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Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts

Agnieszka Kołodzińska, Katarzyna Czarzasta, Benedykt Szczepankiewicz, Monika Budnik, Renata Główczyńska, Anna Fojt, Tomasz Ilczuk, Krzysztof Krasuski, Sonia Borodzicz, Agnieszka Cudnoch-Jędrzejewska, Barbara Górnicka, Grzegorz Opolski
DOI: 10.5603/CJ.a2020.0057
·
Pubmed: 32329043

open access

Ahead of print
Original articles
Published online: 2020-04-17

Abstract

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.

Abstract

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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Keywords

Takotsubo syndrome, female rat model, stress-induced cardiomyopathy, reversible heart failure

About this article
Title

Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts

Journal

Cardiology Journal

Issue

Ahead of print

Article type

Original Article

Published online

2020-04-17

DOI

10.5603/CJ.a2020.0057

Pubmed

32329043

Keywords

Takotsubo syndrome
female rat model
stress-induced cardiomyopathy
reversible heart failure

Authors

Agnieszka Kołodzińska
Katarzyna Czarzasta
Benedykt Szczepankiewicz
Monika Budnik
Renata Główczyńska
Anna Fojt
Tomasz Ilczuk
Krzysztof Krasuski
Sonia Borodzicz
Agnieszka Cudnoch-Jędrzejewska
Barbara Górnicka
Grzegorz Opolski

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