Lymphokine activated killer cells in murine coxsackievirus B3 myocarditis

The purpose of the present study was to determine whether lymphokine activated killer (LAK) cells were involved in the development of coxsackievirus B3 (CB3) myocarditis in both the acute viremic (Experiment I) and the subacute aviremic (Experiment II) stages. To induce LAK cells, recombinant human interleukin-2 (IL-2) was administered to CB3-infected mice subcutaneously daily, starting on day 0 in Experiment I and on day 7 in Experiment II for 7 days, respectively. The treated groups were compared to infected controls. Splenic lymphocytes of IL-2 treated mice were further cultured in vitro in IL-2 containing medium for 7 days, and LAK cell activity, i.e., cytotoxic activity of the lymphocytes against EL-4 tumor cells and against cultured fetal myocytes, was assayed by⁵¹Cr-release method. In Experiment I, histologic scores, myocardial virus titers, and LAK cell activity did not differ significantly between IL-2 treated and untreated groups. In contrast, in Experiment II, there were more cellular infiltration associated with severe necrosis and higher LAK cell activity against EL-4 cells and cultured myocytes in IL-2 treated than in untreated groups. The presence of LAK cells was demonstrated in the subacute stage of murine CB3 myocarditis. Thus, the behavior of LAK cell activity may vary with the course of myocarditis, and enhanced LAK cell activity may be involved in the development of the disease.This work was supported by research grants from the Conference on Coronary Artery Disease, Japanese Education of Science and Walfare (Nos. 08877110 and 09470164), Kanae Shinyaku Foundation, and Japan Cardiovascular Research Foundation.     

急性心肌梗塞错误溶栓治疗12例分析

自1993年12月至1995年8月，对155例急性心肌梗塞（AMI）病人进行溶栓治疗，12例发生误溶(7．7％）。其中早期复极综合征4例，室壁瘤2例，心肌炎1例，心肌病1例，完全性左束支阻滞1例，间歇性左前分支阻滞互例，其它2例。本文分析了误溶病例与AMI的鉴别要点，并提出了减少误溶，提高诊疗水平的措施。     

Behçet's disease and cardiac arrhythmia

Summary Only few cases of cardiac conduction disturbances and arrhythmias have been reported in Behçet's disease. We recently observed the case of a 16-year-old woman with Behçet's disease in whom cardiac arrhythmia became the main clinical symptom. This observation and a review of the literature led us to the conclusion that arrhythmia could represent the clinical manifestation of an underlying myocarditis due to Behçet's disease and can be regarded as a feature of cardiac involvement of the disease.     

Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside

Genetic defects of the dystrophin-glycoprotein complex (DGC) cause hereditary dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have previously described a mechanism involved in enterovirus-induced dilated cardiomyopathy: The enteroviral protease 2A directly cleaves dystrophin in the hinge 3 region, leading to functional dystrophin impairment. During infection of mice with coxsackievirus B3, the DGC in the heart is disrupted and the sarcolemmal integrity is lost in virus-infected cardiomyocytes. Additionally, dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy in vivo, suggesting a pathogenetic role of the dystrophin cleavage in enterovirus-induced cardiomyopathy. Here, we extend these experimental findings to a patient with dilated cardiomyopathy due to a coxsackievirus B2 myocarditis. Endomyocardial biopsy specimens showed an inflammatory infiltrate and myocytolysis. Immunostaining for the enteroviral capsid antigen VP1 revealed virus-infected cardiomyocytes. Focal areas of cardiomyocytes displayed a loss of the sarcolemmal staining pattern for dystrophin and -sarcoglycan identical to previous findings in virus-infected mouse hearts. In vitro, coxsackievirus B2 protease 2A cleaved human dystrophin. These findings demonstrate that in human coxsackievirus B myocarditis a focal disruption of the DGC can principally occur and may contribute to the pathogenesis of human enterovirus-induced dilated cardiomyopathy.     

阿托伐他汀对Lewis大鼠实验性自身免疫性心肌炎作用的研究

目的： 探讨阿托伐他汀对实验性自身免疫性心肌炎(EAM）大鼠Th1/Th2偏离的影响及对EAM的治疗价值。方法: 6-8周雄性Lewis大鼠31只，其中8只作为正常对照；23只以猪心肌肌球蛋白免疫制成EAM模型，免疫后随机分为阿托伐他汀大剂量（10 mg·kg^-1·d^-1）组、小剂量（1 mg·kg^-1·d^-1）组和未治疗组，连续用药 21 d。第 21 d，行超声心动图检测；取心肌组织，观察大体及镜下炎症程度；ELISA检测血浆IL-2、IL-4、IL-10及IFN-γ等细胞因子水平,并以IFN-γ/IL-4比值作为Th1/Th2偏离方向指标。结果: 阿托伐他汀使EAM大鼠心室肥厚减轻，LVEDd降低，射血分数增加；心脏重量/体重比值及炎症程度分级显著降低；Th1型细胞因子(IFN-γ, IL-2)水平降低，Th2型细胞因子水平(IL-4, IL-10)升高。3组间TC、TG及HDL-C水平未见明显差异。结论: 阿托伐他汀使Th1/Th2平衡向Th1方向偏离，抑制EAM炎症反应。表明阿托伐他汀的免疫调节效应及在自身免疫病治疗中的应用前景。     

