Left Ventricular Geometry, Tissue Composition, and Residual Stress in High Fat Diet Dahl-Salt Sensitive Rats

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SP ISS: EXPERIMENTAL ADVANCES IN CARDIOVASCULAR BIOMECHANICS

Left Ventricular Geometry, Tissue Composition, and Residual Stress in High Fat Diet Dahl-Salt Sensitive Rats M.R. Grobbel 1 & L.C. Lee 1 & S.W. Watts 2 & G.D. Fink 2 & S. Roccabianca 1 Received: 3 February 2020 / Accepted: 2 September 2020 # Society for Experimental Mechanics 2020

Abstract Background Hypertension drives myocardial remodeling, leading to changes in structure, composition and mechanical behavior, including residual stress, which are linked to heart disease progression in a gender-specific manner. Emerging therapies are also targeting constituent-specific pathological features. All previous studies, however, have characterized remodeling in the intact tissue, rather than isolated tissue constituents, and did not include sex as a biological variable. Objective In this study we first identified the contribution of collagen fiber network and myocytes to the myocardial residual stress/strain in Dahl-Salt sensitive rats fed with high fat diet. Then, we quantified the effect of hypertension on the remodeling of the left ventricle (LV), as well as the existence of sex-specific remodeling features. Methods We performed mechanical tests (opening angle, ring-test) and histological analysis on isolated constituents and intact tissue of the LV. Based on the measurements from the tests, we performed a stress analysis to evaluate the residual stress distribution. Statistical analysis was performed to identify the effects of constituent isolation, elevated blood pressure, and sex of the animal on the experimental measurements and modeling results. Results Hypertension leads to reduced residual stress/strain in the intact tissue, isolated collagen fibers, and isolated myocytes in male and female rats. Collagen remains the largest contributor to myocardial residual stress in both normotensive and hypertensive animals. We identified sex-differences in both hypertensive and normotensive animals. Conclusions We observed both constituent- and sex-specific remodeling features in the LV of an animal model of hypertension. Keywords Left ventricular mechanics . Residual stress . Cardiac mechanics . Extracellular matrix

Introduction Cardiovascular disease, specifically hypertension, has been shown to alter the left ventricle (LV) tissue structure, composition, and ultimately mechanical behavior [1, 2]. Exposed to high afterload over a prolonged period of time, pathological features such as myocyte hypertrophy, fibrosis, and elevated resting tension of the myocytes are developed in the LV, which in turn produce concentric hypertrophy globally [3, 4]. These microstructural pathological changes can also affect the residual stress/strain distribution in the LV as shown in * S. Roccabianca [email protected] 1

Mechanical Engineering Department, Michigan State University, East Lansing, MI, USA

2

Pharmacology & Toxicology Department, Michigan State University, East Lansing, MI, USA

previous studies, which reported a larger opening angle (OA) in the intact hearts su