Skip to main content
Log in

Correlation of left ventricular wall thickness, heart mass, serological parameters and late gadolinium enhancement in cardiovascular magnetic resonance imaging of myocardial inflammation in an experimental animal model of autoimmune myocarditis

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

Abstract

For a definitive diagnosis of myocarditis, different strategies like analysis of late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR) up to invasive endomyocardial biopsy have been applied. The objective of the study was to investigate inflammatory changes like left ventricular wall thickening and increase of ventricular mass and to quantitatively analyse their correlation with extent and localisation of myocardial damage in CMR and with subsequent changes of serological markers in an animal model of an experimental autoimmune myocarditis (EAM). In the current study, an EAM was induced in 10 male Lewis rats, 10 rats served as control. On day 21, animals were examined with four CMR protocols to assess the extent of LGE in a 12 segment model of the rat heart. Left myocardial wall thickness and mass and histological grade of inflammation were measured to determine localisation and severity of the induced myocarditis. Depending on the CMR sequence, LGE was mostly found in the left anterior (9.6%) and left lateral (8.7%) myocardial wall segments. Wall thickness correlated with the LGE area in CMR imaging and the histopathological severity of myocarditis for the left lateral myocardial wall segment. In a similar way, the heart mass correlated to the extent of LGE for the left lateral segment. We conclude that in our animal model left ventricular wall thickness and mass reflect the severity of myocardial changes in myocarditis and that the EAM rat model is well suited for further investigations of myocarditis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Blauwet LA, Cooper LT (2010) Myocarditis. Prog Cardiovasc Dis 52(4):274–288

    Article  PubMed  Google Scholar 

  2. Cooper LT Jr (2009) Myocarditis. N Engl J Med 360(15):1526–1538

    Article  PubMed  CAS  Google Scholar 

  3. Doolan A, Langlois N, Semsarian C (2004) Causes of sudden cardiac death in young Australians. Med J Aust 180(3):110–112

    PubMed  Google Scholar 

  4. Magnani JW (2006) Myocarditis: current trends in diagnosis and treatment. Circulation 113(6):876–890

    Article  PubMed  Google Scholar 

  5. Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R, Hare J, Bricker JT, Bowles KR, Towbin JA (2003) Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol 42(3):466–472

    Article  PubMed  Google Scholar 

  6. Kawai C (1999) From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future. Circulation 99(8):1091–1100

    Article  PubMed  CAS  Google Scholar 

  7. Gutberlet M, Spors B, Thoma T, Bertram H, Denecke T, Felix R, Noutsias M, Schultheiss HP, Kühl U (2008) Suspected chronic myocarditis at cardiac MR: diagnostic accuracy and association with immunohistologically detected inflammation and viral persistence1. Radiology 246(2):401–409

    Article  PubMed  Google Scholar 

  8. Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT, White JA, Abdel-Aty H, Gutberlet M, Prasad S, Aletras A, Laissy JP, Paterson I, Filipchuk NG, Kumar A, Pauschinger M, Liu P, International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis (2009) Cardiovascular magnetic resonance in myocarditis: a JACC white paper. J Am Coll Cardiol 53(17):1475–1487

    Google Scholar 

  9. Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R (2007) The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, The American College of Cardiology, and the European Society Of Cardiology. Circulation 116(19):2216–2233

    Article  PubMed  Google Scholar 

  10. Lie JT (1988) Myocarditis and endomyocardial biopsy in unexplained heart failure: a diagnosis in search of a disease. Ann Intern Med 109(7):525–528

    PubMed  CAS  Google Scholar 

  11. Baccouche H, Mahrholdt H, Meinhardt G, Merher R, Voehringer M, Hill S, Klingel K, Kandolf R, Sechtem U, Yilmaz A (2009) Diagnostic synergy of non-invasive cardiovascular magnetic resonance and invasive endomyocardial biopsy in troponin-positive patients without coronary artery disease. Eur Heart J 30(23):2869–2879

    Article  PubMed  CAS  Google Scholar 

  12. Mahrholdt H (2004) Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology. Circulation 109(10):1250–1258

    Article  PubMed  Google Scholar 

  13. Cho JR, Park S, Choi BW, Kang S-M, Ha J-W, Chung N, Choe K-O, Cho S-Y, Rim S-J (2010) Delayed enhancement magnetic resonance imaging is a significant prognostic factor in patients with non-ischemic cardiomyopathy. Circ J 74(3):476–483

