Clinical relevance of right ventricular diastolic stiffness in pulmonary hypertension

Trip, Pia; Rain, Silvia; Handoko, Louis; Bruggen, Cathelijne Van der; Bogaard, Harm Jan; Marcus, Tim; Boonstra, Anco; Westerhof, Nico; Noordegraaf, Anton Vonk; Man, Frances de

doi:10.1183/13993003.congress-2015.oa3522

Cited by 37 publications

(86 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Five-six weeks after SuHx exposure, we observed significantly increased AOT and circumferential stresses in RV myocardial tissues subjected to equibiaxial strain compared with normotensive control samples. Since RV myocardial fibrosis has been observed in pulmonary hypertension [2][3][4], we also investigated whether the mechanical properties of the RV myocardial extracellular matrix were altered in this PAH model by retesting RV samples after they had been decellularized. Extracellular matrix samples from PAH rats were significantly stiffer in the circumferential but not AOT direction than decellularized control samples.…”

Section: Discussionmentioning

confidence: 99%

“…Right ventricular (RV) function is a good prognostic indicator in pulmonary arterial hypertension (PAH), a progressive vasculopathy that commonly results in intractable RV failure and premature death [1]. It has been shown in humans with and animal models of PAH [2][3][4] that the RV hypertrophies, in response to increased RV systolic pressure, can be associated with tissue fibrosis and altered end-diastolic stiffness.…”

Section: Introductionmentioning

confidence: 99%

“…Since RV myocardial fibrosis has also been reported in humans [2,4] and animals [3] with pulmonary hypertension, we further investigated whether the mechanical properties of the RV myocardial extracellular matrix (ECM) were altered during pulmonary arterial hypertension by retesting RV samples after they had been decellularized. Stress-strain measurements from biaxial testing protocols obtained from mechanical testing of intact and decellularized RV tissues were well approximated by the anisotropic exponential strain-energy function first proposed by Fung [10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Relative Contributions of Matrix and Myocytes to Biaxial Mechanics of the Right Ventricle in Pulmonary Arterial Hypertension

Vélez-Rendón

Pursell

Shieh

et al. 2019

Journal of Biomechanical Engineering

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) commonly leads to right ventricular (RV) hypertrophy and fibrosis that affect the mechanical properties of the RV myocardium (MYO). To investigate the effects of PAH on the mechanics of the RV MYO and extracellular matrix (ECM), we compared RV wall samples, isolated from rats in which PAH was induced using the SuHx protocol, with samples from control animals before and after the tissues were decellularized. Planar biaxial mechanical testing, a technique first adapted to living soft biological tissues by Fung, was performed on intact and decellularized samples. Fung's anisotropic exponential strain energy function fitted the full range of biaxial test results with high fidelity in control and PAH samples both before and after they were decellularized. Mean RV myocardial apex-to-outflow tract and circumferential stresses during equibiaxial strain were significantly greater in PAH than control samples. Mean RV ECM circumferential but not apex-to-outflow tract stresses during equibiaxial strain were significantly greater in the PAH than control group. The ratio of ECM to myocardial stresses at matched strains did not change significantly between groups. Circumferential stresses were significantly higher than apex-to-outflow tract stresses for all groups. These findings confirm the predictions of a mathematical model based on changes in RV hemodynamics and morphology in rat PAH, and may provide a foundation for a new constitutive analysis of the contributions of ECM remodeling to changes in RV filling properties during PAH.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relative Contributions of Matrix and Myocytes to Biaxial Mechanics of the Right Ventricle in Pulmonary Arterial Hypertension

Vélez-Rendón

Pursell

Shieh

et al. 2019

Journal of Biomechanical Engineering

View full text Add to dashboard Cite

show abstract

“…If overload surpasses its capacity to adapt, the RV suffers maladaptive remodelling and begins to fail, leading to decreased cardiac output and ultimately death . RV dysfunction is the main determinant of PAH prognosis, and recent studies have shown that RV diastolic dysfunction is also present in PAH patients and is associated with the disease severity . These patients present increased RV cardiomyocyte hypertrophy and fibrosis, as well as increased RV cardiomyocyte tension development and calcium sensitivity Thus, therapies focusing on RV diastolic stiffness should effectively improve the prognosis of patients with PAH .…”

