scholarly journals The Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties: A Pilot Study

2022 ◽  
Vol 8 ◽  
Author(s):  
Danial Sharifi Kia ◽  
Yuanjun Shen ◽  
Timothy N. Bachman ◽  
Elena A. Goncharova ◽  
Kang Kim ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Healthy Aging ◽  
Pressure Overload ◽  
Biomechanical Properties ◽  
Cardiovascular Fitness ◽  
Current Evidence ◽  
Sprague Dawley ◽  
Age Related ◽  
Sprague Dawley Rats ◽  
Peak Pressures

Healthy aging has been associated with alterations in pulmonary vascular and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work, we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative transmural histological analysis were employed to study two groups of male Sprague-Dawley rats: control (11 weeks) and aging (80 weeks). Aging was associated with increases in RV peak pressures (+17%, p = 0.017), RV contractility (+52%, p = 0.004), and RV wall thickness (+38%, p = 0.001). Longitudinal realignment of RV collagen (16.4°, p = 0.013) and myofibers (14.6°, p = 0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. Aging led to increased RV myofiber stiffness (+141%, p = 0.003), in addition to a bimodal alteration in the biaxial biomechanical properties of the RV free wall, resulting in increased tissue-level stiffness in the low-strain region, while progressing into decreased stiffness at higher strains. Our results demonstrate that healthy aging may modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fibrosis, fiber reorientation, and altered mechanical properties in male Sprague-Dawley rats. Similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload. These findings may help our understanding of age-related changes in the cardiovascular fitness and response to disease.

scholarly journals Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties

2020 ◽  
Author(s):  
Danial Sharifi Kia ◽  
Yuanjun Shen ◽  
Timothy N. Bachman ◽  
Elena A. Goncharova ◽  
Kang Kim ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Healthy Aging ◽  
Pressure Overload ◽  
The Elderly ◽  
Biomechanical Properties ◽  
Current Evidence ◽  
Pulmonary Vasculature ◽  
Sprague Dawley ◽  
Age Related ◽  
Peak Pressures

AbstractHealthy aging has been associated with alterations in pulmonary vasculature and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative histological analysis were employed to study two groups of Sprague-Dawley rats: control (11 weeks) and aging (80 weeks).Aging was associated with increases in RV peak pressures (≈↑17%, p=0.017), RV contractility (≈↑52%, p= 0.004), and RV wall thickness (≈↑34%, p=0.002). Longitudinal realignment of RV collagen (16.4°, p=0.013) and myofibers (14.6°, p=0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. A bimodal alteration in biomechanical properties was noted, resulting in increased myofiber stiffness (≈↑158%, p=0.0006) and decreased effective collagen fiber stiffness (≈↓67%, p=0.031).Our results demonstrate the potential of healthy aging to modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fiber reorientation, and altered collagen/myofiber stiffness. Some similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload.

Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats

2007 ◽  
Vol 292 (6) ◽  
pp. H2737-H2744 ◽  
Author(s):  
Masahito Kajiya ◽  
Masanori Hirota ◽  
Yousuke Inai ◽  
Takahiko Kiyooka ◽  
Taro Morimoto ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Pressure Overload ◽  
Suppressive Effect ◽  
Protective Role ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Small Arteries ◽  
Sprague Dawley Rats ◽  
Endothelial Nitric Oxide ◽  
Arteriolar Vasodilation

Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline ( n = 126) to induce PH or with saline as controls ( n = 114). After 3 wk, coronary arterioles (diameter = 30–100 μm) and small arteries (diameter = 100–200 μm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of Nω-nitro-l-arginine methyl ester (l-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without l-NAME, and in the presence of SOD. The degree of suppression in vasodilation by l-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.

