TY - JOUR
T1 - The effect of different anaesthetics on echocardiographic evaluation of diastolic dysfunction in a heart failure with preserved ejection fraction model
AU - Cuijpers, Ilona
AU - Carai, Paolo
AU - Mendes-Ferreira, Pedro
AU - Simmonds, Steven J.
AU - Mulder, Paul
AU - Miranda-Silva, Daniela
AU - De Giorgio, Daria
AU - Pokreisz, Peter
AU - Heymans, Stephane
AU - Jones, Elizabeth A.
N1 - Funding Information:
This work was supported by European Research Area Networks on Cardiovascular Diseases (ERA-CVD) [LYMIT-DIS 2016] and Fonds Wetenschappelijk Onderzoek [1160718N, 9091018N, G0B5930N]. The research leading to these results has also received funding from the European Union Commission IMI2-CARDIATEAM [821508] and the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation [CVON She-PREDICTS, grant 2017-21] to SH. This project has also received funding from the European Union’s Horizon 2020 research and innovation program [848109] to E.A.V. Jones. We thank Dr. Nazha Hamdani and Árpád Kovács (Ruhr-Universität Bochum, Germany) for their helpful discussion, Prof. Dr. Bart de Geest (KU Leuven, Belgium) for the usage of the pressure-volume loop equipment, and Dr. Hanna Peacock (KU Leuven, Belgium) for proofreading the manuscript.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/9/24
Y1 - 2020/9/24
N2 - Heart failure with preserved ejection fraction (HFpEF) is currently untreated. 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.
AB - Heart failure with preserved ejection fraction (HFpEF) is currently untreated. 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.
U2 - 10.1038/s41598-020-72924-5
DO - 10.1038/s41598-020-72924-5
M3 - Article
C2 - 32973263
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 15701
ER -