The distribution of the obstruction in the pulmonary arteries modifies pulsatile right ventricular afterload in pulmonary hypertension

Ruiz-Cano, María J.; Grignola, Juan C.; Barberà, Joan Albert; García, Silvia García; Salvador, María Lázaro; Escribano, Pilar

doi:10.1016/j.ijcard.2014.11.118

Cited by 8 publications

(5 citation statements)

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“…In this condition, elevated wall stresses develop in the RV lateral free wall and outflow tract and then the RVH [ 29 , 30 ]. Initially, RVH can be compensatory to preserve RV function, particularly because of its ability to increase contractility and to preserve efficient management of the pulmonary vascular lesion; however, RVH is still ongoing, characterized by an increase in cardiomyocyte size and fibrosis, and leads to enlargement of the heart, depression of contractile function and, eventually, right HF [ 31 , 32 ]. Therefore, failed adaption of the RV to the increased afterload is the main cause of death in patients with PAH [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

Yang

et al. 2016

PLoS ONE

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BackgroundPulmonary arterial hypertension is characterized by increased pressure overload that leads to right ventricular hypertrophy (RVH). GPR91 is a formerly orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate; however, its role in RVH remains unknown.Methods and ResultsWe investigated the role of succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH induced by pressure overload in SD rats. GPR91 was shown to be located in cardiomyocytes. In the sham and PAB rats, succinate treatment further aggravated RVH, up-regulated RVH-associated genes and increased p-Akt/t-Akt levels in vivo. In vitro, succinate treatment up-regulated the levels of the hypertrophic gene marker anp and p-Akt/t-Akt in cardiomyocytes. All these effects were inhibited by the PI3K antagonist wortmannin both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up-regulated compared to that in human RVH.ConclusionsOur findings indicate that succinate-GPR91 signaling may be involved in RVH via PI3K/Akt signaling in vivo and in vitro. Therefore, GPR91 may be a novel therapeutic target for treating pressure overload-induced RVH.

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Section: Discussionmentioning

confidence: 99%

The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

Yang

et al. 2016

PLoS ONE

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“…Although a single unresolved event such as the presence of a thrombotic occlusion in one of the pulmonary arteries is usually responsible for the development of CTPEH, in patients with the most severe forms of the disease small vessel arteriopathy with microvasculature remodeling is often observed (McNeil and Dunning, 2007 ). It is understood that these changes in the peripheral vasculature have an important yet still unclear functional role in further raising PVR (Ruiz-Cano et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

The Use of Biophysical Flow Models in the Surgical Management of Patients Affected by Chronic Thromboembolic Pulmonary Hypertension

et al. 2018

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Introduction: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) results from progressive thrombotic occlusion of the pulmonary arteries. It is treated by surgical removal of the occlusion, with success rates depending on the degree of microvascular remodeling. Surgical eligibility is influenced by the contributions of both the thrombus occlusion and microvasculature remodeling to the overall vascular resistance. Assessing this is challenging due to the high inter-individual variability in arterial morphology and physiology. We investigated the potential of patient-specific computational flow modeling to quantify pressure gradients in the pulmonary arteries of CTEPH patients to assist the decision-making process for surgical eligibility.Methods: Detailed segmentations of the pulmonary arteries were created from postoperative chest Computed Tomography scans of three CTEPH patients. A focal stenosis was included in the original geometry to compare the pre- and post-surgical hemodynamics. Three-dimensional flow simulations were performed on each morphology to quantify velocity-dependent pressure changes using a finite element solver coupled to terminal 2-element Windkessel models. In addition to transient flow simulations, a parametric modeling approach based on constant flow simulations is also proposed as faster technique to estimate relative pressure drops through the proximal pulmonary vasculature.Results: An asymmetrical flow split between left and right pulmonary arteries was observed in the stenosed models. Removing the proximal obstruction resulted in a reduction of the right-left pressure imbalance of up to 18%. Changes were also observed in the wall shear stresses and flow topology, where vortices developed in the stenosed model while the non-stenosed retained a helical flow. The predicted pressure gradients from constant flow simulations were consistent with the ones measured in the transient flow simulations.Conclusion: This study provides a proof of concept that patient-specific computational modeling can be used as a noninvasive tool for assisting surgical decisions in CTEPH based on hemodynamics metrics. Our technique enables determination of the proximal relative pressure, which could subsequently be compared to the total pressure drop to determine the degree of distal and proximal vascular resistance. In the longer term this approach has the potential to form the basis for a more quantitative classification system of CTEPH types.

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“…It has been proposed that a unique feature of the pulmonary circulation is that PVR and total arterial compliance are tightly coupled through an inverse hyperbolic relationship, resulting in a constant RC-time product that prevails in both health and disease [8][9][10][11][12][13][14][15][16][17][18][19][20][21]. A constant RC-time product has important implications for the assessment of RV afterload, namely that PVR and total arterial compliance are redundant measurements and knowledge of one enables the derivation of the other.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary vascular resistance and compliance relationship in pulmonary hypertension

et al. 2015

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Right ventricular adaptation to the increased pulmonary arterial load is a key determinant of outcomes in pulmonary hypertension (PH). Pulmonary vascular resistance (PVR) and total arterial compliance (C) quantify resistive and elastic properties of pulmonary arteries that modulate the steady and pulsatile components of pulmonary arterial load, respectively. PVR is commonly calculated as transpulmonary pressure gradient over pulmonary flow and total arterial compliance as stroke volume over pulmonary arterial pulse pressure (SV/PApp). Assuming that there is an inverse, hyperbolic relationship between PVR and C, recent studies have popularised the concept that their product (RC-time of the pulmonary circulation, in seconds) is "constant" in health and diseases. However, emerging evidence suggests that this concept should be challenged, with shortened RC-times documented in post-capillary PH and normotensive subjects. Furthermore, reported RC-times in the literature have consistently demonstrated significant scatter around the mean. In precapillary PH, the true PVR can be overestimated if one uses the standard PVR equation because the zero-flow pressure may be significantly higher than pulmonary arterial wedge pressure. Furthermore, SV/PApp may also overestimate true C. Further studies are needed to clarify some of the inconsistencies of pulmonary RC-time, as this has major implications for our understanding of the arterial load in diseases of the pulmonary circulation. @ERSpublications Empiric estimates of pulmonary arterial load are prone to errors and may result in overestimation of RC-time

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The distribution of the obstruction in the pulmonary arteries modifies pulsatile right ventricular afterload in pulmonary hypertension

Cited by 8 publications

References 9 publications

The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

The Use of Biophysical Flow Models in the Surgical Management of Patients Affected by Chronic Thromboembolic Pulmonary Hypertension

Pulmonary vascular resistance and compliance relationship in pulmonary hypertension

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