title: Alterations in creatine metabolism observed in experimental autoimmune myocarditis using ex vivo proton magic angle spinning MRS.
abstract: Experimental autoimmune myocarditis (EAM) in rodents is an accepted model of myocarditis and dilated cardiomyopathy (DCM). Altered metabolism is thought to play an important role in the pathogenesis of DCM and heart failure (HF). Study of the metabolism may provide new diagnostic information and insights into the mechanisms of myocarditis and HF. Proton MRS ((1)H-MRS) has not yet been used to study the changes occurring in myocarditis and subsequent HF. We aimed to explore the changes in creatine metabolism using this model and compare them with the findings in healthy animals. Myocardial function of male young Lewis rats with EAM was quantified by performing left ventricular ejection fraction (LVEF) analysis in short-axis cine images throughout the whole heart. Inflammatory cellular infiltrate was assessed by immunohistochemistry. Myocardial tissue was analyzed using ex vivo proton magic angle spinning MRS ((1)H-MAS-MRS). Myocarditis was confirmed histologically by the presence of an inflammatory cellular infiltrate and CD68 positive staining. A significant increase in the metabolic ratio of Tau/tCr (taurine/total creatine) obtained by (1)H-MAS-MRS was observed in myocarditis compared with healthy controls (21 d acute EAM, 4.38 (±0.23); 21 d control, 2.84 (±0.08); 35 d chronic EAM, 4.47 (±0.83); 35 d control, 2.59 (±0.38); P < 0.001). LVEF was reduced in diseased animals (EAM, 55.2% (±11.3%); control, 72.6% (±3.8%); P < 0.01) and correlated with Tau/tCr ratio (R = 0.937, P < 0.001). Metabolic alterations occur acutely with the development of myocarditis. Myocardial Tau/tCr ratio as detected by (1)H-MRS correlates with LVEF and is able to differentiate between healthy myocardium and myocardium from rats with EAM.
authors.affiliation: German Heart Institute Berlin, Department of Congenital Heart Disease and Pediatric Cardiology, Berlin, Germany.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Muench
authors.affiliation: Leibniz Institute for Molecular Pharmacology, Department of NMR-Supported Structural Biology, Berlin, Germany.
authors.forename: Joren
authors.initials: J
authors.lastname: Retel
authors.affiliation: German Heart Institute Berlin, Department of Congenital Heart Disease and Pediatric Cardiology, Berlin, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jeuthe
authors.affiliation: German Heart Institute Berlin, Department of Congenital Heart Disease and Pediatric Cardiology, Berlin, Germany.
authors.forename: Darach
authors.identifier: http://orcid.org/0000-0003-1280-6979
authors.initials: D
authors.lastname: O h-Ici
authors.affiliation: Leibniz Institute for Molecular Pharmacology, Department of NMR-Supported Structural Biology, Berlin, Germany.
authors.forename: Barth
authors.initials: B
authors.lastname: van Rossum
authors.affiliation: German Heart Institute Berlin, Cardiovascular Pathology, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wassilew
authors.affiliation: Charité-University Medicine, Center for Cardiovascular Research, Berlin, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schmerler
authors.affiliation: German Heart Institute Berlin, Department of Congenital Heart Disease and Pediatric Cardiology, Berlin, Germany.
authors.forename: Titus
authors.initials: T
authors.lastname: Kuehne
authors.affiliation: German Heart Institute Berlin, Department of Congenital Heart Disease and Pediatric Cardiology, Berlin, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Berger
authors.affiliation: Leibniz Institute for Molecular Pharmacology, Department of NMR-Supported Structural Biology, Berlin, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Oschkinat
authors.affiliation: German Heart Institute Berlin, Department of Congenital Heart Disease and Pediatric Cardiology, Berlin, Germany.|German Heart Institute Berlin, Department of Internal Medicine - Cardiology, Berlin, Germany.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Messroghli
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism*; D008297:Male; D009205:Myocarditis / Q000175:diagnosis / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013113:Spin Labels; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D013113:Spin Labels; D016875:tau Proteins; D003401:Creatine
keywords: MRS; cardiac metabolism; creatine; experimental autoimmune myocarditis; myocardial injury; myocarditis