IL-18、IL-12及相关因子在大鼠实验性自身免疫心肌炎心肌中的表达时程和特征

目的:探讨IL-18、IL-12及相关细胞因子在大鼠实验性自身免疫心肌炎(EAM)心肌中的表达时程和特征。方法:以猪心脏肌球蛋白加等体积弗氏完全佐剂,辅结核杆菌H37Ra株之乳液为抗原,于Lewis大鼠双后肢皮下注射造模(EAM);用胶原酶灌流和网筛过滤法分离纯化心肌细胞;经免疫组化技术评估心肌损伤程度;按实时荧光定量法测急性期和慢性期,IL-18、IL-12及相关因子(IL-18R,IL-18RAcPL,IL-18BP以及IL-12p40,IL-12p35,IL-12Rβ1,IL-12Rβ2)mRNA表达情况。结果:IL-18、IL-12及相关因子表达主要在急性期,免疫后2周表达增多并达峰值(P<0.01,与正常对照组比较),4周后减少,并与EAM病程正相关;IL-18、IL-12及相关因子主要在巨噬细胞表达,其受体复合物在αβT细胞表达;慢性期仅IL-18BP在心肌细胞有表达。结论:IL-18、IL-12及相关因子参与EAM病理过程,各因子主要集中于急性期巨噬细胞和αβT细胞表达。     

静脉注射IL-19重组质粒对大鼠实验性自身免疫性心肌炎的治疗作用

目的:评估静脉注射白细胞介素19(interleukin-19,IL-19)重组质粒对大鼠实验性自身免疫性心肌炎(experimentalautoimmunemyocarditis,EAM)的治疗作用。方法:将猪心室肌球蛋白与等体积完全弗氏免疫佐剂充分混匀后,双足皮下注射制作大鼠EAM模型,免疫后第6天应用静脉注射方法将IL-19重组质粒导入体内,第17天行心脏超声检查后处死大鼠,检测心脏重量与体重比值、病理学评估、心肌炎面积率;实时荧光定量PCR检测心衰标记物心房钠尿肽(atrialnatriureticpeptide,ANP)、脑钠尿肽(brainnatriureticpeptide,BNP)的表达水平,进一步检测心肌相关炎症因子IL-18、IL-1β、IL-12p35和IFN-γ的表达水平。结果:IL-19重组质粒导入组的大鼠心功能得到显著改善;心脏重量体重比、心肌炎面积率、ANP、BNP的表达均较模型组明显下降;相关炎症细胞因子的表达也显著降低。结论:应用静脉注射法进行IL-19重组质粒体内导入治疗,明显抑制大鼠实验性自身免疫性心肌炎的炎症反应,减轻了心肌损伤从而改善心功能。     

大鼠自身免疫性心肌炎模型的建立

目的: 建立Lewis大鼠实验性自身免疫性心肌炎模型。方法: 从猪心中获得心肌肌凝蛋白,以此蛋白免疫Lewis大鼠,建立自身免疫性心肌炎模型，于初次免疫后第18 d、30 d、49 d进行心脏超声及血流动力学检查，ELISA法检测血清细胞因子，取心肌组织进行组织病理学检查。结果: 心脏超声及血流动力学检查显示，免疫组鼠心功能明显低于正常对照组，以第18 d最明显。血清学检查显示IFN-γ和IL-2水平在急性期达到高峰，IL-6、IL-10水平则在恢复期达到高峰。心脏病理检查显示，初次免疫后18 d，免疫组鼠全部出现明显的心肌炎病理改变。HE染色显示初次免疫后21 d大量炎性细胞浸润，伴有心肌的坏死，第30 d炎性细胞有所减少，第49 d炎性细胞基本消失。Massine trichrome染色显示炎症区域逐渐由纤维组织代替。结论: 猪心肌肌凝蛋白可以诱导Lewis大鼠出现典型的自身免疫性心肌炎，炎症损伤在心肌炎的发生和发展中起重要作用，参与了心功能紊乱和心室重构过程。     