Section: Discussionmentioning

confidence: 99%

“…Patients with pulmonary arterial hypertension (PAH) develop heart failure (HF) due to a progressive increase in right ventricular (RV) pressure overload . Although it is known for some years that RV systolic adaptation is of clinical importance, it just recently became clear that RV diastolic stiffness increases and may contribute to disease progression in PAH . Hypertrophy, fibrosis and stiffening of the RV cardiomyocytes all appeared to contribute to the observed RV diastolic stiffness.…”

Section: Introductionmentioning

confidence: 99%

Neuregulin‐1 attenuates right ventricular diastolic stiffness in experimental pulmonary hypertension

Adão

Mendes-Ferreira

Maia-Rocha

et al. 2018

Clin Exp Pharma Physio

View full text Add to dashboard Cite

We have previously shown that treatment with recombinant human neuregulin-1 (rhNRG-1) improves pulmonary arterial hypertension (PAH) in a monocrotaline (MCT)-induced animal model, by decreasing pulmonary arterial remodelling and endothelial dysfunction, as well as by restoring right ventricular (RV) function.Additionally, rhNRG-1 treatment showed direct myocardial anti-remodelling effects in a model of pressure loading of the RV without PAH. This work aimed to study the intrinsic cardiac effects of rhNRG-1 on experimental PAH and RV pressure overload, and more specifically on diastolic stiffness, at both the ventricular and cardiomyocyte level. We studied the effects of chronic rhNRG-1 treatment on ventricular passive stiffness in RV and LV samples from MCT-induced PAH animals and in the RV from animals with compensated and decompensated RV hypertrophy, through a mild and severe pulmonary artery banding (PAB). We also measured passive tension in isolated cardiomyocytes and quantified the expression of myocardial remodelling-associated genes and calcium handling proteins. Chronic rhNRG-1 treatment decreased passive tension development in RV and LV isolated from animals with MCT-induced PAH. This decrease was associated with increased phospholamban phosphorylation, and with attenuation of the expression of cardiac maladaptive remodelling markers.Finally, we showed that rhNRG-1 therapy decreased RV remodelling and cardiomyocyte passive tension development in PAB-induced RV hypertrophy animals, without compromising cardiac function, pointing to cardiac-specific effects in both hypertrophy stages. In conclusion, we demonstrated that rhNRG-1 treatment decreased RV intrinsic diastolic stiffness, through the improvement of calcium handling and cardiac remodelling signalling. K E Y W O R D Sdiastolic function, diastolic stiffness, neuregulin-1, pulmonary arterial hypertension, right ventricle

show abstract

A clinically applicable strategy to estimate the in vivo distribution of mechanical material properties of the right ventricular wall

Wong

Simon

et al. 2021

Numer Methods Biomed Eng

View full text Add to dashboard Cite

A clinically applicable approach to estimate the in vivo mechanical material properties of the heart wall is presented. This optimization-based inverse estimation approach applies a shape-based objective functional combined with rigid body registration and incremental parameterization of heterogeneity to use standard clinical imaging data along with simplified representations of cardiac function to provide consistent and physically meaningful solution estimates. The capability of the inverse estimation algorithm is evaluated through

show abstract

Clinical relevance of right ventricular diastolic stiffness in pulmonary hypertension

Cited by 37 publications

References 0 publications

Relative Contributions of Matrix and Myocytes to Biaxial Mechanics of the Right Ventricle in Pulmonary Arterial Hypertension

Relative Contributions of Matrix and Myocytes to Biaxial Mechanics of the Right Ventricle in Pulmonary Arterial Hypertension

Neuregulin‐1 attenuates right ventricular diastolic stiffness in experimental pulmonary hypertension

A clinically applicable strategy to estimate the in vivo distribution of mechanical material properties of the right ventricular wall

Contact Info

Product

Resources

About