    Article  PubMed  Google Scholar 

  14. Abdel-Aty H, Boyé P, Zagrosek A, Wassmuth R, Kumar A, Messroghli D, Bock P, Dietz R, Friedrich MG, Schulz-Menger J (2005) Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches. J Am Coll Cardiol 45(11):1815–1822

    Article  PubMed  Google Scholar 

  15. Yelgec NS, Dymarkowski S, Ganame J, Bogaert J (2007) Value of MRI in patients with a clinical suspicion of acute myocarditis. Eur Radiol 17(9):2211–2217

    Article  PubMed  Google Scholar 

  16. Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ (2005) Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J 26(15):1461–1474

    Article  PubMed  Google Scholar 

  17. Stork A, Müllerleile K, Bansmann P, Koops A, Meinertz T, Adam G, Lund G (2007) Muster der späten Kontrastmittelanreicherung in der MRT bei ischämischen und nicht-ischämischen Kardiomyopathien. Fortschr Röntgenstr 179(1):21–30

    Article  CAS  Google Scholar 

  18. Mahrholdt H, Wagner A, Deluigi CC, Kispert E, Hager S, Meinhardt G, Vogelsberg H, Fritz P, Dippon J, Bock CT, Klingel K, Kandolf R, Sechtem U (2006) Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation 114(15):1581–1590

    Article  PubMed  Google Scholar 

  19. Kodama M, Matsumoto Y, Fujiwara M, Masani F, Izumi T, Shibata A (1990) A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction. Clin Immunol Immunopathol 57(2):250–262

    Article  PubMed  CAS  Google Scholar 

  20. Izumi T, Takehana H, Matsuda C, Yokoyama H, Kohno K, Suzuki K, Inomata T (2000) Experimental autoimmune myocarditis and its pathomechanism. Herz 25(3):274–278

    Article  PubMed  CAS  Google Scholar 

  21. Izumi T, Kodama M, Shibata A (1991) Experimental giant cell myocarditis induced by cardiac myosin immunization. Eur Heart J 12(Suppl D):166–168

    PubMed  Google Scholar 

  22. Veeraveedu PT, Watanabe K, Ma M, Palaniyandi SS, Yamaguchi K, Suzuki K, Kodama M, Aizawa Y (2008) Torasemide, a long-acting loop diuretic, reduces the progression of myocarditis to dilated cardiomyopathy. Eur J Pharmacol 581(1–2):121–131

    Article  PubMed  CAS  Google Scholar 

  23. Kodama M, Matsumoto Y, Fujiwara M, Zhang SS, Hanawa H, Itoh E, Tsuda T, Izumi T, Shibata A (1991) Characteristics of giant cells and factors related to the formation of giant cells in myocarditis. Circ Res 69(4):1042–1050

    Article  PubMed  CAS  Google Scholar 

  24. Korkusuz H, Esters P, Naguib N, Nour Eldin NE, Lindemayr S, Huebner F, Koujan A, Bug R, Ackermann H, Vogl TJ (2009) Acute myocarditis in a rat model: late gadolinium enhancement with histopathological correlation. Eur Radiol 19(11):2672–2678

    Article  PubMed  Google Scholar 

  25. Newby LK (2004) Markers of cardiac ischemia, injury, and inflammation. Prog Cardiovasc Dis 46(5):404–416

    Article  PubMed  Google Scholar 

  26. Bleuel H, Deschl U, Bertsch T, Bölz G, Rebel W (1995) Diagnostic efficiency of troponin T measurements in rats with experimental myocardial cell damage. Exp Toxicol Pathol 47(2–3):121–127

    Article  PubMed  CAS  Google Scholar 

  27. Giffen PS, Turton J, Andrews CM, Barrett P, Clarke CJ, Fung K-W, Munday MR, Roman IF, Smyth R, Walshe K, York MJ (2003) Markers of experimental acute inflammation in the Wistar Han rat with particular reference to haptoglobin and C-reactive protein. Arch Toxicol 77(7):392–402

