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 output of both experimental measures and modeling results. RESULTS: Hypertension leads to reduced residual stress/strain 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.