Skip to main content
SpringerLink
Log in

Assessment of the early stage of cardiac remodeling of spontaneously hypertensive heart failure rats using the quantitative 3-dimensional analysis provided by acipimox-enhanced FDG-PET

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

Abstract

Spontaneously hypertensive heart failure rats (SHHF) appear to constitute an original model for analyzing the evolution of the metabolic syndrome towards heart failure. This study aimed to characterize early cardiac dysfunction and remodeling in SHHF rats: (1) as compared with spontaneously hypertensive rats (SHR) and with a control group of Kyoto rats (WKY), and (2) by using the 3-dimensional quantitative analysis provided by acipimox-enhanced positron emission tomography (PET) with 18F-fluorodesoxyglucose (FDG). Left ventricular (LV) ejection fraction (EF) and volume were quantified by automatic software on the FDG-PET images recorded in SHR (n = 20), SHHF (n = 18) and WKY-rats (n = 19) at ages 3 or 10 months old. Arterial blood pressure was determined by cardiac catheterization and cardiac fibrosis was quantified after sacrifice. Blood pressure was similarly elevated in SHR and SHHF rats (respective systolic blood pressures at 10-months: 199 ± 39 vs. 205 ± 2 mmHg), but SHHF rats had higher body mass than SHR rats (at 10-months, 630 ± 36 vs. 413 ± 27 g, p < 0.05) and higher blood levels of cholesterol and of triglycerides. At 3 months, cardiac parameters did not show significant differences between groups but at 10-months, SHHF and SHR rats exhibited an enhancement in myocardial mass and fibrosis associated with a clear decline in LV-EF (SHHF: 46 ± 6 %; SHR: 47 ± 5 %) as compared with WKY (56 ± 6 %, p < 0.01 for both comparisons). Cardiac remodeling of SHHF rats was clearly observable by FDG-PET from the age of 10-months, but in a similar way to that observed for SHR rats, suggesting a predominant role of hypertension.

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

Similar content being viewed by others

References

  1. Schillaci G, Pirro M, Vaudo G, Gemelli F, Marchesi S, Porcellati C, Mannarino E (2004) Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 43:1817–1822

    Article  PubMed  Google Scholar 

  2. McCune SA, Baker PB, Stills JHF (1990) SHHF/Mcc-cp rat: model of obesity, non-insulin-dependent diabetes, and congestive heart failure. ILAR News 32:23–27

    Article  Google Scholar 

  3. Saliaris AP, Amado LC, Minhas KM, Schuleri KH, Lehrke S, St John M, Fitton T, Barreiro C, Berry C, Zheng M, Kozielski K, Eneboe V, Brawn J, Hare JM (2007) Chronic allopurinol administration ameliorates maladaptive alterations in Ca2+ cycling proteins and beta adrenergic hyporesponsiveness in heart failure. Am J Physiol Heart Circ Physiol 292(3):H1328–H1335

    Article  CAS  PubMed  Google Scholar 

  4. Haas GJ, McCune SA, Brown DM, Cody RJ (1995) Echocardiographic characterization of left ventricular adaptation in a genetically determined heart failure rat model. Am Heart J 130:806–811

    Article  CAS  PubMed  Google Scholar 

  5. Johnsen D, Kacimi R, Anderson BE, Thomas TA, Said S, Gerdes MA (2005) Protein kinase C isozymes in hypertension and hypertrophy: insight from SHHF rat hearts. Mol Cell Biochem 270:63–69

    Article  CAS  PubMed  Google Scholar 

  6. Anderson KM, Eckhart AD, Willette RN, Koch WJ (1999) The myocardial beta-adrenergic system in spontaneously hypertensive heart failure (SHHF) rats. Hypertension 33:402–407

    Article  CAS  PubMed  Google Scholar 

  7. Sridhar A, Dech SJ, Lacombe VA, Elton TS, McCune SA, Altschuld RA, Carnes CA (2006) Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats. Am J Physiol Heart Circ Physiol 291:2192–2198

    Article  Google Scholar 

  8. Tamura T, Onodera T, Said S, Gerdes AM (1998) Correlation of myocyte lengthening to chamber dilation in the spontaneously hypertensive heart failure (SHHF) rat. J Mol Cell Cardiol 30:2175–2181

