Anne-Marie Koop

5 201 INTRODUCTION Patients with acquired and congenital cardiovascular diseases, including pulmonary hypertension (PH), are at risk of right ventricular (RV) dysfunction and failure. 1 RV adaptation as a result of increased pressure load is characterized by concentric hypertrophy in early stages and progressive dilatation in end-stage disease. Furthermore, it is associated with disorders in metabolism and the extracellular matrix, processes of inflammation and, eventually, RV failure. 2-6 Animal models have been developed to explore the underlying processes of the progression towards RV failure. However, optimization of models and adequate assessment of RV function and dimensions has been challenging. For noninvasive assessment of RV function and dimensions, cardiac magnetic resonance (CMR) imaging is the golden standard. This technique creates images of the beating heart by using a strong magnetic field and radiofrequency waves. CMR is available for humans, and for animals such as laboratory rodents. As the latter require higher spatial resolution due to the smaller size of the heart, the magnetic field required to provide adequate images must be higher, compared to humans. Multiple models mimicking RV pressure overload are available, including models of PH 7–17 a potent stimulus for pulmonary hypertension and right ventricular hypertrophy. When anesthetized rats adapted to chronic hypoxia spontaneously respired room air, their mean right intraventricular peak systolic pressure (RVSP and models of proximal RV pressure load. 2,3,10,18-23 The choice of either a model of PH or a model of proximal RV pressure load depends on the research question: the effect of an intervention on the pulmonary vasculature and therefore possibly RV afterload modulation (i.e., PH models), or the direct effect on the RV (i.e., proximal RV pressure load models). Several methods for experimental induction of PH are available, including use of monocrotaline (MCT), 12-14,16,22,24-26 MCT combined with an aortocaval shunt 9 , chronic hypoxia, 7,27-29 and the combination of a vascular endothelial growth factor receptor antagonist, Sugen 5416, with chronic hypoxia. 8,10,30,31 Such models represent progressive pulmonary models of proximal RV pressure load and are not targeted at the pulmonaryvasculature but induce a constant afterload by constriction of the pulmonary artery, with an accompanying increase of RV afterload. 2,3 This can be performed by a suture-banding (pulmonary artery banding, PAB) or a vascular clip around the pulmonary artery. PAB has been performed in several animal species, and cardiac dimensions and function have been studied in various ways, such as histology, transthoracic echocardiography (including speckle tracking), and heart catheterization. 2,32-40 PAB in small rodents, such as mice, is challenging. This is because subtle differences between the tightness of artery constriction have marked results on the degree of RV pressure load and subsequent functional status and survival. When the constriction is very tight, the animal will die during or shortly