TNF-α和cTnI在BALB/c小鼠自身免疫性心肌炎模型的动态变化

目的：以包含心肌球蛋白致病性抗原表位的人工合成多肽免疫BALB／c小鼠，建立实验性自身免疫性心肌炎动物模型，观察其自身免疫阶段和慢性病变期的病理变化，检测炎性因子和自身抗体变化。方法：人工合成含心肌肌球蛋白抗原重链表位长度为30个氨基酸残基的多肽0．8mg，纯化多肽皮下免疫遗传易感BALB／c小鼠，建立自身免疫性心肌炎模型，检测TNF—α和cTnl病变期间的改变。结果：实验组小鼠出现自身免疫性心肌炎病理改变。第14d出现心肌损伤，至第21d～30d心肌损伤达高峰，60d趋向稳定。心脏扩大，病理切片可见心肌层充血，间质巨噬细胞浸润明显，心肌细胞肿胀、逐步崩解坏死，被纤维组织取代。血清出现抗心肌肌球蛋白自身抗体阳性，并伴TNF—α和cTnl水平升高、高峰、下降的变化。结论：可成功诱导BALB／c系小鼠发病，建立实验性自身免疫性心肌炎动物模型，TNF—α和cTnl水平反映自身免疫性心肌炎病情发生、发展和转归。     

IL-1RⅡ重组质粒导入对大鼠实验性自身免疫性心肌炎的治疗作用

目的:评估编码Ⅱ型白细胞介素-1受体(typeⅡinterleukin-1receptor,IL-1RⅡ)的重组质粒在大鼠实验性自身免疫性心肌炎(experimentalautoimmunemyocarditis,EAM)中的治疗效果。方法:将猪心室肌球蛋白与等体积完全弗氏免疫佐剂充分混匀后,于第0dLewis大鼠双后足皮下注射制作EAM模型,第6d应用流体动力学方法进行重组质粒IL-1RⅡ的体内导入,第17d进行大鼠心脏超声检查后,处死大鼠,检测大鼠心/体重比值、心脏病理学评估及心肌炎面积率,进一步应用实时荧光定量RT-PCR检测心衰标记物脑钠尿肽(brainnatriureticpeptide,BNP)的水平。同时检测白细胞介素-1(interleukin-1,IL-1)相关因子白细胞介素-1β(interleukin-1beta,IL-1β)、前列腺素E2合成酶(prostaglandinE2synthase,PGES)以及单核细胞趋化蛋白-1(monocytechemotacticprotein-1,MCP-1)mRNA及蛋白表达水平。结果:IL-1RⅡ重组质粒导入后次日表达量最高,且升高持续实验整个过程至第17d。IL-1RⅡ治疗组的大鼠心/体重比值、心肌炎面积率、BNP及IL-1表达均较对照组有明显下降,大鼠左室心功能亦有明显改善。结论:应用流体动力学方法进行重组质粒IL-1RⅡ的体内导入治疗,对大鼠实验性自身免疫性心肌炎有改善左室功能和阻止心肌损害作用。     

TNF-α和cTnI在BALB/c小鼠自身免疫性心肌炎模型的动态变化

目的:以包含心肌球蛋白致病性抗原表位的人工合成多肽免疫BALB/c小鼠,建立实验性自身免疫性心肌炎动物模型,观察其自身免疫阶段和慢性病变期的病理变化,检测炎性因子和自身抗体变化.方法:人工合成含心肌肌球蛋白抗原重链表位长度为30个氨基酸残基的多肽0.8mg,纯化多肽皮下免疫遗传易感BALB/c小鼠,建立自身免疫性心肌炎模型,检测TNF-α和cTnI病变期间的改变.结果:实验组小鼠出现自身免疫性心肌炎病理改变.第14d出现心肌损伤,至第21d～30d心肌损伤达高峰,60d趋向稳定.心脏扩大,病理切片可见心肌层充血,间质巨噬细胞浸润明显,心肌细胞肿胀、逐步崩解坏死,被纤维组织取代.血清出现抗心肌肌球蛋白自身抗体阳性,并伴TNF-α和cTnI水平升高、高峰、下降的变化.结论:可成功诱导BALB/c系小鼠发病,建立实验性自身免疫性心肌炎动物模型,TNF-α和cTnI水平反映自身免疫性心肌炎病情发生、发展和转归.     