    Article  CAS  PubMed  Google Scholar 

  9. Heyen JR, Blasi ER, Nikula K, Rocha R, Daust HA, Frierdich G, Van Vleet JF, De Ciechi P, McMahon EG, Rudolph AE (2002) Structural, functional, and molecular characterization of the SHHF model of heart failure. Am J Physiol Heart Circ Physiol 283:1775–1784

    Google Scholar 

  10. Schultz RL, Swallow JG, Waters RP, Kuzman JA, Redetzke RA, Said S, De Escobar GM, Gerdes AM (2007) Effects of excessive long-term exercise on cardiac function and myocyte remodelling in hypertensive heart failure rats. Hypertension 50:410–416

    Article  CAS  PubMed  Google Scholar 

  11. Poussier S, Maskali F, Tran N, Person C, Maureira P, Boutley H, Karcher G, Lacolley P, Régnault V, Fay R, Marie PY (2010) ECG-triggered 18F-fluorodeoxyglucose positron emission tomography imaging of the rat heart is dramatically enhanced by acipimox. Eur J Nucl Med Mol Imaging 37:1745–1750

    Article  PubMed  Google Scholar 

  12. Bousquenaud M, Maskali F, Poussier S, Marie PY, Boutley H, Karcher G, Wagner DR, Devaux Y (2012) Acipimox-enhanced (18F)-fluorodeoxyglucose positron emission tomography for characterizing and predicting early remodeling in the rat infarct model. Int J Cardiovasc Imaging 28(6):1407–1415

    Google Scholar 

  13. Bousquenaud M, Maskali F, Poussier S, Zangrando J, Marie PY, Boutley H, Fay R, Karcher G, Wagner DR, Devaux Y (2013) Cardioprotective effects of adenosine within the border and remote areas of myocardial infarction. EJNMMI Res 3(1):65

    Article  PubMed Central  PubMed  Google Scholar 

  14. Maskali F, Franken PR, Poussier S, Tran N, Vanhove C, Boutley H, Le Gall H, Karcher G, Zannad F, Lacolley P, Marie PY (2006) Initial infarct size predicts subsequent cardiac remodeling in the rat infarct model: an in vivo serial pinhole gated SPECT study. J Nucl Med 47(2):337–344

    PubMed  Google Scholar 

  15. Lacolley P, Labat C, Pujol A, Delcayre C, Benetos A, Safar M (2002) Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone. Circulation 106:2848–2853

    Article  CAS  PubMed  Google Scholar 

  16. Sloboda N, Fève B, Thornton SN, Nzietchueng R, Regnault V, Simon G, Labat C, Louis H, Max JP, Muscat A, Osborne-Pellegrin M, Lacolley P, Benetos A (2012) Fatty acids impair endothelium-dependent vasorelaxation: a link between obesity and arterial stiffness in very old Zucke rats. J Gerontol A Biol Sci Med Sci 67(9):927–938

    Article  PubMed  Google Scholar 

  17. Maskali F, Poussier S, Marie PY, Tran N, Antunes L, Olivier P, Plenat F, Maîtrejean S, Zannad F, Karcher G (2005) High-resolution simultaneous imaging of SPECT, PET, and MRI tracers on histologic sections of myocardial infarction. J Nucl Cardiol 12(2):229–230

    Article  PubMed  Google Scholar 

  18. Reffelmann T, Kloner RA (2003) Transthoracic echocardiography in rats. Evaluation of commonly used indices of left ventricular dimensions, contractile performance, and hypertrophy in a genetic model of hypertrophic heart failure (SHHF-Mcc-facp-Rats) in comparison with Wistar rats during aging. Basic Res Cardiol 98:275–284

    Article  PubMed  Google Scholar 

  19. Poornima I, Brown SB, Bhashyam S, Parikh P, Bolukoglu H, Shannon RP (2008) Chronic glucagon-like peptide-1 infusion sustains left ventricular systolic function and prolongs survival in the spontaneously hypertensive, heart failure-prone rat. Circ Heart Fail 1:153–160

