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Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of non-reperfused myocardial infarction.
American Journal of Physiology-Heart and Circulatory Physiology ( IF 4.8 ) Pub Date : 2020-09-04 , DOI: 10.1152/ajpheart.00318.2020
Anis Hanna 1 , Arti V Shinde 1 , Nikolaos G Frangogiannis 1
Affiliation  

In patients with myocardial infarction (MI), cardiac rupture is an uncommon, but catastrophic complication. In the mouse model of non-reperfused MI, reported rupture rates are highly variable, and depend not only on the genetic background and sex of animals, but also on the method used for documentation of rupture. In most studies, diagnosis of cardiac rupture is based on visual inspection during autopsy; however, criteria are poorly defined. We performed systematic histopathologic analysis of whole hearts from C57BL6J mice dying after non-reperfused MI, and evaluated the reliability of autopsy-based criteria in identification of rupture. Moreover, we compared the cell biological environment of the infarct between rupture-related and rupture-independent deaths. Histopathological analysis documented rupture in 50% of mice dying during the first week post-MI. Identification of a gross rupture site was highly specific, but had low sensitivity; in contrast, hemothorax had high sensitivity, but low specificity. Mice with rupture had lower myofibroblast infiltration, accentuated macrophage influx, and a trend towards reduced collagen content in the infarct. Male mice had increased mortality and higher incidence of rupture. However, infarct myeloid cells harvested from male and female mice at the peak of the incidence of rupture had comparable inflammatory gene expression. In conclusion, the reliability of autopsy in documentation of rupture in infarcted mice is dependent on the specific criteria used. Macrophage-driven inflammation and reduced activation of collagen-secreting reparative myofibroblasts may be involved in the pathogenesis of post-MI cardiac rupture.

中文翻译:

在非再灌注心肌梗死小鼠模型中验证诊断标准和心脏破裂的组织病理学特征。

在心肌梗塞 (MI) 患者中,心脏破裂是一种罕见但灾难性的并发症。在非再灌注 MI 的小鼠模型中,报告的破裂率变化很大,不仅取决于动物的遗传背景和性别,还取决于用于记录破裂的方法。在大多数研究中,心脏破裂的诊断是基于尸检时的目视检查;然而,标准不明确。我们对非再灌注 MI 后死亡的 C57BL6J 小鼠的整个心脏进行了系统的组织病理学分析,并评估了基于尸检的标准在鉴定破裂方面的可靠性。此外,我们比较了与破裂相关的死亡和与破裂无关的死亡之间梗塞的细胞生物学环境。组织病理学分析记录了 50% 的小鼠在 MI 后第一周死亡的破裂。大体破裂部位的识别具有高度的特异性,但敏感性较低;相比之下,血胸的敏感性高,但特异性低。破裂小鼠的肌成纤维细胞浸润较低,巨噬细胞流入加剧,并且梗塞中胶原含量有减少的趋势。雄性小鼠死亡率增加,破裂发生率更高。然而,在破裂发生高峰期从雄性和雌性小鼠中采集的梗塞骨髓细胞具有相当的炎症基因表达。总之,尸检在梗塞小鼠破裂记录中的可靠性取决于所使用的具体标准。
更新日期:2020-09-07
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