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Comprehensive echocardiographic assessment of biventricular function in the rabbit, animal model in cardiovascular research: feasibility and normal values

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Abstract

Quantification of cardiac structure and function is central in cardiovascular research. Rabbits are valuable research models of cardiovascular human disease; however, there is little normal data available. The aim of this study was to investigate feasibility and provide normal values for comprehensive echocardiographic assessment of biventricular function in rabbits. New Zealand white rabbits underwent trans-thoracic echocardiography using a general electric (GE) Vivid 7/E9 system with a 10 MHz transducer, under light sedation, to evaluate biventricular function and dimensions. Images for two-dimensional, M-mode, tissue Doppler imaging (TDI) and speckle-tracking strain echocardiography were acquired and analysed. 55 male rabbits (sized matched with a newborn human baby) were studied, mean weight was 2.9 ± 0.23 kg. Adequate images were obtained in 90% for the left ventricle (LV) and 80% for the right ventricle (RV). Two-dimensional speckle-tracking strain was feasible in 60%. Average heart rate was 248 ± 36 beats per minute; LV ejection faction 72 ± 8.0; RV fractional area change 45.9 ± 9.0%; RV myocardial performance index 0.39 ± 0.35; tricuspid annular planar systolic excursion 0.60 ± 0.24 cm. LV TDI parameters were S’ 8.6 ± 3.1 cm/s; E’ 12.0 ± 4.46 cm/s. RV TDI parameters were S’ 10.49 ± 3.18; E’ 14.95 ± 4.64 cm/s. LV and RV global peak systolic longitudinal strain were −17 ± 5 and −22 ± 8%, respectively. Comprehensive investigation of biventricular dimensions and function by echocardiography is feasible in the rabbit. Apical views and strain imaging have lower feasibility. Normal values of LV and RV functional parameters are with comparable values to human children. Animal cardiovascular research is key to develop new goals in clinical practice.

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Abbreviations

RV:

Right ventricle

LV:

Left ventricle

NZW:

New Zealand White

CV:

Cardiovascular

BSA:

Body surface area

TDI:

Tissue Doppler

TAPSE:

Tricuspid annular plane systolic excursion

FAC:

Fractional area change

MPI:

Myocardial performance index

EF:

Ejection fraction

ICC:

Intra-class correlation

AVM:

Average variation of the mean

References

  1. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ (2015) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18(12):1440–1463. doi:10.1016/j.echo.2005.10.005

    Article  Google Scholar 

  2. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 16(3):233–270. doi:10.1093/ehjci/jev014

    Article  PubMed  Google Scholar 

  3. Wang YT, Popovic ZB, Efimov IR, Cheng Y (2012) Longitudinal study of cardiac remodelling in rabbits following infarction. Can J Cardiol 28(2):230–238. doi:10.1016/j.cjca.2011.11.003

    Article  PubMed  PubMed Central  Google Scholar 

  4. Smiseth OA, Torp H, Opdahl A, Haugaa KH, Urheim S (2015) Myocardial strain imaging: how useful is it in clinical decision making? Eur Heart J 37(15):1196–1207. doi:10.1093/eurheartj/ehv529

    Article  PubMed  PubMed Central  Google Scholar 

  5. Stanton T, Leano R, Marwick TH (2009) Prediction of all-cause mortality from global longitudinal speckle strain: comparison with ejection fraction and wall motion scoring. Circ Cardiovasc Imaging 2(5):356–364. doi:10.1161/CIRCIMAGING.109.862334

    Article  PubMed  Google Scholar 

  6. Yingchoncharoen T, Agarwal S, Popovic ZB, Marwick TH (2012) Normal ranges of left ventricular strain: a meta-analysis. J Am Soc Echocardiogr 26(2):185–191. doi:10.1016/j.echo.2012.10.008

    Article  PubMed  Google Scholar 

  7. Mignot A, Donal E, Zaroui A, Reant P, Salem A, Hamon C, Monzy S, Roudaut R, Habib G, Lafitte S (2010) Global longitudinal strain as a major predictor of cardiac events in patients with depressed left ventricular function: a multicenter study. J Am Soc Echocardiogr 23(10):1019–1024. doi:10.1016/j.echo.2010.07.019

    Article  PubMed  Google Scholar 

  8. Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, Lai WW, Geva T (2010) Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr 23(5):465–495. doi:10.1016/j.echo.2010.03.019

    Article  PubMed  Google Scholar 

  9. Forfia PR, Fisher MR, Mathai SC, Housten-Harris T, Hemnes AR, Borlaug BA, Chamera E, Corretti MC, Champion HC, Abraham TP, Girgis RE, Hassoun PM (2006) Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med 174(9):1034–1041. doi:10.1164/rccm.200604-547OC

