Research Progress of Animal Models of Stress Cardiomyopathy

doi:10.12300/j.issn.1674-5817.2022.102

Abstract

Abstract:

Stress cardiomyopathy (SC) is an acute cardiomyopathy caused by intense mental stimulation or physical stress. Currently, few interventions are effective in reducing mortality, improving prognosis, or preventing recurrence in acute or chronic stages of SC. Therefore, it is particularly important to establish a reliable and effective SC animal model to study the pathogenesis and prevention of SC. In this paper, the preparation methods and evaluation indexes of SC models at home and abroad were reviewed, including the operation details of catecholamine hormone injection method, binding method, binding combined with electroshock method, binding combined with dehydration method, vagus nerve electrical stimulation and other modeling methods, as well as evaluation indexes such as open field test, cardiac ultrasound, electrocardiogram and ELISA, striving to provide useful reference for model selection and establishment of SC research.

Key words: Stress cardiomyopathy, Animal model, Modeling method, Evaluation index

CLC Number:

R-332

Haosheng WU,Hang SU,Chao ZHU,et al. Research Progress of Animal Models of Stress Cardiomyopathy[J]. Laboratory Animal and Comparative Medicine, 2023, 43(2): 173-179. DOI: 10.12300/j.issn.1674-5817.2022.102.

