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Non-invasive in vivo measurement of cardiac output in C57BL/6 mice using high frequency transthoracic ultrasound: evaluation of gender and body weight effects

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Abstract

Even though mice are being increasingly used as models for human cardiovascular diseases, non-invasive monitoring of cardiovascular parameters such as cardiac output (CO) in this species is challenging. In most cases, the effects of gender and body weight (BW) on these parameters have not been studied. The objective of this study was to provide normal reference values for CO in C57BL/6 mice, and to describe possible gender and/or BW associated differences between them. We used 30-MHz transthoracic Doppler ultrasound to measure hemodynamic parameters in the ascending aorta [heart rate (HR), stroke volume (SV), stroke index (SI), CO, and cardiac index (CI)] in ten anesthetized mice of either sex. No differences were found for HR, SV, and CO. Both SI and CI were statistically lower in males. However, after normalization for BW, these differences disappeared. These results suggest that if comparisons of cardiovascular parameters are to be made between male and female mice, values should be standardized for BW.

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References

  1. Paigen K (1995) A miracle enough: the power of mice. Nat Med 1:215–220

    Article  PubMed  CAS  Google Scholar 

  2. Doevendans PA, Daemen MJ, de Muinck ED, Smits JF (1998) Cardiovascular phenotyping in mice. Cardiovasc Res 39:34–49

    Article  PubMed  CAS  Google Scholar 

  3. Fitzgerald SM, Gan L, Wickman A, Bergstrom G (2003) Cardiovascular and renal phenotyping of genetically modified mice: a challenge for traditional physiology. Clin Exp Pharmacol Physiol 30:207–216

    Article  PubMed  CAS  Google Scholar 

  4. Tanaka N, Dalton N, Mao L, Rockman HA, Peterson KL, Gottshall KR et al (1996) Transthoracic echocardiography in models of cardiac disease in the mouse. Circulation 94:1109–1117

    Article  PubMed  CAS  Google Scholar 

  5. Yang XP, Liu YH, Rhaleb NE, Kurihara N, Kim HE, Carretero OA (1999) Echocardiographic assessment of cardiac function in conscious and anesthetized mice. Am J Physiol 277:H1967–H1974

    PubMed  CAS  Google Scholar 

  6. Collins KA, Korcarz CE, Lang RM (2003) Use of echocardiography for the phenotypic assessment of genetically altered mice. Physiol Genomics 13:227–239

    PubMed  Google Scholar 

  7. Zhou YQ, Foster FS, Qu DW, Zhang M, Harasiewicz KA, Adamson SL (2002) Applications for multifrequency ultrasound biomicroscopy in mice from implantation to adulthood. Physiol Genomics 10:113–126

    PubMed  CAS  Google Scholar 

  8. Zhou YQ, Foster FS, Nieman BJ, Davidson L, Chen XJ, Henkelman RM (2004) Comprehensive transthoracic cardiac imaging in mice using ultrasound biomicroscopy with anatomical confirmation by magnetic resonance imaging. Physiol Genomics 18:232–244

    Article  PubMed  Google Scholar 

  9. McVeigh ER (2006) Emerging imaging techniques. Circ Res 98:879–886

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Hartley CJ, Taffet GE, Reddy AK, Entman ML, Michael LH (2002) Noninvasive cardiovascular phenotyping in mice. ILAR J 43:147–158

    Article  PubMed  CAS  Google Scholar 

  11. Janssen B, Debets J, Leenders P, Smits J (2002) Chronic measurement of cardiac output in conscious mice. Am J Physiol 282:R928–R935

    CAS  Google Scholar 

  12. Carlsson M, Andersson R, Bloch KM, Steding-Ehrenborg K, Mosen H, Stahlberg F et al (2012) Cardiac output and cardiac index measured with cardiovascular magnetic resonance in healthy subjects, elite athletes and patients with congestive heart failure. J Cardiovasc Magn Reson 28(14):51

    Article  Google Scholar 

  13. Schneider JE, Wiesmann F, Lygate CA, Neubauer S (2006) How to perform an accurate assessment of cardiac function in mice using high-resolution magnetic resonance imaging. J Cardiovasc Magn Reson 8:693–701

    Article  PubMed  Google Scholar 

  14. Huntsman LL, Stewart DK, Barnes SR, Franklin SB, Colocousis JS, Hessel EA (1983) Noninvasive Doppler determination of cardiac output in man. Clinical validation. Circulation 67:593–602