    Article  PubMed  Google Scholar 

  10. Giardini A, Specchia S, Tacy TA, Coutsoumbas G, Gargiulo G, Donti A, Formigari R, Bonvicini M, Picchio FM (2007) Usefulness of cardiopulmonary exercise to predict long-term prognosis in adults with repaired tetralogy of Fallot. Am J Cardiol 99(10):1462–1467. doi:10.1016/j.amjcard.2006.12.076

    Article  PubMed  Google Scholar 

  11. Santos A, Fernandez-Friera L, Villalba M, Lopez-Melgar B, Espana S, Mateo J, Mota RA, Jimenez-Borreguero J, Ruiz-Cabello J (2015) Cardiovascular imaging: what have we learned from animal models? Front Pharmacol 6:227. doi:10.3389/fphar.2015.00227

    PubMed  PubMed Central  Google Scholar 

  12. Zehnder AM, Hawkins MG, Trestrail EA, Holt RW, Kent MS (2012) Calculation of body surface area via computed tomography-guided modeling in domestic rabbits (Oryctolagus cuniculus). Am J Vet Res 73(12):1859–1863. doi:10.2460/ajvr.73.12.1859

    Article  PubMed  PubMed Central  Google Scholar 

  13. Brion L, Fleischman AR, Schwartz GJ (1985) Evaluation of four length-weight formulas for estimating body surface area in newborn infants. J Pediatr 107(5):801–803

    Article  CAS  PubMed  Google Scholar 

  14. Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr 93(1):62–66

    Article  CAS  PubMed  Google Scholar 

  15. Stypmann J, Engelen MA, Breithardt AK, Milberg P, Rothenburger M, Breithardt OA, Breithardt G, Eckardt L, Cordula PN (2007) Doppler echocardiography and tissue Doppler imaging in the healthy rabbit: differences of cardiac function during awake and anaesthetised examination. Int J Cardiol 115(2):164–170. doi:10.1016/j.ijcard.2006.03.006

    Article  PubMed  Google Scholar 

  16. Zhou J, Pu DR, Tian LQ, Tong H, Liu HY, Tang Y, Zhou QC (2015) Noninvasive assessment of myocardial mechanics of the left ventricle in rabbits using velocity vector imaging. Med Sci Monit Basic Res 21:109–115. doi:10.12659/MSMBR.894053

    Article  PubMed  PubMed Central  Google Scholar 

  17. WH Du XW, XQ Xiong, T li, HP Liang (2016) Role of speckle tracking imaging in the assesment of myocardial regional ventricular function in experimental blunt cardiac injury Chinese. J Traumatol 18(4):223–228

    Article  Google Scholar 

  18. Hofstetter R, Mayr A, von Bernuth G (1982) Computer analysis of cardiac contractility variables obtained by M-mode echocardiography in normal newborns. Br Heart J 48(6):525–528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Guzeltas A, Eroglu AG (2011) Reference values for echocardiographic measurements of healthy newborns. Cardiol Young 22(2):152–157. doi:10.1017/S1047951111001259

    Article  PubMed  Google Scholar 

  20. Hagan AD, Deely WJ, Sahn D, Friedman WF (1973) Echocardiographic criteria for normal newborn infants. Circulation 48(6):1221–1226

    Article  CAS  PubMed  Google Scholar 

  21. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB (2010) 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 23(7):685–713. doi:10.1016/j.echo.2010.05.010

    Article  PubMed  Google Scholar 

  22. Kjaergaard J, Akkan D, Iversen KK, Kober L, Torp-Pedersen C, Hassager C (2007) Right ventricular dysfunction as an independent predictor of short- and long-term mortality in patients with heart failure. Eur J Heart Fail 9(6–7):610–616. doi:10.1016/j.ejheart.2007.03.001

    Article  PubMed  Google Scholar 

  23. Koestenberger M, Ravekes W (2011) Right ventricular function parameters in the neonatal population. J Am Soc Echocardiogr 25(2):243–244. doi:10.1016/j.echo.2011.12.004

    Article  PubMed  Google Scholar 

  24. Arce OX, Knudson OA, Ellison MC, Baselga P, Ivy DD, Degroff C, Valdes-Cruz L (2002) Longitudinal motion of the atrioventricular annuli in children: reference values, growth related changes, and effects of right ventricular volume and pressure overload. J Am Soc Echocardiogr 15(9):906–916 pii]

    Article  PubMed  Google Scholar 

  25. Mor Avi V LR, Badano L, Belohlavek M, Cardim N, Derumeaux G, Galderisi M, Marwick T, Nagueh S, Sengupta P, Sicari R, Smiseth O, Vannan M, Voigt J, Zamorano JL (2011) Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications. J Am Soc Echocardiogr 24:277–313

