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.
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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.
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- 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
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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
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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
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Although pulmonary arterial hypertension (PAH) leads to right ventricle (RV) hypertrophy and structural remodeling, the relative contributions of changes in myocardial geometric and mechanical properties to systolic and diastolic chamber dysfunction and their time courses remain unknown. Using measurements of RV hemodynamic and morphological changes over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we discriminated the contributions of RV geometric remodeling and alterations of myocardial material properties to changes in systolic and diastolic chamber function. Significant and rapid RV hypertrophic wall thickening was sufficient to stabilize ejection fraction in response to increased pulmonary arterial pressure by week 4 without significant changes in systolic myofilament activation. After week 4, RV end-diastolic pressure increased significantly with no corresponding changes in end-diastolic volume. Significant RV diastolic chamber stiffening by week 5 was not explained by RV hypertrophy. Instead, model analysis showed that the increases in RV end-diastolic chamber stiffness were entirely attributable to increased resting myocardial material stiffness that was not associated with significant myocardial fibrosis or changes in myocardial collagen content or type. These findings suggest that whereas systolic volume in this model of RV pressure overload is stabilized by early RV hypertrophy, diastolic dilation is prevented by subsequent resting myocardial stiffening. NEW & NOTEWORTHY Using a novel combination of hemodynamic and morphological measurements over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we found that compensated systolic function was almost entirely explained by RV hypertrophy, but subsequently altered RV end-diastolic mechanics were primarily explained by passive myocardial stiffening that was not associated with significant collagen extracellular matrix accumulation.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/https://doi.org/10.1007/s11340-020-00664-8