    Article  PubMed  CAS  Google Scholar 

  28. Davies LA, Hamilton DL, Hopkins PM, Boyett MR, Harrison SM (1999) Concentration-dependent inotropic effects of halothane, isoflurane and sevoflurane on rat ventricular myocytes. Br J Anaesth 82(5):723–730

    Article  PubMed  CAS  Google Scholar 

  29. Gilson WD, Kraitchman DL (2007) Cardiac magnetic resonance imaging in small rodents using clinical 1.5 T and 3.0 T scanners. Methods 43(1):35–45

    Article  PubMed  CAS  Google Scholar 

  30. Klug G, Trieb T, Schocke M, Nocker M, Skalla E, Mayr A, Nowosielski M, Pedarnig K, Bartel T, Moes N, Pachinger O, Metzler B (2009) Quantification of regional functional improvement of infarcted myocardium after primary PTCA by contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging 29(2):298–304

    Article  PubMed  Google Scholar 

  31. Yuan Z, Liu Y, Liu Y, Zhang J, Kishimoto C, Ma A, Liu Z (2004) Peroxisome proliferator-activated receptor-gamma ligands ameliorate experimental autoimmune myocarditis associated with inhibition of self-sensitive T cells. J Cardiovasc Pharmacol 43(6):868–875

    Article  PubMed  CAS  Google Scholar 

  32. Kanda T, Takahashi T, Kudo S, Takeda T, Tsugawa H, Takekoshi N (2004) Leptin deficiency enhances myocardial necrosis and lethality in a murine model of viral myocarditis. Life Sci 75(12):1435–1447

    Article  PubMed  CAS  Google Scholar 

  33. Korkusuz H, Esters P, Huebner F, Bug R, Ackermann H, Vogl TJ (2010) Accuracy of cardiovascular magnetic resonance in myocarditis: comparison of MR and histological findings in an animal model. J Cardiovasc Magn Reson 12(1):49

    Article  PubMed  Google Scholar 

  34. Skouri HN, Dec GW, Friedrich MG, Cooper LT (2006) Noninvasive imaging in myocarditis. J Am Coll Cardiol 48(10):2085–2093

    Article  PubMed  Google Scholar 

  35. Chow LH, Radio SJ, Sears TD, McManus BM (1989) Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. J Am Coll Cardiol 14(4):915–920

    Article  PubMed  CAS  Google Scholar 

  36. De Cobelli F, Pieroni M, Esposito A, Chimenti C, Belloni E, Mellone R, Canu T, Perseghin G, Gaudio C, Maseri A, Frustaci A, Del Maschio A (2006) Delayed gadolinium-enhanced cardiac magnetic resonance in patients with chronic myocarditis presenting with heart failure or recurrent arrhythmias. J Am Coll Cardiol 47(8):1649–1654

    Google Scholar 

  37. Kim RJ, Choi KM, Judd RM (2003) Assessment of myocardial viability by contrast enhancement. In: Higgins CB, Roos AD (eds) Cardiovascular MRI and MRA. Lippincott, Philadelphia, pp 209–237

    Google Scholar 

  38. Friedrich MG, Abdel-Aty H, Taylor A, Schulz-Menger J, Messroghli D, Dietz R (2008) The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance. J Am Coll Cardiol 51(16):1581–1587

    Article  PubMed  Google Scholar 

  39. Li G, Xiang B, Dai G, Shaw A, Liu H, Yang B, Jackson M, Deslauriers R, Tian G (2005) Tissue edema does not change gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced T1 relaxation times of viable myocardium. J Magn Reson Imaging 21(6):744–751

    Article  PubMed  Google Scholar 

  40. Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM (1999) Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 100(19):1992–2002

    Article  PubMed  CAS  Google Scholar 

  41. Karamitsos TD, Francis JM, Myerson S, Selvanayagam JB, Neubauer S (2009) The role of cardiovascular magnetic resonance imaging in heart failure. J Am Coll Cardiol 54(15):1407–1424

    Article  PubMed  Google Scholar 

  42. Casolo G, Minneci S, Manta R, Sulla A, Del Meglio J, Rega L, Gensini G (2006) Identification of the ischemic etiology of heart failure by cardiovascular magnetic resonance imaging: diagnostic accuracy of late gadolinium enhancement. Am Heart J 151(1):101–108