IL-21及其在自身免疫病中的研究进展

白介素-21(IL-21)是近年来被发现和关注的一个四螺旋束的细胞因子,主要由活化的CD4~+Th细胞和NKT细胞分泌,与IL-2、IL-4和IL-15具有高度同源性。它的受体属于Ⅰ型细胞因子受体,由α链和γc链组成,广泛分布于T细胞、B细胞、自然杀伤细胞、树突状细胞、巨噬细胞和角质化细胞等细胞表面,在固有免疫和适应性免疫中发挥重要作用。IL-21具有多效性,在类风湿性关节炎、系统性红斑狼疮、炎症性肠病等一些自身免疫病的发病机制中起着重要的作用。本文就IL-21及其与自身免疫病的关系作一综述。     

IL-1RⅡ和IL-1RAcP重组质粒对大鼠自身免疫性心肌炎的作用及机制

目的:研究白细胞介素1 Ⅱ型受体(IL-1RⅡ)和白细胞介素1受体辅助蛋白(IL-1RAcP)重组质粒对大鼠实验性自身免疫性心肌炎(EAM)的作用及其机制。方法:构建体内导入用重组质粒pCAGGS-IL-1RⅡ和pCAGGSIL-1RAcP,并以pCAGGS-SP(signal peptide)作为对照质粒。将雄性Lewis大鼠分成4组:对照(control)组(未免疫未注射质粒的大鼠,n=5)、EAM+SP组(免疫的大鼠尾静脉注射对照质粒,n=9)、EAM+IL-1RⅡ组(免疫的大鼠尾静脉注射IL-1RⅡ质粒,n=8)和EAM+IL-1RⅡ+IL-1RAcP组(免疫的大鼠尾静脉注射IL-1RⅡ和IL-1RAcP质粒,n=7)。第0天免疫大鼠造模;第6天应用流体动力学方法尾静脉注射重组质粒;第17天处死大鼠进行疗效评估,评估指标包括组织病理学、心脏彩超检测、心脏重量/体重比值、心肌中心衰标志物心房钠尿肽(ANP)和脑钠尿肽(BNP)及炎症因子的表达。构建体外细胞转染用重组质粒pUC19-IL-1RⅡ-actin和pUC19-IL-1RAcP-tub,转染入Cos7细胞获得培养上清液,将...     

肌球蛋白诱导大鼠自身免疫性心肌炎不同时期心功能及心肌病理学变化

目的:观察心肌肌球蛋白诱导自身免疫性心肌炎不同时间实验大鼠心功能及心肌组织病理学动态变化。方法:以猪心肌肌球蛋白为致病性抗原,与完全弗氏佐剂等体积混合成乳浊液在实验第1天、8天、30天皮下注射免疫Lewis大鼠作为心肌炎组,以完全弗氏佐剂皮下注射大鼠作为对照组。HE染色和Masson染色观察两组大鼠初次免疫后第21天、30天、90天心肌病理变化,超声心动图检测两组大鼠初次免疫后第21天、30天、90天的射血分数(EF)、左室短轴缩短分数(FS)、左室舒张末内径(LVEDd)、左室收缩末内径(LV-EDs)及左心室后壁厚度(LVPW)等指标。结果:免疫后不同时间超声心动图检测提示心肌炎组大鼠心功能较对照组明显下降(EF:84.25±2.17%vs93.45±4.13%,P<0.05;FS:48.49±4.36%vs63.17±4.49%,P<0.05;LVEDd:3.66±0.35mmvs4.63±0.32mm,P<0.05)。免疫后第21天,HE染色见心肌炎组大鼠心肌细胞肿胀、变性、坏死及不同程度的急性炎性细胞浸润,至第90天心肌组织炎症减弱,间质出现纤维化,胶原容积分数升高,对照组大鼠未出现心肌炎症及纤维化。结论:心肌肌球蛋白可诱导大鼠实验性自身免疫性心肌炎,急性期心功能受损主要由心肌炎症引起,慢性期病理学改变主要表现为心肌纤维化。     

