ECG detection of murine chagasic cardiomyopathy.
ECG detection of murine chagasic cardiomyopathy.
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DOI：
10.1645/ge-2396.1
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Hoft DF
中科院分区：
文献类型：
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作者：
Eickhoff CS;Lawrence CT;Sagartz JE;Bryant LA;Labovitz AJ;Gala SS;Hoft DF
由克氏锥虫引起的恰加斯病是感染性心肌炎的常见原因。最近的临床治疗试验和疫苗研究表明恰加斯免疫病理学是针对寄生虫而不是自身抗原。因此，疫苗可能具有预防疾病进展的潜力。小鼠和寄生虫菌株的某些组合产生显着的组织病理学，可用于新疫苗接种策略的安全性分析。本研究的目的是确定：（1）是否可以通过心电图来识别小鼠模型中恰加斯心肌病的发展； (2)这些潜在的恰加斯心电图变化是否与组织病理学发现相关。 BALB/c、C57BL/6 和 C3H 小鼠组感染不同的寄生虫菌株（Tulahuén、巴西或 Sylvio-X10/4），并每周通过心电图进行评估。定期从小鼠亚群中采集选定的组织用于盲法组织学评估。感染巴西和图拉胡恩品系寄生虫的 BALB/c 小鼠中，QT 间期延长的比例显着增加。在受感染的 BALB/c 小鼠中检测到的平均 QT 间期延长与恰加斯病组织病理学变化显着相关。这些结果表明，心电图可作为一种非侵入性方法来筛查导致小鼠模型中恰加斯心肌病的免疫介导损伤。恰加斯病是由寄生虫克氏锥虫感染引起的，是感染性心肌炎的最常见原因。全球有超过 1100 万人感染了这种原生寄生虫。目前，急性感染后尚无高效治疗方法，疫苗工作仍处于研究阶段。人类感染是在接种克氏锥虫寄生虫后开始的，通常是通过锥蝽昆虫（“接吻虫”）的粪便，通过对真皮的损伤或通过粘膜（例如眼睛）。尽管寄生虫血症严重，但感染急性期的特点是轻微的临床症状（发烧和不适）。患者通常会从这种急性疾病中康复，并进入感染的潜伏（或不确定）阶段，寄生虫持续性较低，可持续 10 至 40 年以上。据估计，30% 的感染者会发展为有症状的慢性感染阶段，其特征是心肌炎或巨结肠。最近的研究报告了慢性感染期间药物干预的进展，但在急性感染期间给予药物干预往往更能成功地减少疾病进展。然而，由于急性感染的检出率较低，因此通常不给予治疗。先前的研究表明，某些小鼠品系感染特定的寄生虫菌株可以引起骨骼肌和心脏组织的显着组织学变化。心电图研究是零星的，结果往往不令人信服。在我们目前的研究中，我们的目标是通过建立可以非侵入性测量的疾病模型，为未来的小鼠研究奠定基础。这不仅有助于更好地了解恰加斯病的自然进展，而且对于评估未来的疫苗接种策略也很有价值。
Chagas disease, induced by Trypanosoma cruzi, is a common cause of infectious myocarditis. Recent clinical treatment trials and vaccine studies indicate that chagasic immunopathology is directed against the parasite and not self-antigens. Therefore, vaccines may have the potential to protect against disease progression. Certain combinations of mouse and parasite strains produce significant histopathology and can be used for safety analyses of new vaccination strategies. The goals of this study were to determine: (1) if the development of Chagasic cardiomyopathy in the murine model could be identified by ECG; and (2) whether these potential Chagasic ECG changes would correlate with histopathologic findings. Groups of BALB/c, C57BL/6, and C3H mice were infected with different parasite strains (Tulahuén, Brazil or Sylvio-X10/4) and evaluated weekly by ECG. Selected tissues from subsets of mice were harvested periodically for blinded histologic evaluation. Significantly increased proportions of BALB/c mice infected with Brazil and Tulahuén strain parasites displayed prolonged QT intervals. Prolonged mean QT intervals detected in infected BALB/c mice significantly correlated with chagasic histopathologic changes. These results indicate that ECG can be used as a non-invasive method to screen for immune-mediated damage resulting in Chagasic cardiomyopathy in the murine model. Chagas disease, caused by infection with the parasite Trypanosoma cruzi, is the most common cause of infectious myocarditis. More than 11 million people are infected worldwide with this protozoan parasite. Currently, there are no highly effective treatments once an individual has proceeded past acute infection, and vaccine work is still in the research stage. Human infection begins after being inoculated with T. cruzi parasites, usually via the fecal matter of triatomine insects (`kissing bugs') through an insult to the dermis or via mucosal membranes, such as the eye. The acute phase of infection is characterized by mild clinical symptoms (fever and malaise) in spite of high parasitemia. Patients usually recover from this acute illness and enter the latent (or indeterminate) stage of the infection with low-level parasite persistence which can last from 10 to > 40 yr. An estimated 30% of infected individuals develop the symptomatic chronic stage of infection, which is characterized by myocarditis or megacolon. Recent studies report progress of drug intervention during chronic infection, but are more often successful in reducing progression towards disease when given during acute infection. However, with detection of acute infection being low, treatment is often not given. Previous studies have indicated that infection of certain mouse strains with specific parasite strains can induce significant histological changes in both skeletal muscle and cardiac tissue. ECG studies have been sporadic and results often unconvincing. In our current study, we aim to lay the groundwork for future murine investigation by establishing a disease model which can be measured non-invasively. This would not only be valuable in providing a better understanding of the natural progression of Chagas disease, but could also prove valuable in evaluation of future vaccination strategies.