What is the clinical significance of ventricular mural antagonism?

Abstract

Recent morphological studies provide evidence that the ventricular walls are arranged as a 3D meshwork of aggregated cardiomyocyte chains, exhibiting marked local structural variations. In contrary to previous findings, up to two-fifths of the chains are found to have a partially transmural alignment, thus deviating from the prevailing tangential orientation. Upon contraction, they produce, in addition to a tangential force, a radial force component that counteracts ventricular constriction and aids widening of the ventricular cavity. In experimental studies, we have provided evidence for the existence of such forces, which are auxotonic in nature. This is in contrast to the tangentially aligned myocytes that produce constrictive forces, which are unloading in nature. The ventricular myocardium is, therefore, able to function in an antagonistic fashion, with the prevailing constrictive forces acting simultaneously with a dilatory force component. The ratio of constrictive to dilating force varies locally according to the specific mural architecture. Such antagonism acts according to local demands to preserve the ventricular shape, store the elastic energy that drives the fast late systolic dilation and apportion mural motion to facilitate the spiralling nature of intracavitary flow. Intracavitary pressure and flow dynamics are thus governed concurrently by ventricular constrictive and dilative force components. Antagonistic activity, however, increases deleteriously in states of cardiac disease, such as hypertrophy and fibrosis. ß-blockade at low dosage acts selectively to temper the auxotonic forces.

Myoarchitectural disarray of hypertrophic cardiomyopathy begins pre‐birth

“…This angle of intrusion has been suggested to underscore the existence of auxotonic as opposed to unloading ventricular forces (Lunkenheimer et al. ; Stephenson et al. ).…”

“…On the other hand, the angle of intrusion was more heterogeneously distributed in the mutant hearts, which agrees with a previous study on a hypertrophic murine model based on the administration of angiotensin II (Schmitt et al 2009). This angle of intrusion has been suggested to underscore the existence of auxotonic as opposed to unloading ventricular forces (Lunkenheimer et al 2018;Stephenson et al 2018). Those cardiomyocytes exhibiting a significant transmural orientation have both constrictive and dilating force components, and the ratio of those components varies locally according to the prevalence of angles of intrusion or extrusion.…”

“…It has been hypothesised that such mural antagonism serves to stabilise ventricular shape and size, to sustain late systolic dilation, to confine the amplitude of ventricular mural thickening, and to facilitate and enhance the spiralling intracavity flow (Lunkenheimer et al. ). Finally, some authors have also described the existence of myocardial ‘sheets’ or ‘sheetlets,’ thus proposing a third angle to describe the orientation of myocytes (McGill et al.…”

“…Those cardiomyocytes exhibiting a significant transmural orientation have both constrictive and dilating force components, and the ratio of those components varies locally according to the prevalence of angles of intrusion or extrusion. It has been hypothesised that such mural antagonism serves to stabilise ventricular shape and size, to sustain late systolic dilation, to confine the amplitude of ventricular mural thickening, and to facilitate and enhance the spiralling intracavity flow (Lunkenheimer et al 2018). Finally, some authors have also described the existence of myocardial 'sheets' or 'sheetlets,' thus proposing a third angle to describe the orientation of myocytes (McGill et al 2013;Agger et al 2017;Nielles-Vallespin et al 2017;Stoeck et al 2018).…”

Anatomically correct assessment of the orientation of the cardiomyocytes using diffusion tensor imaging

“…4,17,18,21,23,27,[34][35][36][37] Evidence now shows that the radial orientation of cardiomyocytes is not only a fact, [38][39][40] but is also a key physiological element for optimal cardiac performance. 28,29,41,42 This obvious lack of consensus in the literature is reflected in published results, which are impossible to compare in a meaningful fashion. If we are to reach consensus regarding the architecture of the ventricular walls, we need to agree upon what is measured, and how we define the orientations of the contained cardiomyocytes.…”