Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Validation of Non-invasive Method for Electrocardiogram Recording in Mouse using Lead II

  • Kim, Myung Jun (Department of Biomedical Science, Graduate School, Kyung Hee University) ;
  • Lim, Ji Eun (Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University) ;
  • Oh, Bermseok (Department of Biomedical Science, Graduate School, Kyung Hee University)
  • Received : 2015.06.04
  • Accepted : 2015.09.30
  • Published : 2015.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Electrocardiogram measures the electric impulses generated by the heart during its cycle. Recently genome-wide association studies on electrocardiogram traits revealed many relevant genetic loci. Therefore, these findings need to be validated and investigated to determine the underlying mechanisms using mouse models. Invasive radiotelemetry has been widely used to record the electrocardiogram in mice because it has several advantages over non-invasive measurements. However, radiotelemetry is expensive and requires complicated surgery. On the other hand, a non-invasive method using 3 electrodes (one for earth) for lead II is easy to establish and allows for rapid measurement. In this study, eleven mice were measured with this non-invasive method and no statistical difference among them was found in any ECG measurements. In addition, repeat measurement in the same mouse was performed in 9 sets of experiment and the results indicated that non-invasive method was reliable for reproducibility. Further it was shown that measurements for 1, 5, 10, and 15 minutes were not different so that a short recording such as 5 minutes was enough to estimate the ECG values including heart rate. Further this method was validated by measuring the ECG of Balb/c and FVB that were previously shown to differ in ECG values by radiotelemetry. Significant differences were found in heart rate, PR interval and corrected QT interval between these mouse strains. This study partially proved that non-invasive method also could provide the accuracy and reproducibility. Based on these results, the non-invasive ECG recordings of lead II is recommended as a useful method for quick test in mouse model.

Keywords

References

  1. Bigger JT Jr, Fleiss JL, Steinman RC, Rolnitzky LM, Kleiger RE, Rottman JN. Frequency domain measures of heart period variability and mortality after myocardial infarction. Circulation. 1992. 85: 164-171. https://doi.org/10.1161/01.CIR.85.1.164
  2. Bruell JH, Daroczy AF, Hellerstein HK. Strain and sex differences in serum cholesterol levels of mice. Science. 1962. 135: 1071 -1072. https://doi.org/10.1126/science.135.3508.1071
  3. de Bruyne MC, Hoes AW, Kors JA, Hofman A, van Bemmel JH, Grobbee DE. Prolonged QT interval predicts cardiac and all-cause mortality in the elderly. The Rotterdam Study. Eur Heart J. 1999. 20: 278-284. https://doi.org/10.1053/euhj.1998.1276
  4. Erhardt W, Hebestedt A, Aschenbrenner G, Pichotka B, Blumel G. A comparative study with various anesthetics in mice (pentobarbitone, ketamine-xylazine, carfentanyl-etomidate). Res Exp Med (Berl). 1984. 184: 159-169. https://doi.org/10.1007/BF01852390
