Heart Rate and Electrocardiography Monitoring in Mice

David Ho1, Xin Zhao1, Shumin Gao1, Chull Hong1, Dorothy E. Vatner1, Stephen F. Vatner1

1 The University of Medicine & Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey
Publication Name:  Current Protocols in Mouse Biology
Unit Number:   
DOI:  10.1002/9780470942390.mo100159
Online Posting Date:  March, 2011
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Abstract

The majority of current cardiovascular research involves studies in genetically engineered mouse models. The measurement of heart rate is central to understanding cardiovascular control under normal conditions, with altered autonomic tone and with superimposed stress, or in disease states, both in wild‐type mice and in those with altered genes. Electrocardiography (ECG) is the “gold standard,” using either hard‐wired or telemetry transmission. In addition, heart rate is measured or monitored from the frequency of the arterial pressure pulse or cardiac contraction, or by pulse oximetry. For each of these techniques, discussions of materials and methods, as well as advantages and limitations, are covered. However, direct ECG monitoring alone will determine not only the precise heart rates but also whether the cardiac rhythm is normal or not. Curr. Protoc. Mouse Biol. 1:123‐139. © 2011 by John Wiley & Sons, Inc.

Keywords: heart‐rate monitoring; mice; electrocardiography ECG

     
 
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Table of Contents

  • Introduction
  • Basic Protocol 1: Noninvasive ECG System
  • Basic Protocol 2: Tethered ECG System
  • Basic Protocol 3: Implanted ECG Telemetry System
  • Basic Protocol 4: Pulse Oximetry
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Noninvasive ECG System

  Materials
  • Mice
  • AnonyMouse ECG screening system (Mouse Specifics, Inc., http://www.mousespecifics.com/)
  • Cotton‐tipped sticks
  • Gel‐coated ECG electrodes
  • Amplifier (HP78901A, Hewlett‐Packard)
  • Shielded 3 electrode lead set (M1605A Snap, Hewlett‐Packard)
  • Recording computer
  • eMouse Internet‐based wave‐analysis portal (http://www.mousespecifics.com/)

Basic Protocol 2: Tethered ECG System

  Materials
  • Mice
  • Anesthesia (see Table 10.1.5900 and annotation to step 2, below)
  • Insulated wire leads (AWG size 36)
  • Surgical instruments
  • Suture: 6‐0 nylon for ECG lead fixation and skin closure
  • Tether system including a harness (or jacket) (Instech, http://www.instechlabs.com/)
  • Swivel system (Instech)
  • ECG system including:
    • Amplifier box (Gould Instrument Systems, item no. 11‐4123‐09)
    • Amplifier (Gould Instrument Systems, item no. Amp6600)
    • Tektronix TDS 1002 Oscilloscope (Tektronix, part no. 93K5765)
  • Small protective plastic tube (made by cutting a 4‐mm section from the mid‐portion of a plastic transfer pipet; VWR, cat. no. 3‐711‐7)
  • Restraint box with ceiling hole (Braintree Scientific, cat. no. 500M‐C)

Basic Protocol 3: Implanted ECG Telemetry System

  Materials
  • Mice
  • Anesthesia (see Table 10.1.5900 and annotation to step 2, below)
  • Surgical instruments
  • Suture: 5‐0 nylon for transmitter fixation to skin; 7‐0 silk for telemetry wire fixation
  • Telemetry transmitter device (ETA F‐10 or EA‐F20; Data Sciences International)
  • Magnet (any commercially available magnet can be used)
  • Anesthesia (see Table 10.1.5900 and step 1)

Basic Protocol 4: Pulse Oximetry

  Materials
  • Mice
  • MouseOx pulse oximeter with CollarClips, ThroatClips, and Thigh Sensors (Starr Life Sciences Corp., http://www.starrlifesciences.com/)
  • Hair clippers
  • MouseOx software (Starr Life Sciences Corp., http://www.starrlifesciences.com)
  • STARR‐Link analog output module (Starr Life Sciences Corp.)
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Figures

