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.
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Blauwet LA, Cooper LT (2010) Myocarditis. Prog Cardiovasc Dis 52(4):274–288
Cooper LT Jr (2009) Myocarditis. N Engl J Med 360(15):1526–1538
Doolan A, Langlois N, Semsarian C (2004) Causes of sudden cardiac death in young Australians. Med J Aust 180(3):110–112
Magnani JW (2006) Myocarditis: current trends in diagnosis and treatment. Circulation 113(6):876–890
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
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
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
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
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
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
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
Mahrholdt H (2004) Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology. Circulation 109(10):1250–1258
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
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
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
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
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
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
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
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
Izumi T, Kodama M, Shibata A (1991) Experimental giant cell myocarditis induced by cardiac myosin immunization. Eur Heart J 12(Suppl D):166–168
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
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
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
Newby LK (2004) Markers of cardiac ischemia, injury, and inflammation. Prog Cardiovasc Dis 46(5):404–416
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
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
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
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
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
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
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
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
Skouri HN, Dec GW, Friedrich MG, Cooper LT (2006) Noninvasive imaging in myocarditis. J Am Coll Cardiol 48(10):2085–2093
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
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
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
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
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
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
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
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
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
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
Maeder M, Wolber T, Rickli H, Ammann P (2006) Transient left ventricular „hypertrophy“ in a woman with meningoencephalitis. Echocardiography 23(7):582–584
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
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
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
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
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
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
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
Noutsias M, Pankuweit S, Maisch B (2009) Biomarkers in inflammatory and noninflammatory cardiomyopathy. Herz 34(8):614–623
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
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Wolfgang Kromen and Huedayi Korkusuz contributed equally to this work.
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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
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DOI: https://doi.org/10.1007/s10554-012-0020-x