Standard protocol for electrocardiogram test

ECGs are recorded using a non-invasive AnonyMOUSE recording platform from Mouse Specifics, Inc. (Boston, MA) according to the method of Chu et al. [Chu 2001] and described in detail in the "Rapid Screening of Electrocardiograms" project by Hampton et al. on the Mouse Phenome Database Web site. Mice are removed from their cages and placed on the recording platform containing 3 gel-coated electrodes embedded in the floor. Each mouse is allowed to acclimatize for 10 minutes prior to collection of ECG waveform data. At the end of the acclimatization period, mice are positioned so that both hind paws and the right front paw each came into contact with an electrode. Positioning is accomplished by gently moving the mouse and/or the paws with a cotton-tipped swab. The electrodes are connected to an amplifier by a shielded 3-electrode lead set. Electrical signals are digitized with 16-bit precision at a sampling rate of 2000 samples/second. Data records containing at least 12 consecutive ECG waveforms are used for analyses. Data is sent to the Mouse Specifics, Inc. Web site using standard file-transfer protocols for analyses.

ECG waveforms are analyzed using e-MOUSE, an internet-based analysis portal (see Chu et al. 2002 and “Rapid Screening of Electrocardiograms” MPD project by Hampton et al. for complete details). Briefly, the e-MOUSE software uses a peak detection algorithm to find the peaks of the R-waves and to calculate heart rate (HR). The software plots its interpretation of P,Q,R,S, and T for each beat, and the mean of the ECG time intervals for each set of waveforms is calculated. Heart rate variability (HRV) is calculated as the standard deviation of all R-R intervals for each set of ECG signals, and the coefficient of variance (CV, %) is calculated as the ratio of mean HRV to mean HR. QT interval is calculated by using the end of the T-wave of each signal, defined as the point where the signal returns to the isoelectric line (the mean voltage between the preceding P-wave and QRS interval), and includes the inverted and/or biphasic portions of the T Wave [Mitchell]. QT intervals are rate-corrected (QTc) according to the equation described by Mitchell et al. [Mitchell].

Customized options

  • Testing before and after compound administration
  • Repeated measurements over time to detect developmental and age-related changes 

References

Bestetti RB, Oliveira JS. The surface electrocardiogram: a simple and reliable method for detecting overt and latent heart disease in rats. Braz J Med Biol Res. 1990;23:1213-22 [PubMed: 2136553].

Braun A, Trigatti BL, Post MJ, Sato K, Simons M, Edelberg JM, Rosenberg RD, Schrenzel M, Krieger M. Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein E-deficient mice. Circ Res. 2002;90:270-6 [PubMed: 11861414].

Chu V, Otero JM, Lopez O, Morgan JP, Amende I, Hampton TG. Method for non-invasively recording electrocardiograms in conscious mice. BMC Physiol. 2001;1(1):6 [PubMed: 11476671].

Chu, V, Otero, J, Lopez, O, Sullivan, MF, Morgan, JP, Amende, I, Hampton, TG. Electrocardiographic findings in mdx mice: A cardiac phenotype of Duchenne muscular dystrophy. Muscle Nerve 2002;26:513-519 [PubMed: 12362417].

Desai KH, Sato R, Schauble E, Barsh GS, Kobilka BK, Bernstein D. Cardiovascular indexes in the mouse at rest and with exercise: new tools to study models of cardiac disease. Am J Physiol. 1997;272:H1053-61 [PubMed: 9124413].

Kirchhoff S, Nelles E, Hagendorff A, Kruger O, Traub O, Willecke K. Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice. Curr Biol. 1998;8:299-302 [PubMed: 9501070].

Mitchell GF, Jeron A, Koren G. Measurement of heart rate and Q-T interval in the conscious mouse. Am J Physiol. 1998;274:H747-51 [PubMed: 9530184]. 

Wang L, Swirp S, Duff H. Age-dependent response of the electrocardiogram to K(+) channel blockers in mice. Am J Physiol. 2000;278:C73-80 [PubMed: 10644514].