of cardiomyocytes are subjected to a progressive decrease in hemodynamic afterload. Because of this, their force magnitude decreases over the cardiac cycle, thus producing a constrictive force component which is unloading in nature. In contrast, during cardiac contraction, those chains of cardiomyocytes aligned in transmural fashion are subjected to a progressive increase in intrinsic afterload. Their force magnitude, therefore, increases over the cardiac cycle, thus producing an antagonistic and dilatory force component, which is auxotonic in nature. Modified from Lunkenheimer et al., 2018 [16].

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  Figure 7. The figure shows the virtual histology of the aggregated units of cardiomyocytes as revealed using micro-computed tomography. Panel (A) shows a long axis transmural image obtained from the basal region of the posterior wall of the left ventricle. The arrangement of the cardiomyocytes in the yellow dashed box is then shown in panel (B), which is an histological section stained with hematoxylin and eosin, and panels (C,D), which are micro-CT images. It is possible, in panel (D), to recognize the individual cardiomyocytes, shown in the yellow circles, the branches between adjacent aggregated units, shown by the asterisks, and the cleavage planes (CP) between the units. The scale bars in panels B, C and D represent 100 µm. Panel (E) shows volume rendering of a subendocardial block of rabbit ventricular wall, showing the three-dimensional morphology of multiple aggregates. In Panel (F), a solitary aggregated unit of cardiomyocytes, shown in orange, has been reconstructed subsequent to resolution of the contained individual chains of cardiomyocytes. The illustrations are modified from Stephenson et al., 2016 [18]. Our work is now continuing so as to characterize the morphology of the…