Key result
Ketamine/xylazine, unlike isoflurane, enabled the echocardiographic detection of diastolic dysfunction in a rodent model of heart failure with preserved ejection fraction.
Why the study?
Developing therapeutics for untreated HFpEF requires effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which depends on appropriate anaesthetics.
Does ketamine/xylazine compared to isoflurane improve the echocardiographic detection of diastolic dysfunction in a rat model of HFpEF?
Does ketamine/xylazine compared to isoflurane improve the echocardiographic detection of diastolic dysfunction in a rat model of HFpEF?
Answers are grounded in this paper and cite their sources.
Ketamine/xylazine is the preferred anesthetic over isoflurane for the echocardiographic evaluation of diastolic dysfunction in rodent models of HFpEF.
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.
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Cuijpers et al. (2020) studied Heart failure with preserved ejection fraction (HFpEF) animal model (n=48). Ketamine/xylazine vs. Isoflurane was evaluated on Echocardiographic detection of diastolic dysfunction (e.g., E/A ratio, E and A peak velocities). Ketamine/xylazine, unlike isoflurane, enabled the echocardiographic detection of diastolic dysfunction in a rodent model of heart failure with preserved ejection fraction.
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