Abstract 13140: Right Ventricular Remodeling and Changes in Tissue Biomechanics in Healthy Aging

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Danial Sharifikia ◽  
Yuanjun Shen ◽  
Timothy Bachman ◽  
Elena Goncharova ◽  
Kang Kim ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Healthy Aging ◽  
Ventricular Remodeling ◽  
Survival Rates ◽  
Biomechanical Properties ◽  
Area Fraction ◽  
Pulmonary Vasculature ◽  
Sprague Dawley ◽  
Close Link ◽  
Systolic And Diastolic Function

Introduction: Normal aging in healthy adults has been associated with pulmonary vasculature remodeling and alterations in right ventricular (RV) systolic and diastolic function, which may lead to increased RV afterload and pulmonary hypertension (PH). Previous studies have found a close link between RV biomechanics and function. While current findings suggest a connection between aging and survival rates of PH patients, limited data exist on age-associated differences in the biomechanical properties of RV myocardium. Hypothesis: Aging results in increased RV afterload, hypertrophy, and myocardial stiffening. Methods: Two groups of control (11 weeks) and aging (80 weeks) Sprague-Dawley rats were studied via terminal invasive hemodynamic measurements (n=5/group), quantitative transmural histological analysis (n=3/group; Masson’s trichrome), biaxial mechanical testing (n=6/group) and constitutive modeling (n=6/group) for a comprehensive multi-scale study on the effects of aging on RV biomechanics. Results: Aging increased RV peak pressures by 15% (26.79±0.87 vs. 23.28±0.83 mmHg for aging vs. control; p=0.020). Increased RV wall thickness (0.89±0.06 vs. 0.66±0.04 mm for aging vs. control; p=0.010) and cardiomyocyte width (25.42±0.34 vs. 14.94±0.64 μm for aging vs. control; p<0.001) were observed in the aging group, while not showing any effects on the Fulton index. Histological analyses showed transmural realignment of RV collagen and myofibers towards the apex-to-base direction by 14.6° (p=0.017). This was accompanied by transmural loss of cardiomyocytes (cardiomyocyte area fraction: 88.4%±0.4% vs. 95.3%±0.7% for aging vs. control; p<0.001) and increased myofiber stiffness (169.9±20.6 vs. 65.8±4.7 kPa for aging vs. control; p<0.001). While aging resulted in RV fibrosis (collagen area fraction: 5.1%±0.5% vs. 3.8%±0.1% for aging vs. control; p=0.049), collagen fibers in the aging myocardium showed decreased effective intrinsic stiffness compared to young controls (23.9±3.8 vs. 73.1±15.4 MPa for aging vs. control; p=0.031). Conclusions: Healthy aging has the potential to modulate RV dysfunction via increased myofiber stiffness, fiber reorientation, loss of ventricular cardiomyocytes, RV hypertrophy and fibrosis.

scholarly journals Age-related decline in the taurine content of the skin in rodents

Amino Acids ◽  
2021 ◽  
Author(s):  
Tomohisa Yoshimura ◽  
Yuki Inokuchi ◽  
Chikako Mutou ◽  
Takanobu Sakurai ◽  
Tohru Nagahama ◽  
...  
Keyword(s):  
High Performance ◽  
Age Groups ◽  
Immunohistochemical Analysis ◽  
Sprague Dawley ◽  
Taurine Supplementation ◽  
Hairless Mice ◽  
Age Related ◽  
Sprague Dawley Rats ◽  
High Concentrations ◽  
Effects Of Aging

AbstractTaurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.

scholarly journals Effects of TRPC6 Inactivation on Glomerulosclerosis and Renal Fibrosis in Aging Rats

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 856
Author(s):  
Eun Young Kim ◽  
Stuart E. Dryer
Keyword(s):  
Renal Function ◽  
Protective Effect ◽  
Renal Fibrosis ◽  
Transient Receptor Potential ◽  
Smooth Muscle Actin ◽  
Receptor Potential ◽  
Sprague Dawley ◽  
Age Related ◽  
Sprague Dawley Rats ◽  
Transient Receptor

Canonical transient receptor potential 6 (TRPC6) channels have been implicated in familial and acquired forms of focal and segmental glomerulosclerosis (FSGS) in patients and animal models, as well as in renal fibrosis following ureteral obstruction in mice. Aging also evokes declines in renal function owing to effects on almost every renal compartment in humans and rodents. Here, we have examined the role of TRPC6 in driving inflammation and fibrosis during aging in Sprague-Dawley rats. This was assessed in rats with non-functional TRPC6 channels owing to CRISPR-Cas9 deletion of a portion of the ankyrin repeat domain required for the assembly of functional TRPC6 channels (Trpc6del/del rats). Wild-type littermates (Trpc6wt/wt rats) were used as controls. Animals were evaluated at 2 months and 12 months of age. There was no sign of kidney disease at 2 months of age, regardless of genotype. However, by 12 months of age, all rats examined showed declines in renal function associated with albuminuria, azotemia and increased urine excretion of β2–microglobulin, a marker for proximal tubule pathology. These changes were equally severe in Trpc6wt/wt and Trpc6del/del rats. We also observed age-related increases in renal cortical expression of markers of fibrosis (α-smooth muscle actin and vimentin) and inflammation (NLRP3 and pro-IL−1β), and there was no detectable protective effect of TRPC6 inactivation. Tubulointerstitial fibrosis assessed from histology also appeared equally severe in Trpc6wt/wt and Trpc6del/del rats. By contrast, glomerular pathology, blindly scored from histological sections, suggested a significant protective effect of TRPC6 inactivation, but only within the glomerular compartment.

