Experimental Models of Right Heart Failure: A Window for Translational Research in Pulmonary Hypertension

Guihaire, Julien; Bogaard, Harm Jan; Flécher, Erwan; Noly, Pierre‐Emmanuel; Mercier, Olaf; Haddad, François; Fadel, Élie

doi:10.1055/s-0033-1355444

Cited by 35 publications

(14 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MCT also contributes to kidney injury as demonstrated by significantly increased serum creatinine ( [38]. However, MCT-related toxicity to the myocardium restricts the relevance of this model to study right ventricular failure [80].…”

Section: Mitral Valve Regurgitationmentioning

confidence: 99%

See 1 more Smart Citation

Current animal models for the study of congestion in heart failure: an overview

et al. 2019

View full text Add to dashboard Cite

Congestion (i.e., backward failure) is an important culprit mechanism driving disease progression in heart failure. Nevertheless, congestion remains often underappreciated and clinicians underestimate the importance of congestion on the pathophysiology of decompensation in heart failure. In patients, it is however difficult to study how isolated congestion contributes to organ dysfunction, since heart failure and chronic kidney disease very often coexist in the so-called cardiorenal syndrome. Here, we review the existing relevant and suitable backward heart failure animal models to induce congestion, induced in the left-(i.e., myocardial infarction, rapid ventricular pacing) or right-sided heart (i.e., aorta-caval shunt, mitral valve regurgitation, and monocrotaline), and more specific animal models of congestion, induced by saline infusion or inferior vena cava constriction. Next, we examine critically how representative they are for the clinical situation. After all, a relevant animal model of isolated congestion offers the unique possibility of studying the effects of congestion in heart failure and the cardiorenal syndrome, separately from forward failure (i.e., impaired cardiac output). In this respect, new treatment options can be discovered.

show abstract

Section: Mitral Valve Regurgitationmentioning

confidence: 99%

“…Pulmonary artery banding (PAB) causes chronic pressure overload leading to right-sided heart failure and is performed by placing a suture, clip, or inflatable ring around the pulmonary artery proximally to the right ventricle [80]. [39,40].…”

Section: Pulmonary Artery Bandingmentioning

confidence: 99%

Current animal models for the study of congestion in heart failure: an overview

et al. 2019

View full text Add to dashboard Cite

show abstract

“…16,20,21 Table 2 summarizes normative values for the measures of function of the right side of the heart, and Figure 2 illustrates some of these measures. 16,[22][23][24][25][26][27][28][29][30][31] As discussed in the following paragraphs, myocardial deformation imaging is also emerging as a useful modality for imaging the right side of the heart. Several pearls are important in evaluating the cardiopulmonary unit by echocardiography.…”

Section: Overview Of Echocardiographic Evaluationmentioning

confidence: 99%

“…There is limited experience 98 with the technique in PAH, however. 31 Phophorus magnetic resonance spectroscopy studies performed in patients with advanced LV failure have repeatedly demonstrated decreased myocardial levels of creatine and ATP and correlations between these levels and survival. 99 …”

Section: Molecular and Perfusion Imaging Magnetic Resonance Spectroscopymentioning

confidence: 99%

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

et al. 2015

View full text Add to dashboard Cite

899N oninvasive imaging plays a key role in both the diagnosis and management of patients with pulmonary hypertension (PH). In recent years, there have been 2 major changes in perspective of imaging in PH. The first was the realization that imaging should focus on the evaluation of not only the pulmonary pressures but also the cardiopulmonary unit ( Figure 1). 1,2The second was the emergence of multimodality imaging with a complementary role for echocardiography, magnetic resonance (MRI), computed tomography, and positron emission tomography (PET).2-7 These techniques not only help in the diagnosis of PH but also help identify factors that determine risk and prognosis and gauge therapeutic effects on right ventricular (RV) function in patients with pulmonary arterial hypertension (PAH). Although echocardiography is the mainstay in the assessment of hemodynamic and ventricular function in PH, MRI has emerged as the gold standard for quantifying volumes, function, and flow in the right side of the heart. 2-7 PET is also offering novel insights into perfusion and blood flow, metabolism, neurohormonal activation, and other molecular processes in the right side of the heart but is used mainly for research at this time. Catheterization of the right side of the heart remains the gold standard for defining PH and assessing hemodynamics both at rest and with exercise. Invasive assessment of cardiac output (CO) may, however, have limited accuracy when assumed instead of measured oxygen consumption is used to derive CO (eg, using the Fick method) or when thermodilution is used in the setting of a low-CO state. [8][9][10] This review covers RV imaging studies performed in the field of PH and discusses recent advances in echocardiography and cardiac MRI and PET imaging for detailed assessment of RV function. The review starts with a discussion of important physiological considerations and unmet needs in imaging research of the right side of the heart in PH. Computed tomography angiography, which plays an important role in evaluating chronic thromboembolic PH, is not discussed extensively in this review. Physiological ConsiderationsAlthough PH is a syndrome affecting the pulmonary vasculature, survival of patients with PH is closely related to RV function. 1,[11][12][13][14] The RV initially adapts to the increased afterload by increasing its wall thickness and contractility. These mechanisms are, however, often insufficient, and RV dysfunction eventually occurs. After the recent Fifth World Symposium on Pulmonary Hypertension, a definition of failure of the right side of the heart secondary to PH was adopted: "Right heart failure in the setting of PH can be defined as a complex clinical syndrome due to a suboptimal delivery of blood or elevated systemic venous pressure at rest or exercise as a consequence of elevated RV afterload."2 The proposed definition takes into account both the systolic and diastolic characteristics of function of the right side of the heart, as well as physiological demands such as exercise.In underst...

show abstract

“…For instance, in the chronic hypoxic exposure or monocrotaline (MCT)-induced rat models, pulmonary hypertension rarely develops with the same severity observed in humans perhaps due to the absence of obstructive intimal lesions in the peripheral pulmonary arteries [65, 66]. Furthermore, the chronic hypoxia model does not lead to RV failure, while MCT injection causes myocarditis affecting both ventricles and causing liver and kidney damage [67]. These limitations may explain why it is difficult to translate the reversal of PAH in animal models by several experimental compounds into therapies for PAH patients.…”

Section: Animal Models Of Pahmentioning

confidence: 99%

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension

Orriols

Gomez‐Puerto

Dijke

2017

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. The most common cause of PAH is inactivating mutations in the gene encoding a bone morphogenetic protein type II receptor (BMPRII). Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease. Emerging data suggest that restoration of BMPRII signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. Here we will focus on recent advances in rescuing BMPRII expression, function or signaling to prevent and reverse pulmonary vascular remodeling in PAH and its feasibility for clinical translation. Furthermore, we summarize the role of described miRNAs that directly target the BMPR2 gene in blood vessels. We discuss the therapeutic potential and the limitations of promising new approaches to restore BMPRII signaling in PAH patients. Different mutations in BMPR2 and environmental/genetic factors make PAH a heterogeneous disease and it is thus likely that the best approach will be patient-tailored therapies.

show abstract

Experimental Models of Right Heart Failure: A Window for Translational Research in Pulmonary Hypertension

Cited by 35 publications

References 75 publications

Current animal models for the study of congestion in heart failure: an overview

Current animal models for the study of congestion in heart failure: an overview

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension

Contact Info

Product

Resources

About