Anne-Marie Koop

202 after operation, whereas the desired phenotype will not be achieved when the constriction is not tight enough. However, the use of mice has advantages compared to other animals, because of the excellent genetic modification possibilities (i.e., transgenic or knockout models) and fast breeding. This is of added value in the study of diseases and in exploring the contribution of molecular and (epi-) genetic factors. Animal study designs are shifting towards the investigation of temporal changes duringdisease. 2,3,8,13,21 Forsuchstudies, noninvasivemodalities arenecessary, because serial assessments can be performed. Alternatives to CMR in the assessment of cardiac remodelling could be (1) tissue characterization using histopathology, with multiple animals being sacrificed at different time points, (2) invasive functional assessment by pressure-volume analysis, or (3) echocardiography, which allows the researcher to identify cardiac hypertrophy or dilatation noninvasively within the same animal serially. CMR has two major advantages in assessment of the RV: (1) CMR is a noninvasive modality, enabling serial measurements in one animal, hereby contributing to reducing animal numbers needed for studies, and (2) CMR does not rely on a particular geometric shape and visualizes three-dimensionally. CMR- derived RV volumes and function measurements have been shown to be accurate and are considered to be the noninvasive golden standard in different cardiac entities in humans, 42-45 but had not yet been translated to a CMR protocol for mice with RV pressure overload. Many models of PAB are described in the literature, but with high heterogeneity in methods of assessing hemodynamic effects and RV function and adaptation. This protocol outlines the procedure of PAB in mice with validation of the model by measuring the PABgradient byechocardiographyand evaluating cardiac dimensions and functionwith CMR.While a protocol of CMR in animals subjected to PAB has been published for rats, this combination has not been described for mice until now. While rats are most commonly used for PH models, 8,12-16,22,24-31,46 mice are most often used for transgenic or knock-out studies and thereby contribute to our understanding of mechanisms inpressure-loadedRVfailure.Thisprotocolcouldformthebasisforfuture studies to unravel signaling pathways involved in the transition towards RV failure. PROTOCOL All experiments and animal care are conducted according to the Dutch Animal Experimental Act and conform to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health. The Animal Experiments Committee of the University of Groningen, the Netherlands, approved the current experimental protocol (permit number: 2014-041/3005).