Department of Cardiology, Medical University of Warsaw, Poland.
Department of Experimental and Clinical Physiology, Laboratory of Center for Pr eclinical Research, Medical University of Warsaw, Poland.
Cardiol J. 2022;29(1):105-114. doi: 10.5603/CJ.a2020.0057. Epub 2020 Apr 24.
Takotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological characteristics in TTS.
Forty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining.
The total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24, 48, 72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084).
The ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient.
Takotsubo 综合征（TTS）是一种应激诱导的疾病，主要影响绝经后妇女。本研究旨在评估异丙肾上腺素（ISO）依赖性雌性大鼠模型和 TTS 的组织病理学特征。
49 只 12 周龄的 Sprague Dawley 雌性大鼠，腹腔内单次注射 ISO 剂量为 50（n = 8）、75（n = 6）、100（n = 3）、150（n = 27）和 200（n = 5）mg/kg 体重。对照组（n = 6）注射生理盐水。超声心动图检查评估壁运动异常，于 ISO 后 24、48、72 h 和 7 天进行。根据苏木精-伊红染色进行组织病理学分析。
总死亡率为 3/49（6.12%）。诱导 TTS 的最佳 ISO 剂量为 150mg/kg bw，27 只大鼠中有 21 只（77.77%）出现心尖球囊样改变。组织病理学分析显示心肌细胞局灶性坏死/凋亡，伴有炎症和成纤维细胞样细胞浸润。在 ISO 后 24、48、72 h，中心肌层的病灶数量最多，呈心尖-基底梯度（p < 0.05）。ISO 后 48 h，心尖与基底节段中心层（p = 0.0032）、心内膜心尖与基底节段（0.00024）和中腔与基底节段（p = 0.0483）的差异有统计学意义。ISO 后 48 h，150mg/kg bw 组和 200mg/kg bw 组大鼠心尖区心内膜病灶数量存在差异（p = 0.0084）。
与雄性 TTS 模型相比，ISO 雌性大鼠 TTS 模型具有更高的最佳剂量和更低的死亡率。TTS 表现为单一的心肌细胞疾病，病灶主要位于中心肌层，呈心尖-基底梯度。