Spatiotemporal changes of coxsackievirus and adenovirus receptor in rat hearts during postnatal development and in cultured cardiomyocytes of neonatal rat

Coxsackievirus B is the most common cause of viral myocarditis and is particularly virulent in neonates and children. Adenovirus is also a leading cause of the disease. The determinant of tropism for both viruses is considered to be the expression of coxsackievirus and adenovirus receptor (CAR) in target organs. However, developmental change and physiological localization of CAR in the heart are unknown. We examined expression levels of CAR in rat hearts by quantitative real-time polymerase chain reaction and Western blot analysis and found that CAR decreased gradually during postnatal development, although CAR was detectable, even in adults. Immunohistochemistry revealed CAR on the whole surface of cardiomyocytes in immature rat hearts. In contrast, CAR was detected predominantly on intercalated disks in the adult heart and was accumulated especially at the contact point between the cultured cardiomyocytes, even though they were prepared from the neonatal rat heart. In conclusion, CAR was expressed abundantly on the whole surface of cardiomyocytes in immature rat hearts. Both the expression level and the localization of CAR are possible determinants of the susceptibility to viral myocarditis of neonates and children.     

中药心康口服液抗柯萨奇B3病毒RNA复制作用的研究

目的研究探讨中药心康口服液对感染心肌中柯萨奇B3病毒RNA复制的影响。方法小鼠感染柯萨奇病毒B3(CVB3)诱发急性病毒性心肌炎,于急性期治疗后提取鼠心肌总RNA,用逆转录-聚合酶链反应技术检测心肌CVB3RNA含量,经琼脂糖凝胶电泳后,在凝胶成像系统下观察。结果中药心康口服液能明显降低心肌CVB3-RNA的含量,与病毒对照组比较差异有统计学意义,P<0.01;感染期不同阶段心肌病毒RNA含量的检测显示,心康口服液2个治疗组的病毒含量的检出,并没有随着用药时间的延长而显著降低。结论中药心康口服液能有效地影响心肌CVB3RNA的复制,其对病毒的作用是抑制复制而非杀灭。     

心肌炎患者高频心电图QRS波群的功率谱分析

本文选取６９名心肌炎患者，９４名正常人做为对照。依其年龄不同，共分６组：幼儿心肌炎组，正常幼儿组，学龄心肌炎组，正常学龄组，成人心肌炎组，正常成人组。分别对这６组的Ⅱ导、ａＶＦ导、Ｖ２导、Ｖ５导ＱＲＳ波群０－１０００Ｈｚ、８０－３００Ｈｚ、１００－１０００Ｈｚ３个频段的功率谱（用绝对能量表示）进行了分析。结果提示，不同年龄的心肌炎患者，其心电信号高频频段的能量变化规律不一致。     

病毒性心肌炎小鼠心肌组织中趋化因子表达谱的改变及其意义

目的：研究病毒性心肌炎（VMC）小鼠心肌组织趋化因子（ChKs)表达谱变化，探讨ChKs在VMC发病中的可能作用及意义。方法：B3型柯萨奇病毒（CVB3）腹腔注射雄性BALB／c小鼠；RTPCR定性和定时定量分析心肌组织MCP－1、IP－10、Ltn和FKN等12种ChKs表达。病理切片和血清CKMB分析判定病变和病程程度。结果：（1）在所检测的12种ChKs中，VMC组呈阳性表达的有9种，显著多于正常组心肌组织的6种，有3种ChKs(BLC、Eot和LARC）两组均未检出；（2）VMC组9种阳性表达的ChKs中CVB3诱导性表达的为MIP－2、MIG和IP－10，6种组成性表达的ChKs在VMC时上调表达的有MIP－1β、MCP－1、MCP－2、Ltn等4种，下调表达的有RANTES，与正常对照组比未呈现明显差异的为FKN。（3）ChKs的表达消长存在一定的差异，感染4d后MIP－2等达高峰，随后下降；9d后出现MCP－1和RANTES表达上升峰；FKN在感染9d内表达较稳定。（4）亚急性早期、中期、中后期和晚期心肌组织ChKs表达谱有明显区别，各期ChKs表达谱中优势表达的ChKs分别为IP－10、IP－10、MCP－1、MCP－1。结论：VMC心肌组织ChKs呈成簇性方式改变，表达谱改变的复杂性可能与发病机制的复杂性有关，优势表达的ChKs可能在病毒性心肌炎发病中扮演着更重要的角色。