Perivascular adipose tissue (PVAT) is increasingly recognized as an essential layer of the functional vasculature, being responsible for producing vasoactive substances and assisting arterial stress relaxation. Here, we test the hypothesis that PVAT reduces aortic stiffness. Our model was the thoracic aorta of the male Sprague–Dawley rat. Uniaxial mechanical tests for three groups of tissue were performed: aorta with PVAT attached (+PVAT) or removed (−PVAT), and isolated PVAT (PVAT only). The output of the mechanical test is reported in the form of a Cauchy stress-stretch curve. This work presents a novel, physiologically relevant approach to measure mechanical stiffness ex vivo in isolated PVAT. Low-stress stiffness ( E 0 ), high-stress stiffness ( E 1 ), and the stress corresponding to a stretch of 1.2 (σ 1.2 ) were measured as metrics of distensibility. The low-stress stiffness was largest in the −PVAT samples and smallest in PVAT only samples. Both the high-stress stiffness and the stress at 1.2 stretch were significantly higher in −PVAT samples when compared with +PVAT samples. Taken together, these results suggest that −PVAT samples are stiffer (less distensible) both at low stress (not significant) as well as at high stress (significant) when compared with +PVAT samples. These conclusions are supported by the results of the continuum mechanics material model that we also used to interpret the same experimental data. Thus, tissue stiffness is significantly lower when considering PVAT as part of the aortic wall. As such, PVAT should be considered as a target for improving vascular function in diseases with elevated aortic stiffness, including hypertension. NEW & NOTEWORTHY We introduce a novel and physiologically relevant way of measuring perivascular adipose tissue (PVAT) mechanical stiffness which shows that PVAT’s low, yet measurable, stiffness is linearly correlated with the amount of collagen fibers present within the tissue. Including PVAT in the measurement of the aortic wall’s mechanical behavior is important, and it significantly affects the resulting metrics by decreasing aortic stiffness.
more »
« less
Left Ventricular Geometry, Tissue Composition, and Residual Stress in High Fat Diet Dahl-Salt Sensitive Rats.
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.
more »
« less
- Award ID(s):
- 1933768
- NSF-PAR ID:
- 10282172
- Date Published:
- Journal Name:
- Experimental mechanics
- Volume:
- 61
- ISSN:
- 0014-4851
- Page Range / eLocation ID:
- 191–201
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Baek, Seungik (Ed.)more » « less
Introduction: The right ventricle (RV) mechanical property is an important determinant of its function. However, compared to its elasticity, RV viscoelasticity is much less studied, and it remains unclear how pulmonary hypertension (PH) alters RV viscoelasticity. Our goal was to characterize the changes in RV free wall (RVFW) anisotropic viscoelastic properties with PH development and at varied heart rates.Methods: PH was induced in rats by monocrotaline treatment, and the RV function was quantified by echocardiography. After euthanasia, equibiaxial stress relaxation tests were performed on RVFWs from healthy and PH rats at various strain-rates and strain levels, which recapitulate physiological deformations at varied heart rates (at rest and under acute stress) and diastole phases (at early and late filling), respectively.Results and Discussion: We observed that PH increased RVFW viscoelasticity in both longitudinal (outflow tract) and circumferential directions. The tissue anisotropy was pronounced for the diseased RVs, not healthy RVs. We also examined the relative change of viscosity to elasticity by the damping capacity (ratio of dissipated energy to total energy), and we found that PH decreased RVFW damping capacity in both directions. The RV viscoelasticity was also differently altered from resting to acute stress conditions between the groups—the damping capacity was decreased only in the circumferential direction for healthy RVs, but it was reduced in both directions for diseased RVs. Lastly, we found some correlations between the damping capacity and RV function indices and there was no correlation between elasticity or viscosity and RV function. Thus, the RV damping capacity may be a better indicator of RV function than elasticity or viscosity alone. These novel findings on RV dynamic mechanical properties offer deeper insights into the role of RV biomechanics in the adaptation of RV to chronic pressure overload and acute stress. -
more » « less
Background Clinical management of boys with Duchenne muscular dystrophy (DMD) relies on in‐depth understanding of cardiac involvement, but right ventricular (RV) structural and functional remodeling remains understudied.
Purpose To evaluate several analysis methods and identify the most reliable one to measure RV pre‐ and postcontrast T1 (RV‐T1) and to characterize myocardial remodeling in the RV of boys with DMD.
Study Type Prospective.
Population Boys with DMD (
N = 27) and age‐/sex‐matched healthy controls (N = 17) from two sites.Field Strength/Sequence 3.0 T using balanced steady state free precession, motion‐corrected phase sensitive inversion recovery and modified Look‐Locker inversion recovery sequences.
