We recorded ECGs in 10 males and 10 females each of C57BL/6, 129/Sv, and FVB/N mice, three inbred strains commonly used to model human diseases. A representative ECG recording from an adult male C57BL/6 mouse is shown in Fig. . Since the mice are conscious, baseline artifact and noise are apparent in the unfiltered signals. Yet, the P-waves and T-waves are discernible by eye and interpretable by the software algorithmic processing of the signal digitized at 2500 samples per second. Analyses of the digitized signals via e-MOUSE™ demonstrated significantly faster heart rates in C57BL/6 female mice than in males (741 ± 2 bpm vs. 692 ± 5 bpm, P < 0.05, n = 10) and shorter QRS duration (7.5 ± 0.2 ms vs. 8.1 ± 0.2 ms, P < 0.05). Table summarizes results in 129/Sv mice (10 males and 10 females), again demonstrating faster heart rate and shorter QRS duration and QT interval in female mice than in age-matched males. Rate corrected QT (QTc) in male 129/Sv mice was significantly longer than in females (66.7 ± 1.9 ms vs. 58.4 ± 1.6 ms, P < 0.05). Gender differences in heart rate were also apparent in the FVB/N strain [736 ± 5 bpm in males (n = 10) vs. 706 ± 7 bpm in females (n = 10), P < 0.05].
Electrocardiogram from a conscious adult male C57BL/6 mouse at baseline, with indication of ECG parameters.
Electrocardiographic parameters in male and female 129/Sv, C57BL/6, and FVB conscious mice.
Reducing the spacing of the electrodes allowed us to record ECGs in 6-day and again in 12-day old nursling C57BL/6 mice (8 males and 5 females) and return them to their mother. The ECG from a 6-day-old C57BL/6 nursling female is shown in Fig. . Heart rate variability in neonates was significantly less than in adults (2.5 ± 0.4 bpm vs. 21 ± 2 bpm, P < 0.05). Heart rate in nursling females was significantly slower than in adult females (655 ± 6 bpm vs. 741 ± 2 bpm, P < 0.05). Interestingly, the gender differences in heart rate we observed in adult mice were absent in 6-day old and 12-day old neonates. Upon weaning (21 days old), however, gender differences in heart rate became apparent [697 ± 14 bpm in males (n = 5) vs. 750 ± 8 bpm in females (n = 3), P < 0.05].
Electrocardiogram from a conscious neonate (6 days old) female C57BL/6 mouse. Heart rate variability in neonates was significantly less than in adult mice.
The acute increase in heart rate within the first minutes following one intraperitoneal injection of the β-adrenergic agonist isoproterenol (2.5 μg/g) was significantly less in female compared to male C57BL/6 adult mice (+5 ± 2% females vs. +12 ± 2% males, P < 0.05, n = 5 for each group). Saline injection had no effect on heart rate. After 3 days of repeated isoproterenol injection (2.5 μg/g, once at 9AM and once at 9PM), heart rate in males prior to the 6th injection was significantly reduced compared to control heart rate in males prior to the 1st injection, whereas the heart rate in females did not change. Both male and female mice exhibited significant acute increases in heart rate (+27 ± 6% males and +22 ± 3% females) after the 6th injection of the drug on day 3 (P < 0.05 compared to % increases following 1st injection on day 1). Fig. illustrates significant electrocardiographic alterations immediately after the 1st administration of isoproterenol on day 1 in a C57BL/6 male mouse. ST segment depression, suggestive of acute subendocardial ischemia, was consistently observed in C57BL/6 male mice but not in all female mice immediately following administration of isoproterenol. Heart weight in males and females treated with isoproterenol for 3 days was significantly increased (16%) compared to hearts from mice treated with saline for 3 days (P < 0.05).
Electrocardiogram from the C57BL/6 male mouse of Fig. recorded immediately after an intraperitoneal injection of 2.5 μg/g isoproterenol on day 1, showing ST segment depression suggestive of acute subendocardial ischemia.