Skip to main content

Advertisement

SpringerLink
Log in

Myocardial perfusion MRI shows impaired perfusion of the mouse hypertrophic left ventricle

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

There is growing consensus that myocardial perfusion deficits play a pivotal role in the transition from compensated to overt decompensated hypertrophy. The purpose of this study was to systematically study myocardial perfusion deficits in the highly relevant model of pressure overload induced hypertrophy and heart failure by transverse aortic constriction (TAC), which was not done thus far. Regional left ventricular (LV) myocardial perfusion (mL/min/g) was assessed in healthy mice (n = 6) and mice with TAC (n = 14). A dual-bolus first-pass perfusion MRI technique was employed to longitudinally quantify myocardial perfusion values between 1 and 10 weeks after surgery. LV function and morphology were quantified from cinematographic MRI. Myocardial rest perfusion values in both groups did not change significantly over time, in line with the essentially constant global LV function and mass. Myocardial perfusion was significantly decreased in TAC mice (4.2 ± 0.9 mL/min/g) in comparison to controls (7.6 ± 1.8 mL/min/g) (P = 0.001). No regional differences in perfusion were observed within the LV wall. Importantly, increased LV volumes and mass, and decreased ejection fraction correlated with decreased myocardial perfusion (P < 0.001, in all cases). Total LV blood flow was decreased in TAC mice (0.5 ± 0.1 mL/min, P < 0.001) in comparison to control mice (0.7 ± 0.2 mL/min). Myocardial perfusion in TAC mice was significantly reduced as compared to healthy controls. Perfusion was proportional to LV volume and mass, and related to decreased LV ejection fraction. Furthermore, this study demonstrates the potential of quantitative first-pass contrast-enhanced MRI for the study of perfusion deficits in the diseased mouse heart.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Denolin H, Kuhn H, Krayenbuehl HP et al (1983) The definition of heart failure. Eur Heart J 4(7):445–448

    CAS  PubMed  Google Scholar 

  2. Juenger J, Schellberg D, Kraemer S et al (2002) Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Heart 87(3):235–241

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. de Couto G, Ouzounian M, Liu PP (2010) Early detection of myocardial dysfunction and heart failure. Nat Rev Cardiol 7(6):334–344

    Article  PubMed  Google Scholar 

  4. Lloyd-Jones D, Adams RJ, Brown TM et al (2010) Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation 121(7):e46–e215

    Article  PubMed  Google Scholar 

  5. McMurray JJ, Stewart S (2000) Epidemiology, aetiology, and prognosis of heart failure. Heart 83(5):596–602

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Cokkinos DV, Pantos C (2011) Myocardial remodeling, an overview. Heart Fail Rev 16:1–4

    Article  PubMed  Google Scholar 

  7. Frey N, Olson EN (2003) Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 65:45–79

    Article  CAS  PubMed  Google Scholar 

  8. Neubauer S (2007) The failing heart—an engine out of fuel. N Engl J Med 356(11):1140–1151

    Article  PubMed  Google Scholar 

  9. Shiojima I, Sato K, Izumiya Y et al (2005) Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest 115(8):2108–2118

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Vatner SF, Hittinger L (1993) Coronary vascular mechanisms involved in decompensation from hypertrophy to heart failure. J Am Coll Cardiol 22(4 Suppl A):34A–40A

    Article  CAS  PubMed  Google Scholar 

  11. Mathiassen ON, Buus NH, Sihm I et al (2007) Small artery structure is an independent predictor of cardiovascular events in essential hypertension. J Hypertens 25(5):1021–1026

    Article  CAS  PubMed  Google Scholar 

  12. Levy BI, Schiffrin EL, Mourad JJ et al (2008) Impaired tissue perfusion: a pathology common to hypertension, obesity, and diabetes mellitus. Circulation 118(9):968–976

    Article  PubMed  Google Scholar 

  13. Dai Z, Aoki T, Fukumoto Y et al (2012) Coronary perivascular fibrosis is associated with impairment of coronary blood flow in patients with non-ischemic heart failure. J Cardiol 60(5):416–421

