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Comprehensive Echocardiographic Assessment of the Right Ventricle in Murine Models

  • Kohut, Andrew (Division of Cardiology, Drexel University College of Medicine) ;
  • Patel, Nishi (Department of Medicine, Drexel University College of Medicine) ;
  • Singh, Harpreet (Division of Cardiology, Drexel University College of Medicine)
  • Received : 2016.05.26
  • Accepted : 2016.08.03
  • Published : 2016.09.27

Abstract

Background: Non-invasive high-resolution echocardiography to evaluate cardiovascular function of small animals is increasingly being used due to availability of genetically engineered murine models. Even though guidelines and standard values for humans were revised by the American Society of Echocardiography, evaluations on murine models are not performed according to any standard protocols. These limitations are preventing translation of preclinical evaluations to clinical meaningful conclusions. We have assessed the right heart of two commonly used murine models according to standard clinical guidelines, and provided the practical guide and sample values for cardiac assessments. Methods: Right heart echocardiography evaluations of CD1 and C57BL/6 mice were performed under 1-3% isoflurane anesthesia using $Vevo^{(R)}$ 2100 Imaging System with a high-frequency (18-38 MHz) probe (VisualSonics MS400). We have provided a practical guide on how to image and assess the right heart of a mouse which is frequently used to evaluate development of right heart failure due to pulmonary hypertension. results: Our results show significant differences between CD1 and C57BL/6 mice. Right ventricle structural assessment showed significantly larger (p < 0.05) size, and pulmonary artery diameter in CD1 mice (n = 11) compared to C57BL/6 mice (n = 15). Right heart systolic and diastolic functions were similar for both strains. Conclusion: Our practical guide on how to image and assess the right heart of murine models provides the first comprehensive values which can be used for preclinical research studies using echocardiography. Additionally, our results indicate that there is a high variability between mouse species and experimental models should be carefully selected for cardiac evaluations.