实验性自身免疫性心肌炎小鼠模型研制

目的 :用BALB/c小鼠建立自身免疫性心肌炎动物模型。方法 :从新鲜猪心中分离提纯心肌肌凝蛋白。在第 1,第 8和第 3 0天用心肌肌凝蛋白和完全弗氏佐剂混合的乳浊液皮下注射免疫实验组小鼠 ,而在对照组仅用完全弗氏佐剂皮下注射。于初次免疫后的第14、第 2 1、第 3 0和第 60天收集血液和心脏标本 ,进行肌凝蛋白抗体和组织病理学检查。结果 :模型组第 14天到第 3 0天的标本中有不同程度的炎性反应和心肌细胞变性坏死 ,而 60天时出现了纤维化。同时在模型组小鼠血清中检测到肌凝蛋白抗体。结论 :通过免疫心肌肌凝蛋白发生自身免疫性心肌炎的BALB/c小鼠可作为良好的研究心肌炎和扩张型心肌病发病机制的动物模型     

HVEM过表达树突状细胞对自身免疫性心肌炎的作用

目的 探讨单纯疱疹病毒进入介导子(herpes virus entry mediator,HVEM)基因修饰的树突状细胞(dendritic cells,DC)能否防治肌凝蛋白诱导的小鼠心肌炎模型,并分析其机制.方法 以肌凝蛋白加弗氏佐剂免疫小鼠制备实验性自身免疫性心肌炎(EAM)动物模型,通过小鼠尾静脉输注肌凝蛋白冲击的HVEM基因修饰的DC,观察其对心肌炎的免疫保护作用,并探讨其可能机制.结果 HVEM基因修饰的DC能够抑制自身免疫应答造成的小鼠心肌损伤,其机制主要是通过分泌IL-10,并诱导产IL-10调节性T细胞(Tr1)抑制自身反应性T细胞的活化.结论 HVEM基因修饰的DC能抑制EAM的发生,并且HVEM介导的信号网络可能在不同的细胞中产生不同的作用.     

Regulation of IL-10 and IL-17 mediated experimental autoimmune encephalomyelitis by S-nitrosoglutathione

In this study, we investigated IL-10 and IL-17 specific immunomodulatory potential of S-nitrosoglutathione (GSNO), a physiological nitric oxide carrier molecule, in experimental autoimmune encephalomyelitis (EAE). In active EAE model, GSNO treatment attenuated EAE severity and splenic CD4⁺ T cells isolated from these mice exhibited decreased IL-17 expression without affecting the IFN-γ expression compared to the cells from untreated EAE mice. Similarly, adoptive transfer of these cells to nave mice resulted in reduction in IL-17 expression in the spinal cords of recipient mice with milder EAE severity. CD4⁺ T cells isolated from GSNO treated EAE mice, as compared to untreated EAE mice, still expressed lower levels of IL-17 under T_H17 skewing conditions, but expressed similar levels of IFN-γ under T_H1 skewing condition. Interestingly, under both T_H17 and T_H1 skewing condition, CD4⁺ T cells isolated from GSNO treated EAE mice, as compared to untreated EAE mice, expressed higher levels of IL-10 and adoptive transfer of these T_H17 and T_H1 skewed cells seemingly exhibited milder EAE disease. In addition, adoptive transfer of CD4⁺ T cells from GSNO treated EAE mice to active EAE mice also ameliorated EAE disease with induction of spinal cord expression of IL-10 and reduction in of IL-17, thus suggesting the participation of IL-10 mechanism in GSNO mediated immunomodulation. GSNO treatment of mice passively immunized with CD4⁺ T cells either from GSNO treated EAE mice or untreated mice further ameliorated EAE disease, supporting efficacy of GSNO for prophylaxis and therapy in EAE. Overall, these data document a modulatory role of GSNO in IL-17/IL-10 axis of EAE and other autoimmune diseases.     