Assessment Biventricular mass (Mi), end‐diastolic volume (EDVi) and ejection fraction (EF) assessment, tricuspid annular excursion (TAE), late gadolinium enhancement (LGE), pre‐ and postcontrast myocardial T1 maps. The RV‐T1 reliability was assessed by three observers in four different RV regions of interest (ROI) using intraclass correlation (ICC).
Statistical Tests The Wilcoxon rank sum test was used to compare RV‐T1 differences between DMD boys with negative LGE(−) or positive LGE(+) and healthy controls. Additionally, correlation of precontrast RV‐T1 with functional measures was performed. A
P ‐value <0.05 was considered statistically significant.Results A 1‐pixel thick RV circumferential ROI proved most reliable (ICC > 0.91) for assessing RV‐T1. Precontrast RV‐T1 was significantly higher in boys with DMD compared to controls. Both LGE(−) and LGE(+) boys had significantly elevated precontrast RV‐T1 compared to controls (1543 [1489–1597] msec and 1550 [1402–1699] msec vs. 1436 [1399–1473] msec, respectively). Compared to healthy controls, boys with DMD had preserved RVEF (51.8 [9.9]% vs. 54.2 [7.2]%,
P = 0.31) and significantly reduced RVMi (29.8 [9.7] g vs. 48.0 [15.7] g), RVEDVi (69.8 [29.7] mL/m2vs. 89.1 [21.9] mL/m2), and TAE (22.0 [3.2] cm vs. 26.0 [4.7] cm). Significant correlations were found between precontrast RV‐T1 and RVEF (β = −0.48%/msec) and between LV‐T1 and LVEF (β = −0.51%/msec).Data Conclusion Precontrast RV‐T1 is elevated in boys with DMD compared to healthy controls and is negatively correlated with RVEF.
Level of Evidence 1
Technical Efficacy Stage 2
-
more » « less
ABSTRACT Overuse‐induced tendinopathy is highly prevalent in the general population. Percutaneous fenestration, or dry needling, techniques have been increasing in popularity, but despite their current use, there are no controlled laboratory studies to provide fundamental support for this practice. The objective of this study was to establish a model for percutaneous needling of the rat supraspinatus tendon using ultrasound guidance and to evaluate the biological response of needling healthy tendon. A total of 44 male Sprague–Dawley rats (477 ± 39 g) were used to evaluate the effect of dry needling on healthy supraspinatus tendon properties. Ten rats were reserved as un‐needled control animals, and the remaining animals underwent either mild or moderate bilateral needling protocols and were sacrificed at 1 or 6 weeks post‐needling (
n = 8–10/group). Color Doppler ultrasound imaging was performed to analyze blood flow within the tendon. Histological and immunohistochemical analyses were used to determine cellular, inflammatory, and extracellular matrix properties of the tissue. Finally, quasi‐static tensile mechanical analysis was performed to obtain viscoelastic, structural, and material properties to evaluate the tendon healing outcome. Data were tested for normality, and then two‐way analysis of variance tests were performed followed by post hoc tests for multiple comparisons. Both the mild and moderate needling groups caused a transient healing response at early time points as shown by a statistically significant (p < 0.05) reduction in mechanical properties, and increase in blood flow, inflammation, and production of collagen III and glycosaminoglycans as compared to the control. Furthermore, mild needling properties returned to or exceeded pre‐needling values at the 6‐week time point. Clinical significance: Needling the rat supraspinatus tendon is a feasible technique that causes a transient healing response followed by a return to, or improvement of, normal tendon properties, indicating potential applicability in understanding the effects of current practices utilizing dry needling of tendons in humans. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2035–2042, 2019 -
Abstract We propose a novel structure-based two-dimensional (2D) mathematical model of hypertension-induced arterial remodeling. The model is built in the framework of the constrained mixture theory and global growth approach, utilizing a recently proposed structure-based constitutive model of arterial tissue that accounts for the individual natural configurations of and stress interaction between elastin and collagen. The basic novel predictive result is that provided remodeling causes a change in the elastin/collagen mass fraction ratio, it leads to a structural reorganization of collagen that manifests as an altered fiber undulation and a change in direction of the helically oriented fibers in the tissue natural state. Results obtained from the illustrative simulations for a porcine renal artery show that when remodeling is complete the collagen reorganization might have significant effects on the initial arterial geometry and mechanical properties of the arterial tissue. The proposed model has potential to describe and advance mechanistic understanding of adaptive arterial remodeling, promote the continual refinement of mathematical models of arterial remodeling, and provide motivation for new avenues of experimental investigation.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/https://doi.org/10.1007/s11340-020-00664-8