Reduction of chronic hypoxic pulmonary hypertension in the rat by beta-aminopropionitrile

1984 ◽  
Vol 57 (6) ◽  
pp. 1760-1766 ◽  
Author(s):  
J. S. Kerr ◽  
D. J. Riley ◽  
M. M. Frank ◽  
R. L. Trelstad ◽  
H. M. Frankel
Keyword(s):  
Pulmonary Hypertension ◽  
Left Ventricle ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Main Pulmonary Artery ◽  
Hydroxyproline Content ◽  
Sprague Dawley ◽  
Hypoxic Pulmonary Hypertension ◽  
Sprague Dawley Rats ◽  
Collagen Accumulation

We administered antifibrotic agent beta-aminopropionitrile (BAPN) to rats exposed to 10% O2-90% N2 for 3 wk to prevent excess vascular collagen accumulation. Groups of Sprague-Dawley rats studied were air breathing, hypoxic, and hypoxic treated with BAPN, 150 mg/kg twice daily intraperitoneally. After the 3-wk period, we measured mean right ventricular pressure (RVP), the ratio of weight of right ventricle to left ventricle plus septum (RV/LV + S), and hydroxyproline content of the main pulmonary artery (PA) trunk. Hypoxia increased RVP from 14 to 29 mmHg; RVP was 21 mmHg in hypoxic BAPN-treated animals. Hypoxia increased the RV/LV + S ratio from 0.28 to 0.41; the ratio was 0.32 in hypoxic BAPN-treated animals. Hypoxia increased PA hydroxyproline from 20 to 239 micrograms/artery; hydroxyproline was 179 micrograms/artery in hypoxic BAPN-treated animals. Thus BAPN prevented pulmonary hypertension, right ventricular hypertrophy, and excess vascular collagen produced by hypoxia. We conclude that vascular collagen contributes to the maintenance of chronic hypoxic pulmonary hypertension.

Orally administered L-arginine does not alter right ventricular hypertrophy in chronically hypoxic rats

1994 ◽  
Vol 266 (2) ◽  
pp. R559-R563 ◽  
Author(s):  
T. C. Resta ◽  
B. R. Walker
Keyword(s):  
Right Ventricular ◽  
Pulmonary Circulation ◽  
Wistar Rats ◽  
Chronic Hypoxia ◽  
Chronic Administration ◽  
Hypoxic Exposure ◽  
Sprague Dawley ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilators ◽  
Sprague Dawley Rats

Evidence suggests that nitric oxide synthesis within the pulmonary circulation may be attenuated during chronic hypoxia in Wistar rats due to reduced L-arginine availability. In contrast, chronically hypoxic Sprague-Dawley rats exhibit normal endothelium-dependent pulmonary vasodilation. The purpose of the present study was to determine whether 1) Wistar rats demonstrate greater right ventricular (RV) hypertrophy in response to chronic hypoxia than Sprague-Dawley rats and 2) chronic administration of L-arginine would diminish this response in Wistar rats. L-Arginine had no effect on the degree of hypoxia-induced RV hypertrophy or polycythemia in either strain of rat. However, Wistar rats demonstrated greater hypoxia-induced RV hypertrophy and polycythemia compared with Sprague-Dawley rats. To determine whether chronically hypoxic Wistar rats indeed exhibit impaired endothelium-dependent pulmonary vasodilation, isolated lungs from control and chronically hypoxic Wistar rats were administered the endothelium-dependent pulmonary vasodilators A23187 or vasopressin. Vasodilatory responses to either agent were unaffected by chronic hypoxic exposure. We conclude that endothelium-dependent pulmonary vasodilation is maintained in the pulmonary circulation of chronically hypoxic Wistar and Sprague-Dawley rats.

