病毒性心肌炎及其后遗症

临床证据提示，心肌受累可由病毒感染引起，组织病理学的心肌损害可能与大多数病毒感染有关，从人心脏重复地分离出来的病毒只有科萨奇，ＥＣＨＯ和脊髓灰白质炎等数种病毒，前两者已被确定为成人急性心肌炎的病因，并普遍以此解释病毒性心肌炎的大多数临床病例。本文选择性地讨论了成人病毒性心肌炎及其表现，阐述了病毒性心肌炎可能导致的晚期心脏后遗症的最新实验证据。     

Sex-Specific Effects of Plastic Caging in Murine Viral Myocarditis

Background: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. Methods: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. Results: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. Conclusions: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.     

Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-Proven Case Series

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14–39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty^® (Pfizer-BioNTech) (n = 11), Vaxzevria^® (AstraZenica) (n = 2) and Janssen^® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4⁺ and CD8⁺ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4⁺ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.     

SIAF对病毒性心肌炎模型鼠的治疗作用

目的 研究梅花鹿免疫细胞活性因子(SIAF)对病毒性心肌炎的治疗作用。方法 采用柯萨奇B3型病毒(CB_3 V)性心肌炎小鼠模型,检测心肌酶、心电图,观察心肌病理改变及死亡率。采用MTT法测定淋转及NK细胞毒活性。结果 SIAF能明显改善心肌损伤模型鼠的心电图及心肌病理损害;降低心肌酶含量;调节淋转及NK细胞毒活性。结论 SIAF对病毒性心肌炎具有一定治疗作用。     

Mechanism of Blood–Heart-Barrier Leakage: Implications for COVID-19 Induced Cardiovascular Injury

Although blood–heart-barrier (BHB) leakage is the hallmark of congestive (cardio-pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus variants such as the severe acute respiratory syndrome novel corona virus 2 (SARS-CoV-2) known as COVID-19, the mechanism is unclear. The goal of this project is to determine the mechanism of the BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from endocardium to the interstitium; however, this BHB is broken during CHF. Previous studies from our laboratory, and others have shown a robust activation of matrix metalloproteinase-9 (MMP-9) during CHF. MMP-9 degrades the connexins leading to EE dysfunction. We demonstrated juxtacrine coupling of EE with myocyte and mitochondria (Mito) but how it works still remains at large. To test whether activation of MMP-9 causes EE barrier dysfunction, we hypothesized that if that were the case then treatment with hydroxychloroquine (HCQ) could, in fact, inhibit MMP-9, and thus preserve the EE barrier/juxtacrine signaling, and synchronous endothelial-myocyte coupling. To determine this, CHF was created by aorta-vena cava fistula (AVF) employing the mouse as a model system. The sham, and AVF mice were treated with HCQ. Cardiac hypertrophy, tissue remodeling-induced mitochondrial-myocyte, and endothelial-myocyte contractions were measured. Microvascular leakage was measured using FITC-albumin conjugate. The cardiac function was measured by echocardiography (Echo). Results suggest that MMP-9 activation, endocardial endothelial leakage, endothelial-myocyte (E-M) uncoupling, dyssynchronous mitochondrial fusion-fission (Mfn2/Drp1 ratio), and mito-myocyte uncoupling in the AVF heart failure were found to be rampant; however, treatment with HCQ successfully mitigated some of the deleterious cardiac alterations during CHF. The findings have direct relevance to the gamut of cardiac manifestations, and the resultant phenotypes arising from the ongoing complications of COVID-19 in human subjects.     

中西医结合治疗病毒性心肌炎疗效观察

目的观察中西医结合治疗病毒性心肌炎的疗效。方法采用随机、双盲和1:1平行对照的试验方法。将40例患者随机分为治疗组和对照组,每组各20例。2组皆用西医常规治疗,其中治疗组在西医常规治疗的基础上加用中药(自拟抗毒益气汤),水煎服,每日1剂,15d为1个疗程。观察胸闷、胸痛、心悸、气促、倦怠乏力等临床症状症状的变化,心率及心电图改善情况。结果治疗组胸闷、胸痛、心悸、气促、乏力等临床症状和心率及心电图改善总有效率为90%(18/20例),对照组总有效率为70%(14/20例),2组治愈率与总有效率比较均有统计学意义(P<0.05)。结论中西医结合治疗病毒性心肌炎的临床疗效显著优于单纯西医治疗病毒性心肌炎的疗效。     

参麦注射液对急性病毒性心肌炎患者的血浆心钠素水平的影响

报道了分别应用参麦注射液(试验组)和GIK注射液(对照组)对40例急性病毒性心肌炎患者进行治疗,并做了治疗前后血浆心钠素(ANF)的动态测定。结果发现,随着治疗,血浆ANF上升。两组间相比,试验组患者血浆ANF上升较快。并对其机制进行了探讨。     

卡维地洛对柯萨奇病毒B3感染小鼠儿茶酚胺及IL-6表达水平的影响

目的: 研究卡维地洛对急性柯萨奇B3(CVB3)病毒性心肌炎小鼠的儿茶酚胺及炎症因子IL-6表达水平的影响。方法: 随机将80只雄性BALB/C小鼠分为3组:正常对照组(n=20),心肌炎组(n=30),卡维地洛组(n=30)。后两组经腹腔接种CVB3诱发急性病毒性心肌炎,感染 24 h 后卡维地洛组每日灌胃给予卡维地洛 10 mg/kg,连续 14 d。于接种第7和14天随机从各组抽取8只小鼠取血后处死并留取心脏等标本。比较干预组与对照组心肌病理改变,采用高效液相色谱-电化学法检测去甲肾上腺素含量,采用RT-PCR法检测心肌IL-6 mRNA的表达,采用酶联免疫吸附实验方法检测心肌IL-6蛋白的表达。结果: 与心肌炎组比较,卡维地洛组心肌病理损伤明显减轻。与正常组比较,病毒性心肌炎小鼠血浆去甲肾上腺素明显升高,卡维地洛干预后小鼠血浆去甲肾上腺素明显下降(P<0.05)。与正常组比较,心肌炎组心肌IL-6表达明显上调(P<0.05)。与心肌炎组比较,卡维地洛组IL-6表达明显下调(P<0.05)。结论: 卡维地洛通过抑制儿茶酚胺对心肌的毒性作用以及下调心肌IL-6表达水平,减轻心肌炎小鼠的心肌损害。