Elevated Strain and Structural Disarray Occur at the Right Ventricular Apex

Hariharan, Venkatesh; Provost, Jean; Shah, Shailee; Konofagou, Elisa E.; Huang, Hayden

doi:10.1007/s13239-011-0081-3

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…36 The right ventricular apex, an area preferentially affected in ARVC, exhibits heterogeneous fiber orientation and elevated incremental strains, potentially creating a mechanically weak spot in the heart. 37 Finally, electron microscopy studies of patient myocardial samples have reported decreased numbers of desmosomes and apparent clefts or widening of various components within the intercalated disks. 38 All of these observations suggest that mechanical stress plays an important role in disease progression and sudden death.…”

Section: More Than a Disease Of Abnormal Cell-cell Adhesionmentioning

confidence: 99%

Remodeling of Cell-Cell Junctions in Arrhythmogenic Cardiomyopathy

Asimaki

Saffitz

2014

Cell Communication & Adhesion

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Arrhythmogenic cardiomyopathy (AC) is a primary myocardial disorder characterized by a high incidence of ventricular arrhythmias often preceding the onset of ventricular remodeling and dysfunction. Approximately 50% of patients diagnosed with AC have one or more mutations in genes encoding desmosomal proteins, although non-desmosomal genes have also been associated with the disease. Increasing evidence implicates remodeling of intercalated disk proteins reflecting abnormal responses to mechanical load and aberrant cell signaling pathways in the pathogenesis of AC. This review summarizes recent advances in understanding disease mechanisms in AC that have come from studies of human myocardium and experimental models.

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Section: More Than a Disease Of Abnormal Cell-cell Adhesionmentioning

confidence: 99%

Remodeling of Cell-Cell Junctions in Arrhythmogenic Cardiomyopathy

Asimaki

Saffitz

2014

Cell Communication & Adhesion

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“…Arrhythmogenic right ventricular cardiomyopathy/dyplasia (ARVC/D) preferentially affects the right ventricular epicardium between the conus and apex, a region called “the triangle of dysplasia”. The RV wall bears higher strains for longer periods of time, has elevated changes in strain over short periods of time, and near the apex is subject to heterogeneity in strain distribution over a small volume (Hariharan et al, ). The marked disarray at the RV apex signifies abrupt changes in myocyte orientation and loss of end‐to‐end coupling.…”

Section: The Morphology Of the Right Ventriclementioning

confidence: 99%

The clinical anatomy of the right ventricle

Mureşian

2014

Clinical Anatomy

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Because the systemic and pulmonary circulations are arranged in series, the right and left ventricles of the human heart have similar stroke volumes (with only minute beat-to-beat changes). Besides propelling the same volume of blood through the corresponding circulations, the two ventricles also share common structures such as the pericardium, the interventricular septum and the coronary arteries and veins-all of which complete the dynamic and integrated picture of the human heart. However, there are marked differences between the left and right ventricles as each is adapted to separate and dissimilar vascular beds, including particular reactivity to stress, hormones, and drugs. Of the two, the right ventricle (RV) has so far been either more difficult to approach from the diagnostic point of view or even overlooked, while the left ventricle (LV) has been considered the main pump, and diagnostic and therapeutic measures have been considered to apply equally to the LV and RV. This review article presents an update, portraying the RV from the clinical anatomical point of view, and endeavors to underscore the main particulars of the RV with clinical and surgical applications.

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“…20 In the splayed ‘starburst’ geometry, fibers diverge or converge, as in papillary muscle insertions in the endocardium and in the right ventricular apex, one of the corners of the ‘triangle of dysplasia’ in arrhythmogenic right ventricular cardiomyopathy. 26 In our analysis, we found that the tissue electrophysiology, in terms of AP durations and regional longitudinal and transverse conduction velocities, was similar among all of the anisotropic geometries, yielding however strikingly different and novel patterns of propagating AP waves. As discussed below, this alteration of the pattern of AP propagation, in addition to enhancing our understanding of the variability in normal organization, can be suggestive of pathological states.…”

Section: Discussionmentioning

confidence: 60%

“…It needs to be pointed out, however, that DTMRI data is 3D in nature while our current methodology is 2D, which makes translating our model of tissue patterning to this application difficult without further advancements in the technology. The precision of our method also increases the diversity of possible patterns at the cellular level, which could provide insight as to why ventricular tachyarrhythmias arise in the ventricular septum in hypertrophic cardiomyopathy 23,33 or in the right ventricular apex in arrhythmogenic right ventricular cardiomyopathy, 26 where there exist sharp direction changes and splaying of fibers. Furthermore, clinical readouts such as DTMRI imaging may be used in the future to develop personalized, computational simulations of a patient's heart and their possible risk for arrhythmias.…”

Section: Discussionmentioning

confidence: 99%

Precisely parameterized experimental and computational models of tissue organization

Molitoris

Paliwal

Sekar

et al. 2016

Integrative Biology

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Patterns of cellular organization in diverse tissues frequently display a complex geometry and topology tightly related to the tissue function. Progressive disorganization of tissue morphology can lead to pathologic remodeling, necessitating the development of experimental and theoretical methods of analysis of the tolerance of normal tissue function to structural alterations. A systematic way to investigate the relationship of diverse cell organization to tissue function is to engineer two-dimensional cell monolayers replicating key aspects of the in vivo tissue architecture. However, it is still not clear how this can be accomplished on a tissue level scale in a parameterized fashion, allowing for a mathematically precise definition of the model tissue organization and properties down to a cellular scale with a parameter dependent gradual change in model tissue organization. Here, we describe and use a method of designing precisely parameterized, geometrically complex patterns that are then used to control cell alignment and communication of model tissues. We demonstrate direct application of this method to guiding the growth of cardiac cell cultures and developing mathematical models of cell function that correspond to the underlying experimental patterns. Several anisotropic patterned cultures spanning a broad range of multicellular organization, mimicking the cardiac tissue organization of different regions of the heart, were found to be similar to each other and to isotropic cell monolayers in terms of local cell–cell interactions, reflected in similar confluency, morphology and connexin-43 expression. However, in agreement with the model predictions, different anisotropic patterns of cell organization, paralleling in vivo alterations of cardiac tissue morphology, resulted in variable and novel functional responses with important implications for the initiation and maintenance of cardiac arrhythmias. We conclude that variations of tissue geometry and topology can dramatically affect cardiac tissue function even if the constituent cells are themselves similar, and that the proposed method can provide a general strategy to experimentally and computationally investigate when such variation can lead to impaired tissue function.

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Elevated Strain and Structural Disarray Occur at the Right Ventricular Apex

Cited by 4 publications

References 21 publications

Remodeling of Cell-Cell Junctions in Arrhythmogenic Cardiomyopathy

Remodeling of Cell-Cell Junctions in Arrhythmogenic Cardiomyopathy

The clinical anatomy of the right ventricle

Precisely parameterized experimental and computational models of tissue organization

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