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 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.

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 Therapeutic Evaluation of Antibody-Based Targeted Delivery of Interleukin 9 in Experimental Pulmonary Hypertension

2021 ◽  
Vol 22 (7) ◽  
pp. 3460
Author(s):  
Baptiste Gouyou ◽  
Katja Grün ◽  
Anne Kerschenmeyer ◽  
Alessandra Villa ◽  
Mattia Matasci ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Targeted Delivery ◽  
Ventricular Remodeling ◽  
Treatment Strategies ◽  
Ventricular Myocardium ◽  
Pulmonary Vasculature ◽  
Heart Catheterization ◽  
Echocardiographic Parameters ◽  
Interleukin 9

Background and Aims: Pulmonary hypertension (PH) is a heterogeneous disorder associated with poor prognosis. For the majority of patients, only limited therapeutic options are available. Thus, there is great interest to develop novel treatment strategies focusing on pulmonary vascular and right ventricular remodeling. Interleukin 9 (IL9) is a pleiotropic cytokine with pro- and anti-inflammatory functions. The aim of this study was to evaluate the therapeutic activity of F8IL9F8 consisting of IL9 fused to the F8 antibody, specific to the alternatively-spliced EDA domain of fibronectin, which is abundantly expressed in pulmonary vasculature and right ventricular myocardium in PH. Methods: The efficacy of F8IL9F8 in attenuating PH progression in the monocrotaline mouse model was evaluated in comparison to an endothelin receptor antagonist (ERA) or an IL9 based immunocytokine with irrelevant antibody specificity (KSFIL9KSF). Treatment effects were assessed by right heart catheterization, echocardiography as well as histological and immunohistochemical tissue analyses. Results: Compared to controls, systolic right ventricular pressure (RVPsys) was significantly elevated and a variety of right ventricular echocardiographic parameters were significantly impaired in all MCT-induced PH groups except for the F8IL9F8 group. Both, F8IL9F8 and ERA treatments lead to a significant reduction in RVPsys and an improvement of echocardiographic parameters when compared to the MCT group not observable for the KSFIL9KSF group. Only F8IL9F8 significantly reduced lung tissue damage and displayed a significant decrease of leukocyte and macrophage accumulation in the lungs and right ventricles. Conclusions: Our study provides first pre-clinical evidence for the use of F8IL9F8 as a new therapeutic agent for PH in terms of a disease-modifying concept addressing cardiovascular remodeling.

scholarly journals Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure

2015 ◽  
Vol 308 (8) ◽  
pp. L797-L806 ◽  
Author(s):  
Kara N. Goss ◽  
Anthony R. Cucci ◽  
Amanda J. Fisher ◽  
Marjorie Albrecht ◽  
Andrea Frump ◽  
...  
Keyword(s):  
Lung Injury ◽  
Right Ventricular ◽  
Ventricular Remodeling ◽  
Systolic Pressure ◽  
Sprague Dawley ◽  
Hypoxia Exposure ◽  
Hyperoxia Exposure ◽  
Hyperoxic Lung Injury ◽  
Negative Impacts

The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0–4 or 0–10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm = 362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults.

Wnt Signaling Pathway in Right Ventricular Remodeling

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
A Tretyn ◽  
KD Schlüter ◽  
W Janssen ◽  
HA Ghofrani ◽  
F Grimminger ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Ventricular Remodeling ◽  
Wnt Signaling Pathway ◽  
Right Ventricular Remodeling

Pulmonary Vascular Versus Right Ventricular Function Changes During Targeted Therapies of Pulmonary Hypertension – An Argument for Upfront Combination Therapy?

2012 ◽  
Vol 8 (3) ◽  
pp. 209
Author(s):  
Wouter Jacobs ◽  
Anton Vonk-Noordegraaf ◽  
◽  
Keyword(s):  
Combination Therapy ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Meta Analysis ◽  
Right Heart Failure ◽  
Functional Class ◽  
Pulmonary Vasculature ◽  
The Right

Pulmonary arterial hypertension is a progressive disease of the pulmonary vasculature, ultimately leading to right heart failure and death. Current treatment is aimed at targeting three different pathways: the prostacyclin, endothelin and nitric oxide pathways. These therapies improve functional class, increase exercise capacity and improve haemodynamics. In addition, data from a meta-analysis provide compelling evidence of improved survival. Despite these treatments, the outcome is still grim and the cause of death is inevitable – right ventricular failure. One explanation for this paradox of haemodynamic benefit and still worse outcome is that the right ventricle does not benefit from a modest reduction in pulmonary vascular resistance. This article describes the physiological concepts that might underlie this paradox. Based on these concepts, we argue that not only a significant reduction in pulmonary vascular resistance, but also a significant reduction in pulmonary artery pressure is required to save the right ventricle. Haemodynamic data from clinical trials hold the promise that these haemodynamic requirements might be met if upfront combination therapy is used.

scholarly journals Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thiago Ferreira de Souza ◽  
Thiago Quinaglia Silva ◽  
Lígia Antunes-Correa ◽  
Zsofia D. Drobni ◽  
Felipe Osório Costa ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Right Ventricular ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Systolic Dysfunction ◽  
Extracellular Volume ◽  
Increased Risk ◽  
Tissue Characteristics ◽  
A Prospective Study

AbstractThere are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310–517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = −0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

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