open access
Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts
Affiliations- 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
- Department of Pathology, Medical University of Warsaw, Poland
- Department of Medical Informatics and Telemedicine, Medical University of Warsaw, Poland
- Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland
open access
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.
Keywords
Takotsubo syndrome, female rat model, stress-induced cardiomyopathy, reversible heart failure
About this articleTitle
Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts
Journal
Issue
Article type
Original Article
Pages
105-114
Published online
2020-04-17
Page views
6273
Article views/downloads
1484
DOI
Pubmed
Bibliographic record
Cardiol J 2022;29(1):105-114.
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
References (27)- Akashi YJ, Goldstein DS, Barbaro G, et al. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation. 2008; 118(25): 2754–2762.
- Hafiz AM, Jan MF, Paterick TE. Takotsubo Cardiomyopathy. 2012; 30: 683-708 in Cardiomyopathies – from basic research to clinical management. Edited by Prof. J. Veselka. Publisher InTech. Published 15.02.2012.
- Templin C, et al. Ghadri JR, Diekmann J Clinical features and outcomes of Takotsubo (stress) cardiomyopathy. N Engl J Med. 2015; 373: 929–38.
- Opolski G, Pawlak MM, Roik MF, et al. Clinical presentation, treatment, and long-term outcomes in patients with takotsubo cardiomyopathy. Experience of a single cardiology center. Pol Arch Med Wewn. 2010; 120(6): 231–236.
- Opolski G, Kochanowski J, Torbicki A, et al. The recurrence after ten years - "mother in-law variant" of tako-tsubo syndrome. Kardiol Pol. 2010; 68(5): 557–561.
- Opolski G, Budnik M, Kochanowski J, et al. Four episodes of takotsubo cardiomyopathy in one patient. Int J Cardiol. 2016; 203: 53–54.
- Budnik M, Piatkowski R, Kochanowski J, et al. The oldest patient with takotsubo cardiomyopathy. J Geriatr Cardiol. 2015; 12(5): 588–589.
- Lyon AR, Rees PSC, Prasad S, et al. Stress (Takotsubo) cardiomyopathy--a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med. 2008; 5(1): 22–29.
- Wright PT, Tranter MH, Morley-Smith AC, et al. Pathophysiology of takotsubo syndrome: temporal phases of cardiovascular responses to extreme stress. Circ J. 2014; 78(7): 1550–1558.
- Coupez E, Eschalier R, Pereira B, et al. A single pathophysiological pathway in Takotsubo cardiomyopathy: Catecholaminergic stress. Arch Cardiovasc Dis. 2014; 107(4): 245–252.
- Mori H, Ishikawa S, Kojima S, et al. Increased responsiveness of left ventricular apical myocardium to adrenergic stimuli. Cardiovasc Res. 1993; 27(2): 192–198.
- Uchida Y, Egami H, Uchida Y, et al. Possible participation of endothelial cell apoptosis of coronary microvessels in the genesis of Takotsubo cardiomyopathy. Clin Cardiol. 2010; 33(6): 371–377.
- Shao Y, Redfors B, Scharin Täng M, et al. Novel rat model reveals important roles of β-adrenoreceptors in stress-induced cardiomyopathy. Int J Cardiol. 2013; 168(3): 1943–1950.
- Young P. The Intensive Care Unit Drug Manual. Life in the Fast Lane. 2010.
- Watson LE, Sheth M, Denyer RF, et al. Baseline echocardiographic values for adult male rats. J Am Soc Echocardiogr. 2004; 17(2): 161–167.
- Weytjens C, Cosyns B, D'hooge J, et al. Doppler myocardial imaging in adult male rats: reference values and reproducibility of velocity and deformation parameters. Eur J Echocardiogr. 2006; 7(6): 411–417.
- Redfors B, Ali A, Shao Y, et al. Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner. Int J Cardiol. 2014; 174(2): 330–336.
- Iacucci I, Carbone I, Cannavale G, et al. Myocardial oedema as the sole marker of acute injury in Takotsubo cardiomyopathy: a cardiovascular magnetic resonance (CMR) study. Radiol Med. 2013; 118(8): 1309–1323.
- Elsokkari I, Cala A, Khan S, et al. Takotsubo cardiomyopathy: not always innocent or predictable. A unique post mortem insight. Int J Cardiol. 2013; 167(2): e46–e48.
- Sachdeva J, Dai W, Kloner RA. Functional and histological assessment of an experimental model of Takotsubo's cardiomyopathy. J Am Heart Assoc. 2014; 3(3): e000921.
- Kołodzińska A, Czarzasta K, Szczepankiewicz B, et al. Toll-like receptor expression and apoptosis morphological patterns in female rat hearts with takotsubo syndrome induced by isoprenaline. Life Sci. 2018; 199: 112–121.
- Frey N, Katus HA, Olson EN, et al. Hypertrophy of the heart: a new therapeutic target? Circulation. 2004; 109(13): 1580–1589.
- Timmers L, Sluijter JPG, van Keulen JK, et al. Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. Circ Res. 2008; 102(2): 257–264.
- Ueyama T, Kasamatsu K, Hano T, et al. Catecholamines and estrogen are involved in the pathogenesis of emotional stress-induced acute heart attack. Ann N Y Acad Sci. 2008; 1148: 479–485.
- Ueyama T, Hano T, Kasamatsu K, et al. Estrogen attenuates the emotional stress-induced cardiac responses in the animal model of Tako-tsubo (Ampulla) cardiomyopathy. J Cardiovasc Pharmacol. 2003; 42 Suppl 1: S117–S119.
- Thawornkaiwong A, Preawnim S, Wattanapermpool J. Upregulation of beta 1-adrenergic receptors in ovariectomized rat hearts. Life Sci. 2003; 72(16): 1813–1824.
- Kuo BT, Choubey R, Novaro GM. Reduced estrogen in menopause may predispose women to takotsubo cardiomyopathy. Gend Med. 2010; 7(1): 71–77.
