Tailored anesthesia protocols for echo-based HFpEF phenotyping in C57BL6/N mice.

Echocardiographic evaluation of diastolic function in murine heart failure with preserved ejection fraction (HFpEF) models remains challenging due to insufficient temporal resolution of current high-frequency Doppler probes at heart rates beyond 450 beats/min. Aiming to optimize anesthesia for diastolic assessment in mice, we compared standard isoflurane sedation with a combination of isoflurane and either of the negative chronotropic substances medetomidine or esmolol. Both combined anesthetic regimens preserved Doppler measurement accuracy while resulting in lower heart rates, better discernibility of separate Doppler velocity waves, and shorter examination times. However, the combination of isoflurane and medetomidine showed a superior safety profile, preservation of systolic function, and higher interrater reliability, recommending itself as a refined anesthetic protocol for echo-based HFpEF phenotyping in C57BL6/N mice.NEW & NOTEWORTHY Combining isoflurane with medetomidine for anesthesia in murine diastolic function echocardiography leads to lower heart rates with better discernibility of separate waves in Doppler velocity curves while preserving measurement accuracy and systolic function. This results in higher interrater reliability and shorter examination times, improving reproducibility and reducing stress for the animal.