Alterations in creatine metabolism observed in experimental autoimmune myocarditis using ex vivo proton magic angle spinning MRS |
| |
| Authors: | Frédéric Muench Joren Retel Sarah Jeuthe Darach O h‐Ici Barth van Rossum Katharina Wassilew Patrick Schmerler Titus Kuehne Felix Berger Hartmut Oschkinat Daniel R. Messroghli |
| |
| Affiliation: | 1. German Heart Institute Berlin, Department of Congenital Heart Disease and Pediatric Cardiology, Berlin, Germany;2. Leibniz Institute for Molecular Pharmacology, Department of NMR‐Supported Structural Biology, Berlin, Germany;3. German Heart Institute Berlin, Cardiovascular Pathology, Berlin, Germany;4. Charité‐University Medicine, Center for Cardiovascular Research, Berlin, Germany;5. German Heart Institute Berlin, Department of Internal Medicine – Cardiology, Berlin, Germany |
| |
| 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 (1H‐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 (1H‐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 1H‐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 1H‐MRS correlates with LVEF and is able to differentiate between healthy myocardium and myocardium from rats with EAM. Copyright © 2015 John Wiley & Sons, Ltd. |
| |
| Keywords: | myocarditis experimental autoimmune myocarditis MRS cardiac metabolism myocardial injury creatine |
|
|
