Muench Frédéric, Retel Joren, Jeuthe Sarah, O h-Ici Darach, van Rossum Barth, Wassilew Katharina, Schmerler Patrick, Kuehne Titus, Berger Felix, Oschkinat Hartmut, Messroghli Daniel R
German Heart Institute Berlin, Department of Congenital Heart Disease and Pediatric Cardiology, Berlin, Germany.
Leibniz Institute for Molecular Pharmacology, Department of NMR-Supported Structural Biology, Berlin, Germany.
NMR Biomed. 2015 Dec;28(12):1625-33. doi: 10.1002/nbm.3415. Epub 2015 Oct 7.
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.
啮齿动物实验性自身免疫性心肌炎（EAM）是心肌炎和扩张型心肌病（DCM）公认的模型。代谢改变被认为在DCM和心力衰竭（HF）的发病机制中起重要作用。对代谢的研究可能为心肌炎和HF的机制提供新的诊断信息和见解。质子磁共振波谱（(1)H-MRS）尚未用于研究心肌炎及后续HF中发生的变化。我们旨在利用该模型探索肌酸代谢的变化，并将其与健康动物的研究结果进行比较。通过对整个心脏短轴电影图像进行左心室射血分数（LVEF）分析，对患有EAM的雄性年轻Lewis大鼠的心肌功能进行量化。通过免疫组织化学评估炎性细胞浸润。使用离体质子魔角旋转磁共振波谱（(1)H-MAS-MRS）分析心肌组织。通过炎性细胞浸润和CD68阳性染色在组织学上证实了心肌炎。与健康对照组相比，在心肌炎中观察到通过(1)H-MAS-MRS获得的Tau/tCr（牛磺酸/总肌酸）代谢比值显著增加（21天急性EAM，4.38（±0.23）；21天对照组，2.84（±0.08）；35天慢性EAM，4.47（±0.83）；35天对照组，2.59（±0.38）；P < 0.001）。患病动物的LVEF降低（EAM，55.2%（±11.3%）；对照组，72.6%（±3.8%）；P < 0.01），且与Tau/tCr比值相关（R = 0.937，P < 0.001）。随着心肌炎的发展，代谢改变会急性发生。通过(1)H-MRS检测到的心肌Tau/tCr比值与LVEF相关，并且能够区分健康心肌和患有EAM大鼠的心肌。