腺病毒载体介导的共刺激分子融合蛋白对实验性自身免疫性心肌炎的作用

目的探讨腺病毒载体介导的共刺激分子融合蛋白CTLA4Ig与ICOSIg联合治疗对实验性自身免疫性心肌炎（EAM）的作用.方法猪心肌肌球蛋白免疫Lewis大鼠制成EAM模型.分别构建CTLA-4胞外域、ICOS胞外域与人IgG Fc段融合的腺病毒表达载体,常规方法生产表达上述融合蛋白的腺病毒用于治疗,免疫第14天注射后观察至第28天.第28天超声心动图检测心脏功能,苏木素-伊红（HE）染色观察心肌炎症程度,Western blot检测心肌CTLA-4、ICOS、ICOSL及B7-1、B7-2蛋白表达水平,ELISA检测血浆IL-2、IL-4和IFN-γ水平.结果CTLA4Ig、ICOSIg单独或联合治疗均使大鼠心功能指标、心肌炎症程度明显改善.Western blot显示联合治疗组CTLA-4、ICOSL及ICOS、B7-1蛋白表达下调,而B7-2表达差异无统计学意义.细胞因子平衡向TH2方向偏离.结论CTLA4Ig及ICOSIg联合阻断共刺激分子通路减轻EAM自身免疫性心肌损伤,改善大鼠心脏功能.其机制可能通过下调心肌组织CTLA-4、ICOS、ICOSL及B7-1蛋白表达.     

Absence of nonhematopoietic MHC class II expression protects mice from experimental autoimmune myocarditis

Experimental autoimmune myocarditis (EAM) is a CD4⁺ T‐cell‐mediated model of human inflammatory dilated cardiomyopathies. Heart‐specific CD4⁺ T‐cell activation is dependent on autoantigens presented by MHC class II (MHCII) molecules expressed on professional APCs. In this study, we addressed the role of inflammation‐induced MHCII expression by cardiac nonhematopoietic cells on EAM development. EAM was induced in susceptible mice lacking inducible expression of MHCII molecules on all nonhematopoietic cells (pIV?/? K14 class II transactivator (CIITA) transgenic (Tg) mice) by immunization with α‐myosin heavy chain peptide in CFA. Lack of inducible nonhematopoietic MHCII expression in pIV?/? K14 CIITA Tg mice conferred EAM resistance. In contrast, cardiac pathology was induced in WT and heterozygous mice, and correlated with elevated cardiac endothelial MHCII expression. Control mice with myocarditis displayed an increase in infiltrating CD4⁺ T cells and in expression of IFN‐γ, which is the major driver of nonhematopoietic MHCII expression. Mechanistically, IFN‐γ neutralization in WT mice shortly before disease onset resulted in reduced cardiac MHCII expression and pathology. These findings reveal a previously overlooked contribution of IFN‐γ to induce endothelial MHCII expression in the heart and to progress cardiac pathology during myocarditis.     

Immunohistochemical characterization of infiltrating mononuclear cells in the rat heart with experimental autoimmune giant cell myocarditis.

