Key result
Isoprenaline induces Takotsubo syndrome with apical ballooning in ~78% of female rats.
Why the study?
Takotsubo syndrome is a stress-induced disorder affecting mostly postmenopausal women, prompting evaluation of an isoprenaline-dependent female rat model and its histopathological characteristics.
Does isoprenaline induce Takotsubo syndrome and specific histopathological changes in female rats?
Does isoprenaline induce Takotsubo syndrome and specific histopathological changes in female rats?
An isoprenaline dose of 150 mg/kg body weight effectively induces a Takotsubo syndrome model in female rats, characterized by apical ballooning and focal myocardial necrosis with an apical-basal gradient.
Establishes a female rat model of isoprenaline-induced Takotsubo syndrome; leaves open translation to human mechanisms or therapy.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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A 2020 study studied Takotsubo syndrome (n=55). Isoprenaline vs. Physiological saline was evaluated on Apical ballooning (Takotsubo syndrome induction) at 150 mg/kg bw dose. An isoprenaline dose of 150 mg/kg body weight induced Takotsubo syndrome with apical ballooning in 77.77% of female rats, presenting with focal cardiomyocyte necrosis and an apical-basal gradient.
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