A quantitative structural and morphometric analysis of the Purkinje network and the Purkinje–myocardial junctions in pig hearts

Abstract

The morpho-functional properties of the distal section of the cardiac Purkinje network (PN) and the Purkinje-myocardial junctions (PMJs) are fundamental to understanding the sequence of electrical activation in the heart. The overall structure of the system has already been described, and several computational models have been developed to gain insight into its involvement in cardiac arrhythmias or its interaction with implantable devices, such as pacemakers. However, anatomical descriptions of the PN in the literature have not enabled enough improvements in the accuracy of anatomical-based electrophysiological simulations of the PN in 3D hearts models. In this work, we study the global distribution and morphological properties of the PN, with special emphasis on the cellular and architectural characterization of its intramural branching structure, mesh-like sub-endocardial network, and the PMJs in adult pig hearts by both histopathological and morphometric evaluation. We have defined three main patterns of PMJ: contact through cell bodies, contact through cell prolongations either thick or piliform, and contact through transitional cells. Moreover, from hundreds of micrographs, we quantified the density of PMJs and provided data for the basal/medial/apical regions, anterior/posterior/septal/lateral regions and myocardial/sub-endocardial distribution. Morphometric variables, such as Purkinje cell density and thickness of the bundles, were also analyzed. After combining the results of these parameters, a different septoanterior distribution in the Purkinje cell density was observed towards the cardiac apex, which is associated with a progressive thinning of the conduction bundles and the posterolateral ascension of intramyocardial terminal scattered fibers. The study of the PMJs revealed a decreasing trend towards the base that may anatomically explain the early apical activation. The anterolateral region contains the greatest number of contacts, followed by the anterior and septal regions. This supports the hypothesis that thin distal Purkinje bundles create a junction-rich network that may be responsible for the quick apical depolarization. The PN then ascends laterally and spreads through the anterior and medial walls up to the base. We have established the first morphometric study of the Purkinje system, and provided quantitative and objective data that facilitate its incorporation into the development of models beyond gross and variable pathological descriptions, and which, after further studies, could be useful in the characterization of pathological processes or therapeutic procedures.

Crista Supraventricularis Purkinje Network and Its Relation to Intraseptal Purkinje Network

“…According to Abramson and Margolin (), Wahlin described in 1928 an intramyocardial plexus in the interventricular septum of a calf's heart. This was subsequently confirmed by several authors in different animals [bovine (Cardwell and Abramson, ); sheep, bovine, dog and pig (Abramson and Margolin, ); pig (Garcia‐Bustos et al, ); ruminants (Meyling and Ter Borg, ); sheep (Ryu et al, ); bovine (De Almeida et al, )]. Others did not find it [in bovine (Truex et al, ); in sheep (Chiodi and Bortolami, )) or just did not mention it (in bovine (Oosthoek et al, ); in sheep (Ansari et al, )].…”

Automatic estimation of Purkinje‐Myocardial junction hot‐spots from noisy endocardial samples: A simulation study

“…The latter approach has been performed with different mathematical techniques that range from simple fractal trees to complex and dense network structures based on L‐systems . Another method is based on segmentation of the proximal section of the PKN from ex vivo biological, but PMJs cannot be obtained, except at a few specific locations . However, all those strategies are valid for mechanistic studies and do not allow to generate patient‐specific activation sequences or ECGs, such as those presented in our work.…”

“…10 Another method is based on segmentation of the proximal section of the PKN from ex vivo biological, 12,13,35,36 but PMJs cannot be obtained, except at a few specific locations. 15 However, all those strategies are valid for mechanistic studies and do not allow to generate patient-specific activation sequences or ECGs, such as those presented in our work. EAM data have been used in different ways to estimate the PKN to subsequently perform simulations of cardiac electrophysiology.…”

“…Therefore, the activation of the ventricular tissue is dictated by the Purkinje system morphology and the relative time of PMJ activation. The PKN has been described macroscopically from photographs, microCT imaging, and microscopically from histological samples, in different species such as rabbit and pig . Even though there have been comprehensive studies of the PKN, there are only few studies that aim at quantifying the location and density of PMJs, and they are usually performed in animals .…”

“…15 Even though there have been comprehensive studies of the PKN, 11 there are only few studies that aim at quantifying the location and density of PMJs, and they are usually performed in animals. 15 The PKN is necessary in a computer model of the heart, to simulate not only the normal activation but also a number of pathologies such as left bundle branch block or sustained ventricular tachycardia macro-re-entries [16][17][18][19] in which the PKN is retrogradely activated and used to transport the electrical impulse. 20 Despite the interaction of the PKN with disease, 16,21 therapies, 20,22 and drugs, 5 most modellers have opted for paying little attention to it and instead have indirectly considered its function by altering the model's endocardial properties.…”