  •   FigureFigure 1. Calculation of heart rate (HR) (panels C and D) by counting the number of aortic pressure waves (AOP) (panels A and B) in a sedated mouse. The arrows represent the injections of phenylephrine (PE) to increase pressure and sodium nitroprusside (SNP) to decrease pressure. The arterial baroreceptor reflex reduces heart rate with pressure elevation and decreases heart rate when pressure falls.
  •   FigureFigure 2. Sample of telemetry ECG simultaneous recording of three mice. A typical mouse ECG contains a P wave, followed by the QRS complex and the T wave. The distance between two consecutive R waves is termed RR interval and represents the time it takes for one beat, and the PR interval represents the time for electrical conduction from the atria to the ventricle. The plus (+) on the ECG represents the computer‐identified R wave.
  •   FigureFigure 3. An illustration of tethered ECG insertion and recording of mouse heart rate. The ECG leads are labeled and subcutaneously tunneled onto the back of the mouse in positions of the four limbs. Mice are housed individually during the recording process with the leads connected to the tether system for data acquisition.
  •   FigureFigure 4. Circadian variation of heart rate in transgenic mice with cardiac specific overexpression of Gsα (TG) and wild‐type mice. Heart rates were obtained from ECGs recorded using a telemetric system in conscious unrestrained mice. The inset shows the difference in heart rate variability over a 1‐hr period in one TG and one wild‐type control mouse. Figure and legend used and modified with permission (Uechi et al., ).
  •   FigureFigure 5. An illustration of the telemetry unit with the anchoring sutures in place. In general two to three anchoring sutures are used to fix the telemetry unit to the chest wall of the mice.
  •   FigureFigure 6. Sample of ECG recording using a telemetric system for a free‐ranging transgenic mouse overexpressing Gsα (top) and a wild‐type control mouse (bottom). The telemetric implant is shown in the abdominal cavity of the mouse. The recorded heart rates were higher in the transgenic mice. The darker lines at the right of the ECG tracing shown are the compressed ECG tracing printed at a slow paper speed. Figure and legend used and modified with permission (Uechi et al., ).