    Article  PubMed  Google Scholar 

  14. Hoenig MR, Bianchi C, Rosenzweig A et al (2008) The cardiac microvasculature in hypertension, cardiac hypertrophy and diastolic heart failure. Curr Vasc Pharmacol 6(4):292–300

    Article  CAS  PubMed  Google Scholar 

  15. Cecchi F, Olivotto I, Gistri R et al (2003) Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy. N Engl J Med 349(11):1027–1035

    Article  CAS  PubMed  Google Scholar 

  16. Nakajima H, Onishi K, Kurita T et al (2010) Hypertension impairs myocardial blood perfusion reserve in subjects without regional myocardial ischemia. Hypertens Res 33(11):1144–1149

    Article  PubMed  Google Scholar 

  17. Hartley CJ, Reddy AK, Madala S et al (2008) Doppler estimation of reduced coronary flow reserve in mice with pressure overload cardiac hypertrophy. Ultrasound Med Biol 34(6):892–901

    Article  PubMed Central  PubMed  Google Scholar 

  18. Givvimani S, Munjal C, Gargoum R et al (2011) Hydrogen sulfide mitigates transition from compensatory hypertrophy to heart failure. J Appl Physiol 110(4):1093–1100

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Oudit GY, Kassiri Z, Zhou J et al (2008) Loss of PTEN attenuates the development of pathological hypertrophy and heart failure in response to biomechanical stress. Cardiovasc Res 78(3):505–514

    Article  CAS  PubMed  Google Scholar 

  20. van Deel ED, de Boer M, Kuster DW et al (2011) Exercise training does not improve cardiac function in compensated or decompensated left ventricular hypertrophy induced by aortic stenosis. J Mol Cell Cardiol 50(6):1017–1025

    Article  PubMed  Google Scholar 

  21. Streif JUG, Nahrendorf M, Hiller K-H et al (2005) In vivo assessment of absolute perfusion and intracapillary blood volume in the murine myocardium by spin labeling magnetic resonance imaging. Magn Reson Med 53(3):584–592

    Article  PubMed  Google Scholar 

  22. Jacquier A, Kober F, Bun S et al (2011) Quantification of myocardial blood flow and flow reserve in rats using arterial spin labeling MRI: comparison with a fluorescent microsphere technique. NMR Biomed 24(9):1047–1053

    Article  PubMed  Google Scholar 

  23. Decking UKM, Pai VM, Bennett E et al (2004) High-resolution imaging reveals a limit in spatial resolution of blood flow measurements by microspheres. Am J Physiol Heart Circ Physiol 287(3):H1132–H1140

    Article  CAS  PubMed  Google Scholar 

  24. Coolen BF, Moonen RPM, Paulis LEM et al (2010) Mouse myocardial first-pass perfusion MR imaging. Magn Reson Med 64(6):1658–1663

    Article  PubMed  Google Scholar 

  25. Makowski M, Jansen C, Webb I et al (2010) First-pass contrast-enhanced myocardial perfusion MRI in mice on a 3-T clinical MR scanner. Magn Reson Med 64(6):1592–1598

    Article  PubMed Central  PubMed  Google Scholar 

  26. van Nierop BJ, Coolen BF, Dijk WJR et al (2012) Quantitative first-pass perfusion MRI of the mouse myocardium. Magn Reson Med 69(6):1735–1744

    Article  PubMed  Google Scholar 

  27. Rockman HA, Ross RS, Harris AN et al (1991) Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc Natl Acad Sci USA 88(18):8277–8281

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. van Nierop BJ, van Assen H, van Deel ED et al (2013) Phenotyping of left and right ventricular function in mouse models of compensated hypertrophy and heart failure with cardiac MRI. PLoS One 8(2):e55424

    Article  PubMed Central  PubMed  Google Scholar 

  29. Köstler H, Ritter C, Lipp M et al (2004) Prebolus quantitative MR heart perfusion imaging. Magn Reson Med 52(2):296–299

    Article  PubMed  Google Scholar 

  30. Jerosch-Herold M, Wilke N, Stillman AE (1998) Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution. Med Phys 25(1):73–84

