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Diurnal Changes in Atrioventricular Conduction in Mice
Victor Chu, Ivo Amende, Ajit Kale*, Jose M. Otero,
Wade Thomas*, and Thomas G. Hampton;
Mouse Specifics, Inc. and *The CuraVita Corporation, Boston, MA. USA.
Web published: February 1, 2002
Abstract
Cardiac conduction abnormalities have been associated with defects in genes encoding for voltage-dependent ion channel proteins1 and connexins.2 Diurnal variation in atrioventricular (AV) conduction characteristics may be a factor in the risk for arrhythmogenesis.3 We sought to determine how PR interval duration might differ between genders and between the “waking” and “sleeping” hours in mice. We demonstrate, non-invasively, important gender and diurnal variation in AV conduction in conscious mice.
Methods
Figure 1.ECG in conscious male mouse at 02:00.
Adult Balb/C mice were obtained from The Jackson Laboratory. The AnonyMOUSETM ECG screening system was used to record ECGs.4 Neither anesthetic nor surgery was required. Data were acquired at 2kHz for at least 2 seconds to provide equivalent continuous recordings of 20 to 30 beats. e-MOUSETM was used to interpret the signals. PR interval duration was measured from the peak of the P wave.
Results
Diurnal AV conduction changes.
Male Balb/C
14:00 (n=6)
02:00 (n=6)
PR (ms)
27.1 ± 0.4
25.6 ± 0.3*
PR/RR
0.35 ± 0.01
0.32 ± 0.01*
Female Balb/C
14:00 (n=6)
02:00 (n=6)
PR (ms)
25.3 ± 0.4†
25.6 ± 0.4
PR/RR
0.31 ± 0.01†
0.29 ± 0.01†
*P<0.05 night vs. day.
†P<0.05 female vs. male.
Discussion
A representative ECG signal from an adult Balb/C male mouse recorded at 2am is shown in Figure 1. Even the small voltages associated with atrial depolarization are detectable and quantifiable with our non-invasive system. During the daytime, the less active hours for mice, the PR interval duration is faster in female Balb/C mice compared to males, consistent with the observations of faster heart rates in females observed in some strains.4 At nighttime, when the activity of these animals is nearly double5, PR interval duration decreased significantly in males, such that there was no difference between males and females in AV conduction velocity. Yet, PR/RR remained smaller in females at night. The diurnal variation we observed in mice is consistent with what has been observed in healthy humans.3 We demonstrate a non-invasive approach for evaluating atrioventricular conduction in conscious mice that may accelerate understanding and treatment of cardiac arrhythmias.
References
Casimiro, M.C. et al. 2001. PNAS. 98:2526-2531.
Kirchoff, S. et al. 1998. Current Biology. 8:299-302.
Dilaveris, P.E. et al. 2001. Ann. Noninvasive Electrocardiol. 6:92-97.