Effects of genetic background, sex, and age on murine atrial electrophysiology

TY - JOUR

T1 - Effects of genetic background, sex, and age on murine atrial electrophysiology

AU - Obergassel, Julius

AU - O'Reilly, Molly

AU - Sommerfeld, Laura C

AU - Kabir, S Nashitha

AU - O'Shea, Christopher

AU - Syeda, Fahima

AU - Eckardt, Lars

AU - Kirchhof, Paulus

AU - Fabritz, Larissa

N1 - Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

PY - 2021/6/7

Y1 - 2021/6/7

N2 - AIMS: Genetically altered mice are powerful models to investigate mechanisms of atrial arrhythmias, but normal ranges for murine atrial electrophysiology have not been robustly characterized.METHODS AND RESULTS: We analyzed results from 221 electrophysiological (EP) studies in isolated, Langendorff-perfused hearts of wildtype mice (114 female, 107 male) from 2.5 to 17.7 months (mean 7 months) with different genetic backgrounds (C57BL/6, FVB/N, MF1, 129/Sv, Swiss agouti). Left atrial monophasic action potential duration (LA-APD), interatrial activation time (IA-AT), and atrial effective refractory period (ERP) were summarized at different pacing cycle lengths (PCLs). Factors influencing atrial electrophysiology including genetic background, sex, and age were determined. LA-APD70 was 18 ± 0.5 ms, atrial ERP was 27 ± 0.8 ms, and IA-AT was 17 ± 0.5 ms at 100 ms PCL. LA-APD was longer with longer PCL (+17% from 80 to 120 ms PCL for APD70), while IA-AT decreased (-7% from 80 to 120 ms PCL). Female sex was associated with longer ERP (+14% vs. males). Genetic background influenced atrial electrophysiology: LA-APD70 (-20% vs. average) and atrial ERP (-25% vs. average) were shorter in Swiss agouti background compared to others. LA-APD70 (+25% vs. average) and IA-AT (+44% vs. average) were longer in 129/Sv mice. Atrial ERP was longer in FVB/N (+34% vs. average) and in younger experimental groups below 6 months of age.CONCLUSION: This work defines normal ranges for murine atrial EP parameters. Genetic background has a profound effect on these parameters, at least of the magnitude as those of sex and age. These results can inform the experimental design and interpretation of murine atrial electrophysiology.

AB - AIMS: Genetically altered mice are powerful models to investigate mechanisms of atrial arrhythmias, but normal ranges for murine atrial electrophysiology have not been robustly characterized.METHODS AND RESULTS: We analyzed results from 221 electrophysiological (EP) studies in isolated, Langendorff-perfused hearts of wildtype mice (114 female, 107 male) from 2.5 to 17.7 months (mean 7 months) with different genetic backgrounds (C57BL/6, FVB/N, MF1, 129/Sv, Swiss agouti). Left atrial monophasic action potential duration (LA-APD), interatrial activation time (IA-AT), and atrial effective refractory period (ERP) were summarized at different pacing cycle lengths (PCLs). Factors influencing atrial electrophysiology including genetic background, sex, and age were determined. LA-APD70 was 18 ± 0.5 ms, atrial ERP was 27 ± 0.8 ms, and IA-AT was 17 ± 0.5 ms at 100 ms PCL. LA-APD was longer with longer PCL (+17% from 80 to 120 ms PCL for APD70), while IA-AT decreased (-7% from 80 to 120 ms PCL). Female sex was associated with longer ERP (+14% vs. males). Genetic background influenced atrial electrophysiology: LA-APD70 (-20% vs. average) and atrial ERP (-25% vs. average) were shorter in Swiss agouti background compared to others. LA-APD70 (+25% vs. average) and IA-AT (+44% vs. average) were longer in 129/Sv mice. Atrial ERP was longer in FVB/N (+34% vs. average) and in younger experimental groups below 6 months of age.CONCLUSION: This work defines normal ranges for murine atrial EP parameters. Genetic background has a profound effect on these parameters, at least of the magnitude as those of sex and age. These results can inform the experimental design and interpretation of murine atrial electrophysiology.

U2 - 10.1093/europace/euaa369

DO - 10.1093/europace/euaa369

M3 - SCORING: Journal article

C2 - 33462602

VL - 23

SP - 958

EP - 969

JO - EUROPACE

JF - EUROPACE

SN - 1099-5129

IS - 6

ER -