Animal models of right heart failure

Abstract

Right heart failure may be the ultimate cause of death in patients with acute or chronic pulmonary hypertension (PH). As PH is often secondary to other cardiovascular diseases, the treatment goal is to target the underlying disease. We do however know, that right heart failure is an independent risk factor, and therefore, treatments that improve right heart function may improve morbidity and mortality in patients with PH. There are no therapies that directly target and support the failing right heart and translation from therapies that improve left heart failure have been unsuccessful, with the exception of mineralocorticoid receptor antagonists. To understand the underlying pathophysiology of right heart failure and to aid in the development of new treatments we need solid animal models that mimic the pathophysiology of human disease. There are several available animal models of acute and chronic PH. They range from flow induced to pressure overload induced right heart failure and have been introduced in both small and large animals.When initiating new pre-clinical or basic research studies it is key to choose the right animal model to ensure successful translation to the clinical setting. Selecting the right animal model for the right study is hence important, but may be difficult due to the plethora of different models and local availability. In this review we provide an overview of the available animal models of acute and chronic right heart failure and discuss the strengths and limitations of the different models.

Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism

“…As reviewed by Stenmark et al, though, no current animal model of PAH perfectly recapitulates all features of the human disease(146). Additionally, this special issue also extensively discusses the strengths and weaknesses of various animal models of RV failure elsewhere(147). The study of RV failure in human subjects at the molecular level is inherently limited by the availability and quality of tissues available from patients, often post-mortem or at end stage.…”

Getting to the bottom of right heart failure

“…Moreover, the authors discuss the increased relevance of myocardial passive stiffness and active cardiomyocyte relaxation (e.g., altered cytosolic Ca2+/Na+ signaling) in this specific disease. Consistent with the overall topic of this special issue, they highlight RV dysfunction in HFpEF and provide possible explanations for RV dysfunction Following the above mechanistic basic-translational s c i e n c e a r t i c l e s o n RV a n d LV d y s f u n c t i o n a n d interdependence, Andersen et al (12) give a very insightful State-of-the-Art review on "Animal models of Right Ventricular failure". After an introduction on animal models of RV failure, the authors discuss different modes of therapeutic targets, advantages and disadvantages in different species and models, and define RV failure in animal models.…”

RNA expression profiles and regulatory networks in human right ventricular hypertrophy due to high pressure load

“…On the non-coding RNA level, we report for the first time miRNAs, lncRNAs, and circRNAs associated with human RVH ( Tables S2–S4 ). To our knowledge, previous reports identified several miRNAs associated with either LVH in high pressure afterload models ( Mohan et al., 2018 ; Rau et al., 2017 ; Wehbe et al., 2019 ), RVH in rodent pulmonary artery (PA) banding models ( Andersen et al., 2020 ; Reddy and Bernstein, 2015 ; Reddy et al., 2012 ; Thum and Batkai, 2014 ), or human RVH with postmortem control samples ( Bittel et al., 2014 ; O'Brien et al., 2012 ; Wang et al., 2014 ; Zhang et al., 2013 ). We did not find any of the miRNAs previously reported in cardiac hypertrophy of animals or humans, with the exception of miR-216a and miR-217, which were downregulated in human compensated RVH in our study (see the supplemental information for extended discussion).…”

“…Right ventricular hypertrophy may occur in the setting of RV outflow tract obstruction (PS; normal pulmonary vascular resistance) or in hypertensive pulmonary vascular disease with anatomically normal RV outflow ( Hansmann, 2017 ; Hansmann et al., 2019 ; Santens et al., 2020 ). Both etiologies have been studied in various animal models ( Andersen et al., 2020 ); however, none of them fully simulate human RVH in vivo ( Agrawal et al., 2020 ; Andersen et al., 2020 ; Bernardo et al., 2020 ; Santens et al., 2020 ).…”