Development, characterization, maintenance and breeding of DSSLepR rats - a new model for heart failure with preserved ejection fraction (HFpEF)

Heart failure (HF) is a serious condition with high morbidity and mortality. About half of patients with HF suffer from HF with preserved ejection fraction (HFpEF), for which there exists no pharmacological treatment. Research on HFpEF has been hampered by the lack of good animal models. The DSSLepR rats were recently described as a new animal model of HFpEF (Murase et al., 2012, in attachment). The purpose of this project is to use the DSSLepR animal model to characterize changes that occur in HFpEF and for production of rats for use in other projects aimed at developing treatment for HFpEF. The expected adverse effects on the animal would be development of heart failure, whereas the benefit to the society would be knowledge on HFpEF development and potential new treatment modalities. A total of 1632 animals over 4 years will be included in the project including littermate controls that do not develop HFpEF and breeding of animals to be used in other projects with separate applications. There exists no adequate non-biological models for HFpEF and multiple factors will be measured in both intact animal and isolated muscle strips and isolated cells to reduce the number of animals needed. Experiments are refined to minimize pain during necessary procedures to study cardiac function. The current protocol is for the development, characterisation and maintenance of this new HFpEF rat model, including production of rats for use in other projects.