The pathogenesis of giant cell myocarditis remains unclear. Subsets of inflammatory infiltrating cells may reflect the pathogenesis and etiology of the disease. Therefore, we examined subsets of infiltrating mononuclear cells in the heart of the rat with experimental giant cell myocarditis. Lewis rats were immunized with cardiac myosin in Freund's complete adjuvant (FCA). Severe myocarditis characterized by congestive heart failure and multinucleated giant cells were elicited. The lesions were composed of predominant mononuclear cells, polymorphonuclear neutrophils and fragments of degenerated myocardial fibres. The subsets of infiltrating mononuclear cells were investigated using MoAbs against rat CD4+ T cell (W3/25), CD8+ T cell (CX8), B cell (OX33) and macrophage (OX42). By serial examination, bound immunoglobulin could only be found on degenerated myocardial fibres. In this model, most infiltrating mononuclear cells were composed of macrophages and CD4+ T cells. The frequencies of macrophages and CD4+ T cells were 73.7% and 13.8%, respectively. CD8+ T cells were scarce and B cells were rare in the lesions. The frequencies of CD8+ T cells and B cells were 4.5% and 0.4%, respectively. The dominance of macrophages and CD4+ T cells was the constant finding among the sites of the lesions and throughout the course of the disease. These characteristic subsets of infiltrating cells were in contrast to those of murine viral myocarditis which were mainly composed of natural killer (NK) cells and CD8+ T cells. Clarifying the subsets of infiltrating cells in myocarditis may contribute to differential diagnosis of myocarditis between viral and autoimmune types. From this study, the pathogenesis of experimental autoimmune giant cell myocarditis seemed to be closely related to CD4+ T cells and macrophages.     

Increased expression of caveolin-1 and -2 in the hearts of Lewis rats with experimental autoimmune myocarditis

The expression of caveolin-1, -2 and -3 was studied in the hearts of rats with experimental autoimmune myocarditis (EAM), to elucidate the involvement of caveolins in the pathogenesis of EAM. Western blot analysis showed that levels of caveolin-1 and -2 were significantly increased in the hearts of rats with EAM on day 14 post-immunization (pi), as compared to the hearts of normal controls (p < 0.05, normal controls vs. EAM). Caveolin-3 is already at a high level in control animals, so it does not increase further.

Immunohistochemistry showed that caveolin-1 was expressed mainly in ED1-positive macrophages and in some cardiomyocytes and vessels in the EAM lesions. Caveolin-2 was expressed constitutively in the vascular endothelial cells of normal hearts, and its expression was enhanced in EAM rats, as compared with the normal control group. Caveolin-3 was expressed constitutively in the plasma membranes of cardiomyocytes, but not in the vascular endothelial cells and inflammatory cells in the EAM lesions. Our results suggest that the expression of caveolin-1 and -2 is increased in EAM lesions and that the increased expression of caveolin-1 stimulates second signals in affected cells, such as macrophages and some cardiomyocytes, in EAM rats.     

Polarity of helper T cell subsets represents disease nature and clinical course of experimental autoimmune myocarditis in rats

The mechanisms of progression, remission and relapse of myocarditis remain unclear. To clarify these mechanisms, we focused on T helper-1 (Th1)/T helper-2 (Th2) subsets balance of peripheral lymphocytes and serum cytokine levels during disease progression in rats with experimental autoimmune myocarditis (EAM). Lewis rats were immunized with cardiac myosin on day 0. Blood samples were collected on days 0, 7, 15, 18, 21, 28, 35, 42, 49 and 56 following immunization. We examined percentages of interferon (IFN)-gamma and/or interleukin (IL)-4 producing cells in stimulated peripheral CD4-positive lymphocytes using flow cytometry analysis. Serum IFN-gamma, IL-2, IL-6 and IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA). The percentage of Th1/Th2 subsets in EAM on days 0, 15, 28 and 56 were 2.5 +/- 0.5/0.5 +/- 0.1%, 19.4 +/- 3.2/1.6 +/- 0.3%, 2.0 +/- 0.5/22.1 +/- 5.7% and 3.0 +/- 0.4/1.7 +/- 0.3%, respectively. Serum levels of Th1 cytokines, IFN-gamma and IL-2 significantly increased in the acute phase (from day 15-18) and immediately decreased in the early recovery phase. On the other hand, serum levels of Th2 cytokine, IL-10 significantly increased in the early recovery phase (from day 24-30). These results suggest that induction of acute myocarditis might be associated with systemic Th1 dominance, while recovery is related to systemic Th2 polarity. Thus, analysis of Th1/Th2 balance in peripheral T cells may be useful in disease monitoring in patients with myocarditis and postmyocarditic dilated cardiomyopathy.     

Alterations in creatine metabolism observed in experimental autoimmune myocarditis using ex vivo proton magic angle spinning MRS

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.