    Article  PubMed  CAS  Google Scholar 

  15. Tournoux F, Petersen B, Thibault H, Zou L, Raher MJ, Kurtz B et al (2011) Validation of noninvasive measurements of cardiac output in mice using echocardiography. J Am Soc Echocardiogr 24:465–470

    Article  PubMed  PubMed Central  Google Scholar 

  16. Khankin EV, Hacker MR, Zelop CM, Karumanchi SA, Rana S (2012) Intravital high-frequency ultrasonography to evaluate cardiovascular and uteroplacental blood flow in mouse pregnancy. Pregnancy Hypertens 2:84–92

    PubMed  PubMed Central  Google Scholar 

  17. Tomita H, Hagaman J, Friedman MH, Maeda N (2012) Relationship between hemodynamics and atherosclerosis in aortic arches of apolipoprotein E-null mice on 129S6/SvEvTac and C57BL/6 J genetic backgrounds. Atherosclerosis 220:78–85

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Stypmann J, Engelen MA, Epping C, van Rijen HV, Milberg P, Bruch C et al (2006) Age and gender related reference values for transthoracic Doppler-echocardiography in the anesthetized CD1 mouse. Int J Cardiovasc Imaging 22:353–362

    Article  PubMed  Google Scholar 

  19. National Research Council (US) of the National Academies (2011) Guide for care and use of laboratory animals. The National Academies Press, Washington, pp 155–195

  20. Cahill L (2006) Why sex matters for neuroscience. Nat Rev Neurosci 7:477–484

    Article  PubMed  CAS  Google Scholar 

  21. Holdcroft A (2007) Integrating the dimensions of sex and gender into basic life sciences research: methodologic and ethical issues. Gend Med 4(Suppl B):S64–S74

    Article  PubMed  Google Scholar 

  22. Riesen S, Schmid V, Gaschen L, Busato A, Lang J (2002) Doppler measurement of splanchnic blood flow during digestion in unsedated normal dogs. Vet Radiol Ultrasound 43:554–560

    Article  PubMed  Google Scholar 

  23. Szatmari V, Sotonyi P, Voros K (2001) Normal duplex Doppler waveforms of major abdominal blood vessels in dogs: a review. Vet Radiol Ultrasound 42:93–107

    Article  PubMed  CAS  Google Scholar 

  24. Ni M, Zhang M, Ding SF, Chen WQ, Zhang Y (2008) Micro-ultrasound imaging assessment of carotid plaque characteristics in apolipoprotein-E knockout mice. Atherosclerosis 197:64–71

    Article  PubMed  CAS  Google Scholar 

  25. Fox JG, Stephen WB, Davisson MT, Newcomer CE, Quimby FW, Smith AL (2007) The mouse in biomedical research. Elsevier, US

    Google Scholar 

  26. Wu J, Bu L, Gong H, Jiang G, Li L, Ma H et al (2010) Effects of heart rate and anesthetic timing on high-resolution echocardiographic assessment under isoflurane anesthesia in mice. J Ultrasound Med 29:1771–1778

    PubMed  Google Scholar 

  27. Foster FS, Zhang MY, Zhou YQ, Liu G, Mehi J, Cherin E et al (2002) A new ultrasound instrument for in vivo microimaging of mice. Ultrasound Med Biol 28:1165–1172

    Article  PubMed  CAS  Google Scholar 

  28. Feintuch A, Ruengsakulrach P, Lin A, Zhang J, Zhou YQ, Bishop J et al (2007) Hemodynamics in the mouse aortic arch as assessed by MRI, ultrasound, and numerical modeling. Am J Physiol Circ Physiol 292:H884–H892

    Article  CAS  Google Scholar 

  29. Stoyanova E, Trudel M, Felfly H, Garcia D, Cloutier G (2007) Characterization of circulatory disorders in beta-thalassemic mice by noninvasive ultrasound biomicroscopy. Physiol Genomics 29:84–90

    Article  PubMed  CAS  Google Scholar 

  30. Baumann PQ, Sobel BE, Tarikuz Zaman AK, Schneider DJ (2008) Gender-dependent differences in echocardiographic characteristics of murine hearts. Echocardiography 25:739–748