    Article  CAS  PubMed  Google Scholar 

  31. Valentinuzzi ME, Geddes LA, Baker LE (1969) A simple mathematical derivation of the Stewart–Hamilton formula for the determination of cardiac output. Med Biol Eng 7(3):277–282

    Article  CAS  PubMed  Google Scholar 

  32. Kawecka-Jaszcz K, Czarnecka D, Olszanecka A et al (2008) Myocardial perfusion in hypertensive patients with normal coronary angiograms. J Hypertens 26(8):1686–1694

    Article  CAS  PubMed  Google Scholar 

  33. Izumiya Y, Shiojima I, Sato K et al (2006) Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload. Hypertension 47(5):887–893

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Duncker DJ, de Beer VJ, Merkus D (2008) Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction. Med Biol Eng Comput 46(5):485–497

    Article  PubMed Central  PubMed  Google Scholar 

  35. Bache RJ (1988) Effects of hypertrophy on the coronary circulation. Prog Cardiovasc Dis 30(6):403–440

    Article  CAS  PubMed  Google Scholar 

  36. Kober F, Iltis I, Cozzone PJ et al (2004) Cine-MRI assessment of cardiac function in mice anesthetized with ketamine/xylazine and isoflurane. Magn Reson Mater Phys Biol Med 17(3–6):157–161

    Article  CAS  Google Scholar 

  37. You J, Wu J, Ge J et al (2012) Comparison between adenosine and isoflurane for assessing the coronary flow reserve in mouse models of left ventricular pressure and volume overload. Am J Physiol Heart Circ Physiol 303(10):H1199–H1207

    Article  CAS  PubMed  Google Scholar 

  38. Braunwald E (1971) Control of myocardial oxygen consumption: physiologic and clinical considerations. Am J Cardiol 27(4):416–432

    Article  CAS  PubMed  Google Scholar 

  39. Soler R, Rodríguez E, Monserrat L et al (2006) Magnetic resonance imaging of delayed enhancement in hypertrophic cardiomyopathy: relationship with left ventricular perfusion and contractile function. J Comput Assist Tomogr 30(3):412–420

    Article  PubMed  Google Scholar 

  40. Gould KL, Carabello BA (2003) Why angina in aortic stenosis with normal coronary arteriograms? Circulation 107(25):3121–3123

    Article  PubMed  Google Scholar 

  41. Gao X-M, Kiriazis H, Moore X-L et al (2005) Regression of pressure overload-induced left ventricular hypertrophy in mice. Am J Physiol Heart Circ Physiol 288(6):H2702–H2707

    Article  CAS  PubMed  Google Scholar 

  42. Kober F, Iltis I, Cozzone PJ et al (2005) Myocardial blood flow mapping in mice using high-resolution spin labeling magnetic resonance imaging: influence of ketamine/xylazine and isoflurane anesthesia. Magn Reson Med 53(3):601–606

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank L. Niesen, D. Veraart and J. Habets for biotechnical assistance and T. van Osch (Leiden University Medical Center) for discussions. This research was performed within the framework of the Center for Translational Molecular Medicine, project TRIUMPH (Grant 01C-103), and supported by the Netherlands Heart Foundation.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands

    Bastiaan J. van Nierop, Wouter J. R. Dijk, Klaas Nicolay & Gustav J. Strijkers

  2. Department of Radiology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands

    Bram F. Coolen

  3. Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands

    Noortje A. Bax

  4. Experimental Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands

    Elza D. van Deel & Dirk J. Duncker

Authors
  1. Bastiaan J. van Nierop
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bram F. Coolen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noortje A. Bax
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wouter J. R. Dijk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elza D. van Deel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dirk J. Duncker
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Klaas Nicolay
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gustav J. Strijkers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gustav J. Strijkers.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Nierop, B.J., Coolen, B.F., Bax, N.A. et al. Myocardial perfusion MRI shows impaired perfusion of the mouse hypertrophic left ventricle. Int J Cardiovasc Imaging 30, 619–628 (2014). https://doi.org/10.1007/s10554-014-0369-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-014-0369-0

Keywords

Search

Navigation