Anne-Marie Koop

2 29 INTRODUCTION Right ventricular failure (RVF) due to increased pressure load is a primary risk factor for morbidity and mortality in patients with congenital heart diseases as well as in patients with pulmonary hypertension (PH). 1,2 Moreover, RV dysfunction has also been demonstrated to be an important prognostic determinant in left ventricular failure. 3 Unfortunately, the pathophysiology of RV failure is yet insufficiently understood, 4 which precludes the development of RV specific treatments. Research into these mechanisms is hampered by the lack of a model reflecting clinical RVF. It is in this perspective that a National Heart, Lung and Blood Institute working group on cellular and molecular mechanisms of right heart failure stated that ‘researchers must develop reliable, reproducible and relevant animal models of RV failure’. 5 Since RV function is a critical prognostic determinant in PH, 2 RVdysfunction has often been studied in animalmodels of PH, such as themonocrotaline rat model. 6 Although these models have proven to be valuable, they have two important disadvantages: direct therapeutic effects on the RV cannot be distinguished from (afterload- reducing) effects on the pulmonary vasculature and the used ‘hits’ necessary to induce PH may affect the RV. 7 The use of a pulmonary artery banding (PAB) to inflict chronic pressure load on the RV circumvents these limitations. However, it has been debatedwhether the phenotype of the chronic PAB model represents compensated adaptation instead of RV failure. 8–10 Heart failure is defined as the inability to meet the metabolic requirements of the tissues of the body. Heart failure is not an entity as such but a continuum of disease severity, graded according to the NYHA class. RV failure is defined similarly, but the clinical signs and symptoms differ from those in LV failure. The cardinal clinical characteristics of RV failure are fluid retention (presenting as peripheral edema, effusion, ascites) and low cardiac output (evident in decreased exercise tolerance, fatigue, dyspnea and poor peripheral circulation). 11,12 Previously described PAB models showed features of chronic adaptation and mild RV dysfunction, e.g. RV dilatation, reduced TAPSE and hypertrophy, 8,9,13 but whether these represent the clinical phenotype of RV failure is unclear because the studies with hemodynamical analyses lack data on clinical symptoms of RVF 14,15 and conversely, the studies reporting on the clinical phenotype of RV failure lack (extensive) hemodynamical data. 8,10 The clinical phenotype of RV failure consists of signs and symptoms as dyspnea at rest, hepatomegaly, ascites, pleural effusion and mortality. 5,12 In the current study we aimed to characterize a phenotype of clinical RVF in rats with a tighter PAB (1.1 mm) than described before, 8,9,16,17 using clinical symptoms in