Captopril prevents vascular and fibrotic changes but not cardiac hypertrophy in aortic-banded rats

1996 ◽  
Vol 271 (3) ◽  
pp. H906-H913 ◽  
Author(s):  
C. P. Regan ◽  
P. G. Anderson ◽  
S. P. Bishop ◽  
K. H. Berecek
Keyword(s):  
Cardiac Hypertrophy ◽  
Coronary Vessels ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Vessel Morphology ◽  
Sprague Dawley Rats ◽  
Quantitative Image

To determine the role of the renin-angiotensin system (RAS) on cardiovascular remodeling in a pressure overload model of cardiac hypertrophy, a subdiaphragmatic aortic band was placed in adult male, Sprague-Dawley rats. Rats were left untreated (AB) or given captopril (Cap, 400 mg/l) (AB-Cap). Sham-operated controls were either left untreated (S) or given Cap (S-Cap). After 4 wk, rats were catheterized, and carotid and femoral mean arterial pressures (CMAP and FMAP in mmHg, respectively) were recorded. Hearts were isolated, and minimal coronary resistance (MCR) was determined. Hearts were then perfusion fixed, total and regional heart weights were recorded, and sections were processed for vessel morphology. Changes in coronary artery medical thickness and perivascular fibrosis were assessed by quantitative image analysis. CMAP was significantly higher in AB and AB-Cap than S or S-Cap rats (P < 0.05). There was no difference in FMAP in AB vs. S rats, but AB-Cap and S-Cap had lower FMAP values than S rats. Total heart weight and left ventricular weight-to-body weight ratios were increased in AB and AB-Cap rats compared with S and S-Cap rats (P < 0.05). MCR of AB was greater than S and S-Cap rats. MCR of AB-Cap rats was significantly greater than S and S-Cap rats but was significantly less than AB rats. In coronary vessels, medial thickness was greatest in AB, whereas there was no difference among AB-Cap, S, and S-Cap rats. Similarly, the increase in perivascular fibrosis was greatest in AB rats, and there was no difference among AB-Cap, S, and S-Cap rats. These data suggest that the RAS, independent of increased arterial pressure, is critical for the development of the vascular and fibrotic changes that occur in this model of pressure overload hypertrophy.

scholarly journals Rats are protected from the stress of chronic pressure overload compared with mice

2020 ◽  
Vol 318 (5) ◽  
pp. R894-R900 ◽  
Author(s):  
Koichi Nishimura ◽  
Marko Oydanich ◽  
Jie Zhang ◽  
Denis Babici ◽  
Diego Fraidenraich ◽  
...  
Keyword(s):  
Troponin I ◽  
Diastolic Pressure ◽  
Pressure Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Pressure Gradients ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Systolic And Diastolic Function ◽  
Systolic Wall Stress

The goal of this investigation was to compare the effects of chronic (4 wk) transverse aortic constriction (TAC) in Sprague-Dawley rats and C57BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats ( n = 7) and mice ( n = 7) (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4 wk, the percent increase in LV hypertrophy, as reflected by LV/tibial length (51% vs 49%), was similar in rats ( n = 12) and mice ( n = 12). After 4 wk of TAC, LV systolic and diastolic function were preserved in TAC rats. In contrast, in TAC mice, LV ejection fraction decreased by 31% compared with sham, along with increases in LV end-diastolic pressure (153%) and LV systolic wall stress (86%). Angiogenesis, as reflected by Ki67 staining of capillaries, increased more in rats ( n = 6) than in mice ( n = 6; 10 ± 2 vs. 6 ± 1 Ki67-positive cells/field). Myocardial blood flow fell by 55% and coronary reserve by 28% in mice with TAC ( n = 4), but they were preserved in rats ( n = 4). Myogenesis, as reflected by c-kit-positive myocytes staining positively for troponin I, is another mechanism that can confer protection after TAC. However, the c-kit-positive cells in rats with TAC were all negative for troponin I, indicating the absence of myogenesis. Thus, rats showed relative tolerance to severe pressure overload compared with mice, with mechanisms involving angiogenesis but not myogenesis.

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