Videos

Literature Cited

Literature Cited
   Appel, M.L., Berger, R.D., Saul, J.P., Smith, J.M., and Cohen, R.J. 1989. Beat to beat variability in cardiovascular variables: Noise or music? J. Am. Coll. Cardiol. 14:1139‐1148.
   Bigger, J.T. Jr., Fleiss, J.L., Steinman, R.C., Rolnitzky, L.M., Kleiger, R.E., and Rottman, J.N. 1992. Frequency domain measures of heart period variability and mortality after myocardial infarction. Circulation 85:164‐171.
   D'Angelo, D.D., Sakata, Y., Lorenz, J.N., Boivin, G.P., Walsh, R.A., Liggett, S.B., and Dorn, G.W. 2nd. 1997. Transgenic Galphaq overexpression induces cardiac contractile failure in mice. Proc. Natl. Acad. Sci. U.S.A. 94:8121‐8126.
   de Bruyne, M.C., Hoes, A.W., Kors, J.A., Hofman, A., van Bemmel, J.H., and Grobbee, D.E. 1999. Prolonged QT interval predicts cardiac and all‐cause mortality in the elderly. The Rotterdam Study. Eur. Heart J. 20:278‐284.
   Erhardt, W., Hebestedt, A., Aschenbrenner, G., Pichotka, B., and Blumel, G. 1984. A comparative study with various anesthetics in mice (pentobarbitone, ketamine‐xylazine, carfentanyl‐etomidate). Res. Exp. Med. (Berl.) 184:159‐169.
   Gao, S., Ho, D., Vatner, D.E., and Vatner, S.F. 2011. Echocardiography in mice. Curr. Protoc. Mouse Biol. 1:71‐83.
   Gross, V. and Luft, F.C. 2003. Exercising restraint in measuring blood pressure in conscious mice. Hypertension 41:879‐881.
   Iyriboz, Y., Powers, S., Morrow, J., Ayers, D., and Landry, G. 1991. Accuracy of pulse oximeters in estimating heart rate at rest and during exercise. Br. J. Sports Med. 25:162‐164.
   Kleiger, R.E., Miller, J.P., Bigger, J.T. Jr., and Moss, A.J. 1987. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am. J. Cardiol. 59:256‐262.
   Kovoor, P., Wickman, K., Maguire, C.T., Pu, W., Gehrmann, J., Berul, C.I., and Clapham, D.E. 2001. Evaluation of the role of I(KACh) in atrial fibrillation using a mouse knockout model. J. Am. Coll. Cardiol. 37:2136‐2143.
   Kramer, K., van Acker, S.A., Voss, H.P., Grimbergen, J.A., van der Vijgh, W.J., and Bast, A. 1993. Use of telemetry to record electrocardiogram and heart rate in freely moving mice. J. Pharmacol. Toxicol. Methods 30:209‐215.
   Kurtz, T.W., Griffin, K.A., Bidani, A.K., Davisson, R.L., and Hall, J.E. 2005a. Recommendations for blood pressure measurement in animals: Summary of an AHA scientific statement from the Council on High Blood Pressure Research, Professional and Public Education Subcommittee. Arterioscler. Thromb. Vasc. Biol. 25:478‐479.
   Kurtz, T.W., Griffin, K.A., Bidani, A.K., Davisson, R.L., and Hall, J.E. 2005b. Recommendations for blood pressure measurement in humans and experimental animals. Part 2: Blood pressure measurement in experimental animals: A statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Arterioscler. Thromb. Vasc. Biol. 25:e22‐e33.
   Lin, M., Harden, S.W., Li, L., Wurster, R.D., and Chen, Z. 2010. Impairment of baroreflex control of heart rate in conscious transgenic mice of type 1 diabetes (OVE26). Auton. Neurosci. 152:67‐74.
   Lorenz, J.N. 2002. A practical guide to evaluating cardiovascular, renal, and pulmonary function in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282:R1565‐R1582.
   Mitchell, G.F., Jeron, A., and Koren, G. 1998. Measurement of heart rate and Q‐T interval in the conscious mouse. Am. J. Physiol. 274:H747‐H751.
   Montanez, A., Ruskin, J.N., Hebert, P.R., Lamas, G.A., and Hennekens, C.H. 2004. Prolonged QTc interval and risks of total and cardiovascular mortality and sudden death in the general population: A review and qualitative overview of the prospective cohort studies. Arch. Intern. Med. 164:943‐948.
   Odashima, M., Usui, S., Takagi, H., Hong, C., Liu, J., Yokota, M., and Sadoshima, J. 2007. Inhibition of endogenous Mst1 prevents apoptosis and cardiac dysfunction without affecting cardiac hypertrophy after myocardial infarction. Circ. Res. 100:1344‐1352.
   Peter, P.S., Brady, J.E., Yan, L., Chen, W., Engelhardt, S., Wang, Y., Sadoshima, J., Vatner, S.F., and Vatner, D.E. 2007. Inhibition of p38 alpha MAPK rescues cardiomyopathy induced by overexpressed beta 2‐adrenergic receptor, but not beta 1‐adrenergic receptor. J. Clin. Invest. 117:1335‐1343.
   Rivera‐Ruiz, M., Cajavilca, C., and Varon, J. 2008. Einthoven's string galvanometer: The first electrocardiograph. Tex. Heart Inst. J. 35:174‐178.
   Sandercock, G.R. and Brodie, D.A. 2006. The role of heart rate variability in prognosis for different modes of death in chronic heart failure. Pacing Clin. Electrophysiol. 29:892‐904.
   Stypmann, J. 2007. Doppler ultrasound in mice. Echocardiography 24:97‐112.
   Uechi, M., Asai, K., Osaka, M., Smith, A., Sato, N., Wagner, T.E., Ishikawa, Y., Hayakawa, H., Vatner, D.E., Shannon, R.P., Homcy, C.J., and Vatner, S.F. 1998a. Depressed heart rate variability and arterial baroreflex in conscious transgenic mice with overexpression of cardiac Gsalpha. Circ. Res. 82:416‐423.
   Uechi, M., Uechi, H., Nakayama, T., Wakao, Y., Ogasawara, T., Takase, K., and Takahashi, M. 1998b. The circadian variation of urinary N‐acetyl‐beta‐d‐glucosaminidase and gamma‐glutamyl transpeptidase in clinically healthy cats. J. Vet. Med. Sci. 60:1033‐1034.
   Vatner, S.F. and Braunwald, E. 1975. Cardiovascular control mechanisms in the conscious state. N. Engl. J. Med. 293:970‐976.
   Vatner, S.F., Takagi, G., Asai, K., and Shannon, R.P. 2002. Cardiovascular physiology in mice: Conscious measurements and effects of anesthesia. In Cardiovascular Physiology in the Genetically Engineered Mouse (B.D. Hoit, ed.) pp. 257‐275. Kluwer Academic Publishers, New York.
   Xu, Q., Ming, Z., Dart, A.M., and Du, X.J. 2007. Optimizing dosage of ketamine and xylazine in murine echocardiography. Clin. Exp. Pharmacol. Physiol. 34:499‐507.
   Yan, L., Vatner, D.E., O'Connor, J.P., Ivessa, A., Ge, H., Chen, W., Hirotani, S., Ishikawa, Y., Sadoshima, J., and Vatner, S.F. 2007. Type 5 adenylyl cyclase disruption increases longevity and protects against stress. Cell 130:247‐258.
   Yang, X.P., Liu, Y.H., Rhaleb, N.E., Kurihara, N., Kim, H.E., and Carretero, O.A. 1999. Echocardiographic assessment of cardiac function in conscious and anesthetized mice. Am. J. Physiol. 277:H1967‐H1974.
   Zhao, X., Ho, D., Gao, S., Hong, C., Vatner, D.E., and Vatner, S.F. 2011. Arterial pressure monitoring in mice. Curr. Protoc. Mouse Biol. 1:105‐122.
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