    Article  PubMed  Google Scholar 

  43. Bohl S, Wassmuth R, Abdel-Aty H, Rudolph A, Messroghli D, Dietz R, Schulz-Menger J (2008) Delayed enhancement cardiac magnetic resonance imaging reveals typical patterns of myocardial injury in patients with various forms of non-ischemic heart disease. Int J Cardiovasc Imaging 24(6):597–607

    Article  PubMed  Google Scholar 

  44. Felker GM, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Baughman KL, Hare JM (2000) Echocardiographic findings in fulminant and acute myocarditis. J Am Coll Cardiol 36(1):227–232

    Article  PubMed  CAS  Google Scholar 

  45. Maeder M, Wolber T, Rickli H, Ammann P (2006) Transient left ventricular „hypertrophy“ in a woman with meningoencephalitis. Echocardiography 23(7):582–584

    Article  PubMed  Google Scholar 

  46. Hiramitsu S, Morimoto S, Kato S, Uemura A, Kubo N, Kimura K, Sugiura A, Itoh T, Hishida H (2001) Transient ventricular wall thickening in acute myocarditis: a serial echocardiographic and histopathologic study. Jpn Circ J 65(10):863–866

    Article  PubMed  CAS  Google Scholar 

  47. Zagrosek A, Wassmuth R, Abdel-Aty H, Rudolph A, Dietz R, Schulz-Menger J (2008) Relation between myocardial edema and myocardial mass during the acute and convalescent phase of myocarditis–a CMR study. J Cardiovasc Magn Reson 10(1):19–26

    Article  PubMed  Google Scholar 

  48. Lauer B, Niederau C, Kühl U, Schannwell M, Pauschinger M, Strauer BE, Schultheiss HP (1997) Cardiac troponin T in patients with clinically suspected myocarditis. J Am Coll Cardiol 30(5):1354–1359

    Article  PubMed  CAS  Google Scholar 

  49. Munk PS, Manhenke C, Ørn S, Greve OJ (2008) Contrast-enhanced cardiac magnetic resonance in patients with acute myocarditis. Tidsskr Nor Laegeforen 128(10):1172–1174

    PubMed  Google Scholar 

  50. Friedrich MG, Strohm O, Schulz-Menger J, Marciniak H, Luft FC, Dietz R (1998) Contrast media–enhanced magnetic resonance imaging visualizes myocardial changes in the course of viral myocarditis. Circulation 97(18):1802–1809

    Article  PubMed  CAS  Google Scholar 

  51. Shanes JG, Ghali J, Billingham ME, Ferrans VJ, Fenoglio JJ, Edwards WD, Tsai CC, Saffitz JE, Isner J et al (1987) Interobserver variability in the pathologic interpretation of endomyocardial biopsy results. Circulation 75(2):401–405

    Article  PubMed  CAS  Google Scholar 

  52. Wojnicz R, Nowalany-Kozielska E, Wodniecki J, Szczurek-Katański K, Nozyński J, Zembala M, Rozek MM (1998) Immunohistological diagnosis of myocarditis. Potential role of sarcolemmal induction of the MHC and ICAM-1 in the detection of autoimmune mediated myocyte injury. Eur Heart J 19(10):1564–1572

    Article  PubMed  CAS  Google Scholar 

  53. Noutsias M, Pankuweit S, Maisch B (2009) Biomarkers in inflammatory and noninflammatory cardiomyopathy. Herz 34(8):614–623

    Article  PubMed  Google Scholar 

  54. Shah DJ, Judd RM, Kim RJ (2006) Myocardial Viability. In: Edelman RR, Hesselink JR, Zlatkin MB et al (eds) Clinical magnetic resonance imaging, 3rd edn. Elsevier, New York, p 992

    Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wolfgang Kromen.

Additional information

Wolfgang Kromen and Huedayi Korkusuz contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kromen, W., Korkusuz, H., Korkusuz, Y. et al. Correlation of left ventricular wall thickness, heart mass, serological parameters and late gadolinium enhancement in cardiovascular magnetic resonance imaging of myocardial inflammation in an experimental animal model of autoimmune myocarditis. Int J Cardiovasc Imaging 28, 1983–1997 (2012). https://doi.org/10.1007/s10554-012-0020-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-012-0020-x

Keywords

Navigation