  5. Gao S, Ho D, Vatner DE, Vatner SF. Echocardiography in mice. Curr Protoc Mouse Biol. 2011. 1: 71-83.
  6. Goldbarg AN, Hellerstein HK, Bruell JH, Daroczy AF. Electrocardiogram of the normal mouse, Mus musculus: general considerations and genetic aspects. Cardiovasc Res. 1968. 2: 93-99. https://doi.org/10.1093/cvr/2.1.93
  7. Hart CY, Burnett JC Jr, Redfield MM. Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice. Am J Physiol Heart Circ Physiol. 2001. 281: H1938-H1945. https://doi.org/10.1152/ajpheart.2001.281.5.H1938
  8. Holm H, Gudbjartsson DF, Arnar DO, Thorleifsson G, Thorgeirsson G, Stefansdottir H, Gudjonsson SA, Jonasdottir A, Mathiesen EB, Njolstad I, Nyrnes A, Wilsgaard T, Hald EM, Hveem K, Stoltenberg C, Lochen ML, Kong A, Thorsteinsdottir U, Stefansson K. Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet. 2010. 42: 117-122. https://doi.org/10.1038/ng.511
  9. Hong KW, Lim JE, Kim JW, Tabara Y, Ueshima H, Miki T, Matsuda F, Cho YS, Kim Y, Oh B. Identification of three novel genetic variations associated with electrocardiographic traits (QRS duration and PR interval) in East Asians. Hum Mol Genet. 2014. 23: 6659-6667. https://doi.org/10.1093/hmg/ddu374
  10. Janse MJ, Opthof T, Kleber AG. Animal models of cardiac arrhythmias. Cardiovasc Res. 1998. 39: 165-177. https://doi.org/10.1016/S0008-6363(97)00313-1
  11. Kim JW, Hong KW, Go MJ, Kim SS, Tabara Y, Kita Y, Tanigawa T, Cho YS, Han BG, Oh B. A common variant in SLC8A1 is associated with the duration of the electrocardiographic QT interval. Am J Hum Genet. 2012. 91: 180-184. https://doi.org/10.1016/j.ajhg.2012.05.019
  12. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987. 59: 256-262. https://doi.org/10.1016/0002-9149(87)90795-8
  13. Lorenz JN. A practical guide to evaluating cardiovascular, renal, and pulmonary function in mice. Am J Physiol Regul Integr Comp Physiol. 2002. 282: R1565-R1582. https://doi.org/10.1152/ajpregu.00759.2001
  14. Mitchell GF, Jeron A, Koren G. Measurement of heart rate and Q-T interval in the conscious mouse. Am J Physiol. 1998. 274: H747-H751.
  15. Montanez A, Ruskin JN, Hebert PR, Lamas GA, Hennekens CH. 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. 2004. 164: 943-948. https://doi.org/10.1001/archinte.164.9.943
  16. Newton-Cheh C, Eijgelsheim M, Rice KM, de Bakker PI, Yin X, Estrada K, Bis JC, Marciante K, Rivadeneira F, Noseworthy PA, Sotoodehnia N, Smith NL, Rotter JI, Kors JA, Witteman JC, Hofman A, Heckbert SR, O'Donnell CJ, Uitterlinden AG, Psaty BM, Lumley T, Larson MG, Stricker BH. Common variants at ten loci influence QT interval duration in the QTGEN Study. Nat Genet. 2009. 41: 399-406. https://doi.org/10.1038/ng.364
  17. Odashima M, Usui S, Takagi H, Hong C, Liu J, Yokota M, Sadoshima J. Inhibition of endogenous Mst1 prevents apoptosis and cardiac dysfunction without affecting cardiac hypertrophy after myocardial infarction. Circ Res. 2007. 100: 1344-1352. https://doi.org/10.1161/01.RES.0000265846.23485.7a
  18. Pfeufer A, Sanna S, Arking DE, Muller M, Gateva V, Fuchsberger C, Ehret GB, Orru M, Pattaro C, Kottgen A, Perz S, Usala G, Barbalic M, Li M, Putz B, Scuteri A, Prineas RJ, Sinner MF, Gieger C, Najjar SS, Kao WH, Muhleisen TW, Dei M, Happle C, Mohlenkamp S, Crisponi L, Erbel R, Jockel KH, Naitza S, Steinbeck G, Marroni F, Hicks AA, Lakatta E, Muller-Myhsok B, Pramstaller PP, Wichmann HE, Schlessinger D, Boerwinkle E, Meitinger T, Uda M, Coresh J, Kaab S, Abecasis GR, Chakravarti A. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nat Genet. 2009. 41: 407-414. https://doi.org/10.1038/ng.362
