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Myocardial Mesostructure and Mesofunction

Research output: Contribution to journalArticlepeer-review

Alexander J. Wilson, Gregory B. Sands, Ian J. LeGrice, Alistair A. Young, Daniel B. Ennis

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2
Early online date11 Jul 2022
Accepted/In press23 May 2022
E-pub ahead of print11 Jul 2022
Published1 Aug 2022

Bibliographical note

Funding Information: systolic confirmation. This is supported by the E2A frequency distributions in diastole Funding Information: This work was supported, in part, by funding from the American Heart Association (AHA 19IPLOI34760294 to DBE), and the National Institutes of Health, National Heart, Lung, and Blood Institute (NIH/NHLBI R01-HL131823 to DBE, R01-HL152256 to DBE). Publisher Copyright: © 2022 American Physiological Society. All rights reserved.

King's Authors


The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the human heart. The characteristic transmural change in cardiomyocyte orientation underlies base-to-apex shortening, circumferential shortening, and left ventricular torsion during contraction. Individual cardiomyocytes shorten approximately 15% and increase in diameter approximately 8%. Remarkably, however, the left ventricular wall thickens by up to 30-40%. To accommodate this, the myocardium must undergo significant structural rearrangement during contraction. At the mesoscale, collections of cardiomyocytes are organized into sheetlets, and sheetlet shear is the fundamental mechanism of rearrangement that produces wall thickening. Herein we review the histological and physiological studies of myocardial mesostructure that have established the sheetlet shear model of wall thickening. Recent developments in tissue clearing techniques allow for imaging of whole hearts at the cellular scale, while magnetic resonance imaging (MRI) and computed tomography (CT) can image the myocardium at the mesoscale (100µm to 1mm) to resolve cardiomyocyte orientation and organization. Through histology, cardiac diffusion tensor imaging (DTI) and other modalities, mesostructural sheetlets have been confirmed in both animal and human hearts. Recent in vivo cardiac DTI methods have measured reorientation of sheetlets during the cardiac cycle. We also examine the role of pathological cardiac remodeling on sheetlet organization and reorientation, and the impact this has on ventricular function and dysfunction. We also review the unresolved mesostructural questions and challenges that may direct future work in the field.

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