Keywords

Acknowledgement

Supported by : CTRI, CURE, AHA SDG, NIH/NHLBI

References

  1. Umar S, Lee JH, de Lange E, Iorga A, Partow-Navid R, Bapat A, van der Laarse A, Saggar R, Saggar R, Ypey DL, Karagueuzian HS, Eghbali M. Spontaneous ventricular fibrillation in right ventricular failure secondary to chronic pulmonary hypertension. Circ Arrhythm Electrophysiol 2012;5:181-90. https://doi.org/10.1161/CIRCEP.111.967265
  2. Sharma S, Umar S, Potus F, Iorga A, Wong G, Meriwether D, Breuils-Bonnet S, Mai D, Navab K, Ross D, Navab M, Provencher S, Fogelman AM, Bonnet S, Reddy ST, Eghbali M. Apolipoprotein A-I mimetic peptide 4F rescues pulmonary hypertension by inducing microRNA-193-3p. Circulation 2014;130:776-85. https://doi.org/10.1161/CIRCULATIONAHA.114.007405
  3. Iorga A, Li J, Sharma S, Umar S, Bopassa JC, Nadadur RD, Centala A, Ren S, Saito T, Toro L, Wang Y, Stefani E, Eghbali M. Rescue of pressure overload-induced heart failure by estrogen therapy. J Am Heart Assoc 2016 Jan 22 [Epub]. http://dx.doi.org/10.1161/JAHA.115.002482.
  4. Cheng HW, Fisch S, Cheng S, Bauer M, Ngoy S, Qiu Y, Guan J, Mishra S, Mbah C, Liao R. Assessment of right ventricular structure and function in mouse model of pulmonary artery constriction by transthoracic echocardiography. J Vis Exp 2014;(84):e51041.
  5. Scherrer-Crosbie M, Kurtz B. Ventricular remodeling and function: insights using murine echocardiography. J Mol Cell Cardiol 2010;48:512-7. https://doi.org/10.1016/j.yjmcc.2009.07.004
  6. Gomez-Arroyo J, Saleem SJ, Mizuno S, Syed AA, Bogaard HJ, Abbate A, Taraseviciene-Stewart L, Sung Y, Kraskauskas D, Farkas D, Conrad DH, Nicolls MR, Voelkel NF. A brief overview of mouse models of pulmonary arterial hypertension: problems and prospects. Am J Physiol Lung Cell Mol Physiol 2012;302:L977-91. https://doi.org/10.1152/ajplung.00362.2011
  7. Stypmann J. Doppler ultrasound in mice. Echocardiography 2007;24:97-112.
  8. Copley SJ, Mathew TP. Advances in echocardiography. Imaging 2006; 18:160-5. https://doi.org/10.1259/imaging/55305042
  9. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685-713. https://doi.org/10.1016/j.echo.2010.05.010
  10. Singh H, Lu R, Bopassa JC, Meredith AL, Stefani E, Toro L. MitoBK (Ca) is encoded by the Kcnma1 gene, and a splicing sequence defines its mitochondrial location. Proc Natl Acad Sci U S A 2013;110:10836-41. https://doi.org/10.1073/pnas.1302028110
  11. Ponnalagu D, Gururaja Rao S, Farber J, Xin W, Hussain AT, Shah K, Tanda S, Berryman M, Edwards JC, Singh H. Molecular identity of cardiac mitochondrial chloride intracellular channel proteins. Mitochondrion 2016;27:6-14. https://doi.org/10.1016/j.mito.2016.01.001
  12. Janssen BJ, De Celle T, Debets JJ, Brouns AE, Callahan MF, Smith TL. Effects of anesthetics on systemic hemodynamics in mice. Am J Physiol Heart Circ Physiol 2004;287:H1618-24. https://doi.org/10.1152/ajpheart.01192.2003
  13. Gao S, Ho D, Vatner DE, Vatner SF. Echocardiography in mice. Curr Protoc Mouse Biol 2011;1:71-83.
  14. 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:H2134-40. https://doi.org/10.1152/ajpheart.00845.2001
  15. Wikstrom J, Gronros J, Gan LM. Adenosine induces dilation of epicardial coronary arteries in mice: relationship between coronary flow velocity reserve and coronary flow reserve in vivo using transthoracic echocardiography. Ultrasound Med Biol 2008;34:1053-62. https://doi.org/10.1016/j.ultrasmedbio.2007.12.004
  16. Broberg CS, Pantely GA, Barber BJ, Mack GK, Lee K, Thigpen T, Davis LE, Sahn D, Hohimer AR. Validation of the myocardial performance index by echocardiography in mice: a noninvasive measure of left ventricular function. J Am Soc Echocardiogr 2003;16:814-23. https://doi.org/10.1067/S0894-7317(03)00399-7
  17. Zhou YQ, Foster FS, Parkes R, Adamson SL. Developmental changes in left and right ventricular diastolic filling patterns in mice. Am J Physiol Heart Circ Physiol 2003;285:H1563-75. https://doi.org/10.1152/ajpheart.00384.2003
  18. Egemnazarov B, Schmidt A, Crnkovic S, Sydykov A, Nagy BM, Kovacs G, Weissmann N, Olschewski H, Olschewski A, Kwapiszewska G, Marsh LM. Pressure overload creates right ventricular diastolic dysfunction in a mouse model: assessment by echocardiography. J Am Soc Echocardiogr 2015;28:828-43. https://doi.org/10.1016/j.echo.2015.02.014
  19. Vinhas M, Araujo AC, Ribeiro S, Rosario LB, Belo JA. Transthoracic echocardiography reference values in juvenile and adult 129/Sv mice. Cardiovasc Ultrasound 2013;11:12. https://doi.org/10.1186/1476-7120-11-12
  20. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelista A. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 2009;22:107-33. https://doi.org/10.1016/j.echo.2008.11.023
  21. Thibault HB, Kurtz B, Raher MJ, Shaik RS, Waxman A, Derumeaux G, Halpern EF, Bloch KD, Scherrer-Crosbie M. Noninvasive assessment of murine pulmonary arterial pressure: validation and application to models of pulmonary hypertension. Circ Cardiovasc Imaging 2010;3:157-63. https://doi.org/10.1161/CIRCIMAGING.109.887109
  22. Barnabei MS, Palpant NJ, Metzger JM. Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains. Physiol Genomics 2010;42A:103-13. https://doi.org/10.1152/physiolgenomics.00071.2010

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