    Article  PubMed  Google Scholar 

  31. Janssen BJ, De Celle T, Debets JJ, Brouns AE, Callahan MF, Smith TL (2004) Effects of anesthetics on systemic hemodynamics in mice. Am J Physiol Circ Physiol 287:H1618–H1624

    Article  CAS  Google Scholar 

  32. Meyer RE, Fish RE (2005) A review of tribromoethanol anesthesia for production of genetically engineered mice and rats. Lab Anim 34:47–52

    Article  Google Scholar 

  33. Roth DM, Swaney JS, Dalton ND, Gilpin EA, Ross J Jr (2002) Impact of anesthesia on cardiac function during echocardiography in mice. Am J Physiol Circ Physiol 282:H2134–H2140

    CAS  Google Scholar 

  34. Klabunde RE (2005) Cardiovascular physiology concepts. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  35. Pearce WH, Slaughter MS, LeMaire S, Salyapongse AN, Feinglass J, McCarthy WJ et al (1993) Aortic diameter as a function of age, gender, and body surface area. Surgery 114:691–697

    PubMed  CAS  Google Scholar 

  36. Salton CJ, Chuang ML, O’Donnell CJ, Kupka MJ, Larson MG, Kissinger KV et al (2002) Gender differences and normal left ventricular anatomy in an adult population free of hypertension. A cardiovascular magnetic resonance study of the Framingham Heart Study Offspring cohort. J Am Coll Cardiol 39:1055–1060

    Article  PubMed  Google Scholar 

  37. Mao SS, Ahmadi N, Shah B, Beckmann D, Chen A, Ngo L et al (2008) Normal thoracic aorta diameter on cardiac computed tomography in healthy asymptomatic adults: impact of age and gender. Acad Radiol 15:827–834

    Article  PubMed  PubMed Central  Google Scholar 

  38. Wolak A, Gransar H, Thomson LE, Friedman JD, Hachamovitch R, Gutstein A et al (2008) Aortic size assessment by noncontrast cardiac computed tomography: normal limits by age, gender, and body surface area. JACC Cardiovasc Imaging 1:200–209

    Article  PubMed  Google Scholar 

  39. Rottman JN, Ni G, Khoo M, Wang Z, Zhang W, Anderson ME et al (2003) Temporal changes in ventricular function assessed echocardiographically in conscious and anesthetized mice. J Am Soc Echocardiogr 16:1150–1157

    Article  PubMed  Google Scholar 

  40. Breslow JL (1996) Mouse models of atherosclerosis. Science 272:685–688

    Article  PubMed  CAS  Google Scholar 

  41. Daugherty A, Cassis LA (2004) Mouse models of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 24:429–434

    Article  PubMed  CAS  Google Scholar 

  42. Westrick RJ, Winn ME, Eitzman DT (2007) Murine models of vascular thrombosis. Arterioscler Thromb Vasc Biol 27:2079–2093

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant (Beca de Formación de Profesorado Universitario-FPU) of the Ministerio de Educación, Cultura y Deporte del Gobierno de España.

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Authors and Affiliations

  1. Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Edifici V, Campus, 08193, Barcelona, Spain

    Elisabet Domínguez, Rosa Novellas, Maria Montserrat Rivera del Alamo & Yvonne Espada

  2. Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Barcelona, Spain

    Jesús Ruberte & Marc Navarro

  3. Mouse Imaging Plattform, Centre de Biotecnologia i Teràpia Gènica (CBATEG), Universitat Autònoma de Barcelona, Barcelona, Spain

    Jesús Ruberte & Marc Navarro

  4. Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain

    José Ríos

  5. IDIBAPS (Institut d’investigacions Biomèdiques August Pi i Sunyer), Hospital Clínic Barcelona, Barcelona, Spain

    José Ríos

Authors
  1. Elisabet Domínguez
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  2. Jesús Ruberte
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  4. Rosa Novellas
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  5. Maria Montserrat Rivera del Alamo
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  6. Marc Navarro
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  7. Yvonne Espada
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Correspondence to Elisabet Domínguez.

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Domínguez, E., Ruberte, J., Ríos, J. et al. Non-invasive in vivo measurement of cardiac output in C57BL/6 mice using high frequency transthoracic ultrasound: evaluation of gender and body weight effects. Int J Cardiovasc Imaging 30, 1237–1244 (2014). https://doi.org/10.1007/s10554-014-0454-4

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  • DOI: https://doi.org/10.1007/s10554-014-0454-4

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