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Arias T, Chen J, Fayad ZA, Fuster V, Hajjar RJ, Chemaly ER (2013) Comparison of echocardiographic measurements of left ventricular volumes to full volume magnetic resonance imaging in normal and diseased rats. J Am Soc Echocardiogr 26(8):910–918

    Article  PubMed  Google Scholar 

  21. Richardson JD, Bertaso AG, Frost L, Psaltis PJ, Carbone A, Koschade B, Wong DT, Nelson AJ, Paton S, Williams K, Azarisman S, Worthley MI, Teo KS, Gronthos S, Zannettino AC, Worthley SG (2013) Cardiac magnetic resonance, transthoracic and transoesophageal echocardiography: a comparison of in vivo assessment of ventricular function in rats. Lab Anim 47(4):291–300

    Article  CAS  PubMed  Google Scholar 

  22. Linz D, Hohl M, Mahfoud F, Reil JC, Linz W, Hübschle T, Juretschke HP, Neumann-Häflin C, Rütten H, Böhm M (2012) Cardiac remodelling and myocardial dysfunction in obese spontaneously hypertensive rats. J Transl Med 10(10):187

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Oliveira Junior SA, Dal Pai-Silva M, Martinez PF, Lima-Leopoldo AP, Campos DH, Leopoldo AS, Okoshi MP, Okoshi K, Padovani CR, Cicogna AC (2010) Diet-induced obesity causes metabolic, endocrine and cardiac alterations in spontaneously hypertensive rats. Med Sci Monit 16 (12):BR367-73

  24. Gómez-Garre D, González-Rubio ML, Muñoz-Pacheco P, Caro-Vadillo A, Aragoncillo P, Fernández-Cruz A (2010) Rosuvastatin added to standard heart failure therapy improves cardiac remodelling in heart failure rats with preserved ejection fraction. Eur J Heart Fail 12:903–912

    Article  PubMed  Google Scholar 

  25. Cittadini A, Napoli R, Monti MG, Rea D, Longobardi S, Netti PA, Walser M, Samà M, Aimaretti G, Isgaard J, Saccà L (2012) Metformin prevents the development of chronic heart failure in the SHHF rat model. Diabetes 61:944–953

    Article  CAS  PubMed  Google Scholar 

  26. Hasegawa S, Kusuoka H, Uehara T, Yamaguchi H, Hori M, Nishimura T (1998) Glucose tolerance and myocardial F-18 fluorodeoxyglucose uptake in normal regions in coronary heart disease patients. Ann Nucl Med 12(6):363–368

    Article  CAS  PubMed  Google Scholar 

  27. Mäki M, Nuutila P, Laine H, Voipio-Pulkki LM, Haaparanta M, Solin O, Knuuti JM (1997) Myocardial glucose uptake in patients with NIDDM and stable coronary artery disease. Diabetes 46(9):1491–1496

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None

Author information

Authors and Affiliations

  1. GIE-Nancyclotep, CHU-Nancy, 5, rue du Morvan, 54000, Vandoeuvre-les-Nancy, France

    Fatiha Maskali, Sylvain Poussier, Henri Boutley, Mickael Lhuillier, Gilles Karcher & Pierre Y. Marie

  2. Faculty of Medicine, University of Lorraine, 54000, Nancy, France

    Sylvain Poussier, Henri Boutley & Gilles Karcher

  3. INSERM UMR 1116, 54000, Nancy, France

    Huguette Louis, Simon N. Thornton, Patrick Lacolley & Pierre Y. Marie

Authors
  1. Fatiha Maskali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sylvain Poussier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huguette Louis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henri Boutley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mickael Lhuillier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Simon N. Thornton
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gilles Karcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Patrick Lacolley
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pierre Y. Marie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fatiha Maskali.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maskali, F., Poussier, S., Louis, H. et al. Assessment of the early stage of cardiac remodeling of spontaneously hypertensive heart failure rats using the quantitative 3-dimensional analysis provided by acipimox-enhanced FDG-PET. Int J Cardiovasc Imaging 30, 449–456 (2014). https://doi.org/10.1007/s10554-013-0350-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-013-0350-3

Keywords

Search

Navigation