Title: Transmural Remodeling of Cardiac Microstructure in Aged Spontaneously Hypertensive Rats by Diffusion Tensor MRI

Abstract

The long-standing high blood pressure (also known as hypertension) overworks the heart. Microstructural remodeling is a key factor of hypertensive heart disease progression. Diffusion tensor magnetic resonance imaging (DT-MRI) is a powerful tool for the rapid noninvasive nondestructive delineation of the cardiomyocyte organization. The spontaneously hypertensive rat (SHR) is a well-established model of genetic hypertension. The goal of this study was to employ high-resolution DT-MRI and the SHR animal model to assess the transmural layer-specific remodeling of myocardial microstructure associated with hypertension. Ex vivo experiments were performed on excised formalin-fixed hearts of aged SHRs (n = 4) and age-matched controls (n = 4). The DT-MRI-derived fractional anisotropy (FA), longitudinal diffusivity (λ L ), transversal diffusivity (λ T ), and mean diffusivity (MD) served as the readout parameters investigated at three transmural zones (i.e., endocardium, mesocardium, and epicardium). The helix angles (HAs) of the aggregated cardiomyocytes and the orientation of laminar sheetlets were also studied. Compared with controls, the SHRs exhibited decreased epicardial FA, while FA changes in the other two transmural regions were insignificant. No substantial differences were observed in the diffusivity parameters and the transmural course of HAs between the two groups. A consistent distribution pattern of laminar sheetletmore » orientation was not identified for either group. Our findings are in line with the known cellular microstructure from early painstaking histological studies. Biophysical explanations of the study outcomes are provided. In conclusion, our experimental findings indicate that the epicardial microstructure is more vulnerable to high blood pressure leading to more pronounced changes in this region during remodeling. DT-MRI is well-suited for elucidating these alterations. The revealed transmural nonuniformity of myocardial reorganization may shed light on the mechanisms of the microstructure-function relationship in hypertension progression. Our results provide insights into the management of patients with systemic arterial hypertension, thus prevent the progression toward heart failure. The findings of this study should be acknowledged by electromechanical models of the heart that simulate the specific cardiac pathology.« less

Authors:

Giannakidis, Archontis ^[1]; Gullberg, Grant T. ^[2]

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+ Show Author Affiliations

1. Nottingam Trent Univ. (United Kingdom); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Imperial College, London (United Kingdom)
2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, San Francisco, CA (United States)

Publication Date:

Tue Mar 31 00:00:00 EDT 2020

Research Org.:

Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)

OSTI Identifier:

1619156

Grant/Contract Number:  

AC02-05CH11231; R01 EB007219

Resource Type:

Accepted Manuscript

Journal Name:

Frontiers in Physiology

Additional Journal Information:

Journal Volume: 11; Journal ID: ISSN 1664-042X

Publisher:

Frontiers

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES; myocardium; microstructure; remodeling; left ventricle; diffusion tensor MRI; hypertension