Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction

Borgdorff, M. A. J.; Koop, A M C; Bloks, Vincent W.; Dickinson, Michael G.; Steendijk, Paul; Silljé, Herman H W; Wiechen, Maarten P.H. Van; Berger, Rolf M. F.; Bartelds, Beatrijs

doi:10.1016/j.yjmcc.2014.11.024

Cited by 39 publications

(56 citation statements)

References 40 publications

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“…It was shown that ventricular-arterial coupling predicts outcome in PH patients (Vanderpool et al, 2015) and further clinical data indicate that progression of PAH-associated RV dysfunction leads to RV failure with increased RV contractility but importantly, impaired RV ventricular-coupling in most patients (Kuehne et al, 2004;Galie et al, 2007), while a subgroup of patients adapt with preserved contractility and compensated RV hypertrophy (Rich et al, 2010;Tedford et al, 2013). Accordingly, a recently published experimental study by Borgdorff and co-workers demonstrates that rats develop either clinical signs of heart failure upon tight pulmonary artery banding or adapt without signs of heart failure (Borgdorff et al, 2015b). Importantly, while indices of systolic function deteriorate upon chronic pressure-overload as compared with sham-operated animals, pressure-volume loop-derived contractility measures indicate a hyper-contractile RV -even in animals with clinical signs of heart failure -accompanied by ventricular-arterial decoupling.…”

Section: Discussionmentioning

confidence: 99%

“…were reported (Faber et al, 2006;Bartelds et al, 2011;Kapur et al, 2013;Borgdorff et al, 2013Borgdorff et al, , 2015bde Raaf et al, 2015;Szulcek et al, 2016). However, opening the chest and insertion of the catheter through the RV free wall cause loss of intrathoracic pressure, changes of myocardial integrity and trauma.…”

Section: Introductionmentioning

confidence: 91%

“…Consequently, the accurate assessment of RV indices by non-invasive imaging along with intra-cardiac measures are essential to diagnose rising filling pressures, diastolic dysfunction and reduced ejection volumes (Voelkel et al, 2006;Pokreisz et al, 2007;Borgdorff et al, 2015b).…”

Section: Introductionmentioning

confidence: 99%

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Maintained right ventricular pressure overload induces ventricular–arterial decoupling in mice

Böehm

Lawrie

Wilhelm

et al. 2017

Experimental Physiology

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This is the peer reviewed version of the following article: Boehm, M. et al (2016), Maintained right ventricular pressure overload induces ventricular-arterial decoupling in mice. Exp Physiol., which has been published in final form at https://doi.org/10.1113/EP085963. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request.This is an Accepted Article that has been peer-reviewed and approved for publication in the Experimental Physiology, but has yet to undergo copy-editing and proof correction. Please cite this article as an Accepted Article; doi: 10.1113/EP085963. This article is protected by copyright. All rights reserved. AbstractNew Findings: What is the central question of this study?The aim is to investigate whether complementary assessment of non-invasive ultrasound imaging along with closed chest-derived intra-cardiac pressure-volume catheterization is applicable to mice for an in-depth characterization of right ventricular (RV) function even upon maintained pressure overload. What is the main finding and its importance?Characterization

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

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Maintained right ventricular pressure overload induces ventricular–arterial decoupling in mice

Böehm

Lawrie

Wilhelm

et al. 2017

Experimental Physiology

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“…Rats have been reported to survive up to 22 weeks in such condition, despite (near) systemic RV pressures [28]. However, a tighter PAB has been demonstrated to lead to clinical symptoms of RV failure, i.e., inactivity, decreased cleaning behavior (raised fur), poor peripheral circulation, dyspnea/tachypnea, ascites and pleural/pericardial effusions and, ultimately, mortality in a high percentage of animals [17, 29–31]. High-intensity exercise capacity [32] and voluntary low-intensity exercise [8, 16, 17] are reduced in this model.…”

Section: Modeling and Evaluating A Unique Ventriclementioning

confidence: 99%

“…Evidence is accumulating that RV failure due to chronic pressure load is characterized by both enhanced systolic function and progressive deterioration of diastolic function [16, 31, 34]. Sparse clinical data show that in PH patients, higher right atrial pressure (an indirect measure of RV diastolic function) is associated with worse outcome.…”

Section: The Physiology Of Rv Adaptation To Increased Afterloadmentioning

confidence: 99%

Right ventricular failure due to chronic pressure load: What have we learned in animal models since the NIH working group statement?

et al. 2015

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Right ventricular (RV) failure determines outcome in patients with pulmonary hypertension, congenital heart diseases and in left ventricular failure. In 2006, the Working Group on Cellular and Molecular Mechanisms of Right Heart Failure of the NIH advocated the development of preclinical models to study the pathophysiology and pathobiology of RV failure. In this review, we summarize the progress of research into the pathobiology of RV failure and potential therapeutic interventions. The picture emerging from this research is that RV adaptation to increased afterload is characterized by increased contractility, dilatation and hypertrophy. Clinical RV failure is associated with progressive diastolic deterioration and disturbed ventricular–arterial coupling in the presence of increased contractility. The pathobiology of the failing RV shows similarities with that of the LV and is marked by lack of adequate increase in capillary density leading to a hypoxic environment and oxidative stress and a metabolic switch from fatty acids to glucose utilization. However, RV failure also has characteristic features. So far, therapies aiming to specifically improve RV function have had limited success. The use of beta blockers and sildenafil may hold promise, but new therapies have to be developed. The use of recently developed animal models will aid in further understanding of the pathobiology of RV failure and development of new therapeutic strategies.

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Volume load‐induced right ventricular dysfunction in animal models: insights in a translational gap in congenital heart disease

Bossers

Hagdorn

Ploegstra

et al. 2017

European J of Heart Fail

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809 Hedges' g (95% CI) 0.2 (-1.0-1.5) Study Regurgitation models (n=135): P=0.737, I2=90.6% ) COMBINED (n=280): P=0.005, I2=86.7% 0 -7,5 7,5 Hedges' g (95% CI) 4.Study Regurgitation models (n=109): P<0.001, I2=61.0% Shunt models (n=81): P<0.001, I2=88.2% Ruzicka 1993, 7d (n=16) Ruzicka 1993, 28d (n=16) Szabó 2006, 90d (n=18) Bartelds 2011, 30d (n=11) Borgdorff 2012, 28d (n=20) COMBINED (n=190): P<0.001, I2=84.8%

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Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction

Cited by 39 publications

References 40 publications

Maintained right ventricular pressure overload induces ventricular–arterial decoupling in mice

Maintained right ventricular pressure overload induces ventricular–arterial decoupling in mice

Right ventricular failure due to chronic pressure load: What have we learned in animal models since the NIH working group statement?

Volume load‐induced right ventricular dysfunction in animal models: insights in a translational gap in congenital heart disease

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