  19. Pfeufer A, van Noord C, Marciante KD, Arking DE, Larson MG, Smith AV, Tarasov KV, Muller M, Sotoodehnia N, Sinner MF, Verwoert GC, Li M, Kao WH, Kottgen A, Coresh J, Bis JC, Psaty BM, Rice K, Rotter JI, Rivadeneira F, Hofman A, Kors JA, Stricker BH, Uitterlinden AG, van Duijn CM, Beckmann BM, Sauter W, Gieger C, Lubitz SA, Newton- Cheh C, Wang TJ, Magnani JW, Schnabel RB, Chung MK, Barnard J, Smith JD, Van Wagoner DR, Vasan RS, Aspelund T, Eiriksdottir G, Harris TB, Launer LJ, Najjar SS, Lakatta E, Schlessinger D, Uda M, Abecasis GR, Muller-Myhsok B, Ehret GB, Boerwinkle E, Chakravarti A, Soliman EZ, Lunetta KL, Perz S, Wichmann HE, Meitinger T, Levy D, Gudnason V, Ellinor PT, Sanna S, Kaab S, Witteman JC, Alonso A, Benjamin EJ, Heckbert SR. Genome-wide association study of PR interval. Nat Genet. 2010. 42: 153-159. https://doi.org/10.1038/ng.517
  20. Roth DM, Swaney JS, Dalton ND, Gilpin EA, Ross J Jr. Impact of anesthesia on cardiac function during echocardiography in mice. Am J Physiol Heart Circ Physiol. 2002. 282: H2134 -H2140. https://doi.org/10.1152/ajpheart.00845.2001
  21. Sandercock GR, Brodie DA. The role of heart rate variability in prognosis for different modes of death in chronic heart failure. Pacing Clin Electrophysiol. 2006. 29: 892-904. https://doi.org/10.1111/j.1540-8159.2006.00457.x
  22. Shah AP, Siedlecka U, Gandhi A, Navaratnarajah M, Al-Saud SA, Yacoub MH, Terracciano CM. Genetic background affects function and intracellular calcium regulation of mouse hearts. Cardiovasc Res. 2010. 87: 683-693. https://doi.org/10.1093/cvr/cvq111
  23. Sotoodehnia N, Isaacs A, de Bakker PI, Dorr M, Newton-Cheh C, Nolte IM, van der Harst P, Muller M, Eijgelsheim M, Alonso A, Hicks AA, Padmanabhan S, Hayward C, Smith AV, Polasek O, Giovannone S, Fu J, Magnani JW, Marciante KD, Pfeufer A, Gharib SA, Teumer A, Li M, Bis JC, Rivadeneira F, Aspelund T, Kottgen A, Johnson T, Rice K, Sie MP, Wang YA, Klopp N, Fuchsberger C, Wild SH, Mateo Leach I, Estrada K, Volker U, Wright AF, Asselbergs FW, Qu J, Chakravarti A, Sinner MF, Kors JA, Petersmann A, Harris TB, Soliman EZ, Munroe PB, Psaty BM, Oostra BA, Cupples LA, Perz S, de Boer RA, Uitterlinden AG, Volzke H, Spector TD, Liu FY, Boerwinkle E, Dominiczak AF, Rotter JI, van Herpen G, Levy D, Wichmann HE, van Gilst WH, Witteman JC, Kroemer HK, Kao WH, Heckbert SR, Meitinger T, Hofman A, Campbell H, Folsom AR, van Veldhuisen DJ, Schwienbacher C, O'Donnell CJ, Volpato CB, Caulfield MJ, Connell JM, Launer L, Lu X, Franke L, Fehrmann RS, te Meerman G, Groen HJ, Weersma RK, van den Berg LH, Wijmenga C, Ophoff RA, Navis G, Rudan I, Snieder H, Wilson JF, Pramstaller PP, Siscovick DS, Wang TJ, Gudnason V, van Duijn CM, Felix SB, Fishman GI, Jamshidi Y, Stricker BH, Samani NJ, Kaab S, Arking DE. Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction. Nat Genet. 2010. 42: 1068 -1076. https://doi.org/10.1038/ng.716
  24. Stypmann J. Doppler ultrasound in mice. Echocardiography. 2007. 24: 97-112.
  25. Uechi M, Asai K, Osaka M, Smith A, Sato N, Wagner TE, Ishikawa Y, Hayakawa H, Vatner DE, Shannon RP, Homcy CJ, Vatner SF. Depressed heart rate variability and arterial baroreflex in conscious transgenic mice with overexpression of cardiac Gsa. Circ Res. 1998. 82: 416-423. https://doi.org/10.1161/01.RES.82.4.416
  26. Xu Q, Ming Z, Dart AM, Du XJ. Optimizing dosage of ketamine and xylazine in murine echocardiography. Clin Exp Pharmacol Physiol. 2007. 34: 499-507. https://doi.org/10.1111/j.1440-1681.2007.04601.x
  27. Yang XP, Liu YH, Rhaleb NE, Kurihara N, Kim HE, Carretero OA. Echocardiographic assessment of cardiac function in conscious and anesthetized mice. Am J Physiol. 1999. 277: H1967-H1974.
  28. Zhao X, Ho D, Gao S, Hong C, Vatner DE, Vatner SF. Arterial pressure monitoring in mice. Curr Protoc Mouse Biol. 2011. 1: 105-122.