Author:
Oestereicher Manuela A.,Wotton Janine M.,Ayabe Shinya,Bou About Ghina,Cheng Tsz Kwan,Choi Jae-Hoon,Clary Dave,Dew Emily M.,Elfertak Lahcen,Guimond Alain,Haseli Mashhadi Hamed,Heaney Jason D.,Kelsey Lois,Keskivali-Bond Piia,Lopez Gomez Federico,Marschall Susan,McFarland Michael,Meziane Hamid,Munoz Fuentes Violeta,Nam Ki-Hoan,Nichtová Zuzana,Pimm Dale,Bower Lynette,Prochazka Jan,Rozman Jan,Santos Luis,Stewart Michelle,Tanaka Nobuhiko,Ward Christopher S.,Willett Amelia M. E.,Wilson Robert,Braun Robert E.,Dickinson Mary E.,Flenniken Ann M.,Herault Yann,Lloyd K. C. Kent,Mallon Ann-Marie,McKerlie Colin,Murray Stephen A.,Nutter Lauryl M. J.,Sedlacek Radislav,Seong Je Kyung,Sorg Tania,Tamura Masaru,Wells Sara,Schneltzer Elida,Fuchs Helmut,Gailus-Durner Valerie,Hrabe de Angelis Martin,White Jacqueline K.,Spielmann Nadine
Abstract
AbstractReference ranges provide a powerful tool for diagnostic decision-making in clinical medicine and are enormously valuable for understanding normality in pre-clinical scientific research that uses in vivo models. As yet, there are no published reference ranges for electrocardiography (ECG) in the laboratory mouse. The first mouse-specific reference ranges for the assessment of electrical conduction are reported herein generated from an ECG dataset of unprecedented scale. International Mouse Phenotyping Consortium data from over 26,000 conscious or anesthetized C57BL/6N wildtype control mice were stratified by sex and age to develop robust ECG reference ranges. Interesting findings include that heart rate and key elements from the ECG waveform (RR-, PR-, ST-, QT-interval, QT corrected, and QRS complex) demonstrate minimal sexual dimorphism. As expected, anesthesia induces a decrease in heart rate and was shown for both inhalation (isoflurane) and injectable (tribromoethanol) anesthesia. In the absence of pharmacological, environmental, or genetic challenges, we did not observe major age-related ECG changes in C57BL/6N-inbred mice as the differences in the reference ranges of 12-week-old compared to 62-week-old mice were negligible. The generalizability of the C57BL/6N substrain reference ranges was demonstrated by comparison with ECG data from a wide range of non-IMPC studies. The close overlap in data from a wide range of mouse strains suggests that the C57BL/6N-based reference ranges can be used as a robust and comprehensive indicator of normality. We report a unique ECG reference resource of fundamental importance for any experimental study of cardiac function in mice.
Funder
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
Publisher
Springer Science and Business Media LLC