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Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated which anaesthetic, ketamine\/xylazine or isoflurane, could be used to reveal diastolic dysfunction in HFpEF-diseased obese ZSF1 rats by echocardiography. First, diastolic dysfunction was confirmed by pressure-volume loops in obese compared to lean control ZSF1 rats. In echocardiography, ketamine\/xylazine, unlike isoflurane, was able to demonstrate impaired relaxation in obese ZSF1 rats, as reflected by impaired early (E) and late (A) filling peak velocities, decreased E\/A ratio, and a prolonged deceleration and isovolumic relaxation time. Interestingly, ketamine\/xylazine induced a wider separation of both tissue and pulsed wave Doppler-derived echocardiographic waves required for diastolic dysfunction diagnosis, potentially by reducing the heart rate (HR), while isoflurane resulted in merged waves. To assess whether HR-lowering alone explained the differences between the anaesthetics, echocardiography measurements under isoflurane with and without the HR-lowering drug ivabradine were compared. However, diastolic dysfunction could not be diagnosed in ivabradine-treated obese ZSF1 rats. In summary, ketamine\/xylazine compared to isoflurane is the anaesthetic of choice to detect diastolic dysfunction by echocardiography in rodent HFpEF, which was only partly mediated by HR-lowering.<\/jats:p>","DOI":"10.1038\/s41598-020-72924-5","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T10:05:36Z","timestamp":1600941936000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The effect of different anaesthetics on echocardiographic evaluation of diastolic dysfunction in a heart failure with preserved ejection fraction model"],"prefix":"10.1038","volume":"10","author":[{"given":"Ilona","family":"Cuijpers","sequence":"first","affiliation":[]},{"given":"Paolo","family":"Carai","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Mendes-Ferreira","sequence":"additional","affiliation":[]},{"given":"Steven J.","family":"Simmonds","sequence":"additional","affiliation":[]},{"given":"Paul","family":"Mulder","sequence":"additional","affiliation":[]},{"given":"Daniela","family":"Miranda-Silva","sequence":"additional","affiliation":[]},{"given":"Daria","family":"De Giorgio","sequence":"additional","affiliation":[]},{"given":"Peter","family":"Pokreisz","sequence":"additional","affiliation":[]},{"given":"Stephane","family":"Heymans","sequence":"additional","affiliation":[]},{"given":"Elizabeth A. 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