    Article  PubMed  Google Scholar 

  26. Oana M DJ, Voigt J (2016) Recent advances in echocardiography: strain and strain rate imaging. F1000 Rev 787. doi:10.12688/f1000research.7228.1

    Google Scholar 

  27. Dallaire F, Slorach C, Hui W, Sarkola T, Friedberg MK, Bradley TJ, Jaeggi E, Dragulescu A, Har RL, Cherney DZ, Mertens L (2015) Reference values for pulse wave Doppler and tissue Doppler imaging in pediatric echocardiography. Circ Cardiovasc Imaging 8(2):e002167. doi:10.1161/CIRCIMAGING.114.002167

    Article  PubMed  Google Scholar 

  28. Healy LJ, Jiang Y, Hsu EW (2011) Quantitative comparison of myocardial fiber structure between mice, rabbit, and sheep using diffusion tensor cardiovascular magnetic resonance. J Cardiovasc Magn Reson 13:74. doi:10.1186/1532-429X-13-74

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sato Y, Maruyama A, Ichihashi K (2012) Myocardial strain of the left ventricle in normal children. J Cardiol 60(2):145–149. doi:10.1016/j.jjcc.2012.01.015

    Article  PubMed  Google Scholar 

  30. Levy PT, Machefsky A, Sanchez AA, Patel MD, Rogal S, Fowler S, Yaeger L, Hardi A, Holland MR, Hamvas A, Singh GK (2016) Reference ranges of left ventricular strain measures by two-dimensional speckle-tracking echocardiography in children: a systematic review and meta-analysis. J Am Soc Echocardiogr 29(3):209–225. doi:10.1016/j.echo.2015.11.016

    Article  PubMed  Google Scholar 

  31. Jashari H, Rydberg A, Ibrahimi P, Bajraktari G, Kryeziu L, Jashari F, Henein MY (2015) Normal ranges of left ventricular strain in children: a meta-analysis. Cardiovasc Ultrasound 13:37. doi:10.1186/s12947-015-0029-010

    Article  PubMed  PubMed Central  Google Scholar 

  32. Berg R, Meister R, Eigendorf B, Litschko A, Loos R, Wensch HJ (1976) Anatomical studies on the quantitative development of liver, heart and adrenal glands in white New Zealand rabbits. Arch Exp Veterinarmed 30(2):217–225

    CAS  PubMed  Google Scholar 

  33. Laboratories CR (2013) New Zealand white rabbits. Model information sheet. Charles River Laboratories International Inc, Wilmington

    Google Scholar 

  34. Masoud I, Shapiro F, Kent R, Moses A (1986) A longitudinal study of the growth of the New Zealand white rabbit: cumulative and biweekly incremental growth rates for body length, body weight, femoral length, and tibial length. J Orthop Res 4(2):221–231. doi:10.1002/jor.1100040211

    Article  CAS  PubMed  Google Scholar 

  35. Weidemann F, Jamal F, Kowalski M, Kukulski T, D’Hooge J, Bijnens B, Hatle L, De Scheerder I, Sutherland GR (2002) Can strain rate and strain quantify changes in regional systolic function during dobutamine infusion, B-blockade, and atrial pacing–implications for quantitative stress echocardiography. J Am Soc Echocardiogr 15(5):416–424

    Article  PubMed  Google Scholar 

  36. Negoita M, Zolgharni M, Dadkho E, Pernigo M, Mielewczik M, Cole GD, Dhutia NM, Francis DP (2016) Frame rate required for speckle tracking echocardiography: a quantitative clinical study with open-source, vendor-independent software. Int J Cardiol 218:31–36. doi:10.1016/j.ijcard.2016.05.047

    Article  PubMed  Google Scholar 

  37. Duelsner A, Bondke Persson A (2013) Animal models in cardiovascular research. Acta Physiol 208(1):1–5. doi:10.1111/apha.12074

    Article  CAS  Google Scholar 

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Acknowledgements

This research was partially funded by a grant award from the Labatt Family Heart Centre, Toronto, Canada.

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Correspondence to Sara Roldan Ramos or Mark K. Friedberg.

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Animal research

This study was approved prior to experiments by the Animal Ethics Committee at the Sickkids Research Institute and performed according to the Canadian Council for Animal Care guidelines. The authors confirm that these guidelines have been followed.

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We confirm that this manuscript is an original work and has not been published elsewhere and is not under consideration by any other journal. All authors have approved the manuscript and agree with its submission.

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Ramos, S.R., Pieles, G., Hui, W. et al. Comprehensive echocardiographic assessment of biventricular function in the rabbit, animal model in cardiovascular research: feasibility and normal values. Int J Cardiovasc Imaging 34, 367–375 (2018). https://doi.org/10.1007/s10554-017-1238-4

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