Figures/Tables 3

References 43

1	SHAH R M, SHAH M, SHAH S, et al. Takotsubo syndrome and COVID-19: associations and implications[J]. Curr Probl Cardiol, 2021, 46(3):100763. DOI:10.1016/j.cpcardiol.2020. 100763 .
2	BARBIERI L, GALLI F, CONCONI B, et al. Takotsubo syndrome in COVID-19 era: is psychological distress the key? [J]. J Psychosom Res, 2021, 140:110297. DOI:10.1016/j.jpsychores. 2020.110297 .
3	CASTILLO RIVERA A M, RUIZ-BAILÉN M, RUCABADO AGUILAR L. Takotsubo cardiomyopathy - a clinical review[J]. Med Sci Monit, 2011, 17(6): RA135-RA147. DOI:10.12659/msm. 881800 .
4	OKURA H. Update of takotsubo syndrome in the era of COVID-19[J]. J Cardiol, 2021, 77(4):361-369. DOI:10.1016/j.jjcc. 2020.10.004 .
5	CHHABRA L. Prognostication in takotsubo syndrome[J]. Rev Cardiovasc Med, 2022, 23(3):110. DOI:10.31083/j.rcm2303110 .
6	TEMPLIN C, GHADRI J R, DIEKMANN J, et al. Clinical features and outcomes of takotsubo (stress) cardiomyopathy[J]. N Engl J Med, 2015, 373(10):929-938. DOI:10.1056/NEJMoa1406761 .
7	LYON A R, CITRO R, SCHNEIDER B, et al. Pathophysiology of takotsubo syndrome[J]. J Am Coll Cardiol, 2021, 77(7):902-921. DOI:10.1016/j.jacc.2020.10.060 .
8	LI C M, HUANG D, TANG J, et al. ClC-3 chloride channel is involved in isoprenaline-induced cardiac hypertrophy[J]. Gene, 2018, 642:335-342. DOI:10.1016/j.gene.2017.11.045 .
9	张志红. 硫化氢对Takotsubo心肌病的保护作用及其机制探讨[D].石家庄: 河北医科大学, 2017.
	ZHANG Z H. Protective effect of H₂S on takotsubo cardiomyopathy and its mechanism[D]. Shijiazhuang: Hebei Medical University, 2017.
10	ALI A, REDFORS B, ALKHOURY J, et al. Sacubitril/valsartan decreases mortality in the rat model of the isoprenaline-induced takotsubo-like syndrome[J]. ESC Heart Fail, 2021, 8(5):4130-4138. DOI:10.1002/ehf2.13530 .
11	QI C L, SHAO Y Z, LIU X S, et al. The cardioprotective effects of icariin on the isoprenaline-induced takotsubo-like rat model: involvement of reactive oxygen species and the TLR4/NF-κB signaling pathway[J]. Int Immunopharmacol, 2019, 74:105733. DOI:10.1016/j.intimp.2019.105733 .
12	杜志君, 蔡伟文, 张文静, 等. 典型与非典型应激性心肌病大鼠模型的制备方法[J]. 广东医学, 2016, 37(7):953-957. DOI:10.13820/j.cnki.gdyx.2016.07.001 .
	DU Z J, CAI W W, ZHANG W J, et al. Research on the rat model establishment methods of typical and atypical stress cardiomyopathy[J]. Guangdong Med J, 2016, 37(7):953-957. DOI:10.13820/j.cnki.gdyx.2016.07.001 .
13	GODSMAN N, KOHLHAAS M, NICKEL A, et al. Metabolic alterations in a rat model of takotsubo syndrome[J]. Cardiovasc Res, 2021, 118(8):1932-1946. DOI:10.1093/cvr/cvab081 .
14	尹元立, 高永红. 血清缺血修饰白蛋白与大鼠应激性心肌病相关性分析[J]. 中国循证心血管医学杂志, 2018, 10(5):621-624. DOI:10.3969/j.issn.1674-4055.2018.05.30 .
	YIN Y L, GAO Y H. Correlation between serum ischemia modified albumin and rat Takotsubo cardiomyopathy[J]. Chin J Evid Based Cardiovasc Med, 2018, 10(5):621-624. DOI:10.3969/j.issn.1674-4055.2018.05.30 .
15	蔡伟文, 杜志君, 查道刚. 大鼠应激性心肌病模型及其复发模型的制备[J]. 岭南心血管病杂志, 2016, 22(3):315-319. DOI:10.3969/j.issn.1007-9688.2016.02.18 .
	CAI W W, DU Z J, ZHA D G. Preparation for rat model of stress-induced cardiomyopathy and its recurrence model[J]. South China J Cardiovasc Dis, 2016, 22(3):315-319. DOI:10.3969/j.issn.1007-9688.2016.02.18 .
16	LIAO X D, CHANG E, TANG X M, et al. Cardiac macrophages regulate isoproterenol-induced takotsubo-like cardiomyo-pathy[J]. JCI Insight, 2022, 7(3): e156236. DOI:10.1172/jci.insight.156236 .
17	SHAO Y Z, REDFORS B, STÅHLMAN M, et al. A mouse model reveals an important role for catecholamine-induced lipotoxicity in the pathogenesis of stress-induced cardiomyopathy[J]. Eur J Heart Fail, 2013, 15(1):9-22. DOI:10.1093/eurjhf/hfs161 .
18	向仕钊, 卞洲艳, 周恒, 等. 比索洛尔联合还原型谷胱甘肽改善应激性心肌病心肌重构[J]. 中国心血管杂志, 2015, 20(5):358-365. DOI:10.3969/j.issn.1007-5410.2015.05.011 .
	XIANG S Z, BIAN Z Y, ZHOU H, et al. Combined utilization of bisoprolol and glutathione attenuates ventricular remodeling of takotsubo cardiomyopathy in mice[J]. Chin J Cardiovasc Med, 2015, 20(5):358-365. DOI:10.3969/j.issn.1007-5410.2015.05.011 .
19	KHURANA I, MAXWELL S, ROYCE S, et al. SAHA attenuates Takotsubo-like myocardial injury by targeting an epigenetic Ac/Dc axis[J]. Signal Transduct Target Ther, 2021, 6:159. DOI:10.1038/s41392-021-00546-y .
20	WALSH-WILKINSON E, ARSENAULT M, COUET J. Segmental analysis by speckle-tracking echocardiography of the left ventricle response to isoproterenol in male and female mice[J]. PeerJ, 2021, 9: e11085. DOI:10.7717/peerj.11085 .
21	万坤铭, 孙帅, 俞超芹. 应激致功能性下丘脑性闭经动物模型研究进展[J]. 南昌大学学报(医学版), 2022, 62(1):99-104. DOI:10.13764/j.cnki.ncdm.2022.01.020 .
	WAN K M, SUN S, YU C Q. Advances in animal models of stress-induced functional hypothalamic amenorrhea[J]. J Nanchang Univ Med Sci, 2022, 62(1):99-104. DOI:10.13764/j.cnki.ncdm.2022.01.020 .
22	高源, 郭翠娟, 刘仁平, 等. 束缚应激对小鼠卵巢氧化损伤的实验研究[J]. 南昌大学学报(医学版), 2022, 62(2):26-30. DOI:10.13764/j.cnki.ncdm.2022.02.005 .
	GAO Y, GUO C J, LIU R P, et al. A study on ovarian oxidative damage caused by restraint stress in mice[J]. J Nanchang Univ Med Sci, 2022, 62(2):26-30. DOI:10.13764/j.cnki.ncdm.2022.02.005 .
23	齐跃, 房加雄, 董彦, 等. 束缚诱导大鼠应激性心肌病的有效性评价[J]. 武警后勤学院学报(医学版), 2016, 25(10):791-794. DOI:10.16548/j.2095-3720.2016.10.004 .
	QI Y, FANG J X, DONG Y, et al. Evaluation of the immobilization effectiveness on inducing stress cardiomyopathy in rats[J]. J Logist Univ PAP Med Sci, 2016, 25(10):791-794. DOI:10.16548/j.2095-3720.2016.10.004 .
24	李永丰, 吴宇蔚, 乔海法. 足底电击应激诱发精神疾病模型的研究进展[J]. 神经解剖学杂志, 2020, 36(4):464-468. DOI:10.16557/j.cnki.1000-7547.2020.04.018 .
	LI Y F, WU Y W, QIAO H F. Research progress of the mental illness model induced by plantar shock stress[J]. Chin J Neuroanat, 2020, 36(4):464-468. DOI:10.16557/j.cnki.1000-7547.2020.04.018 .
25	李凤, 李玉军, 王凯, 等. 大鼠应激性心肌病模型心肌组织BNP的表达变化[J]. 中国法医学杂志, 2015, 30(5):459-462, 467. DOI:10.13618/j.issn.1001-5728.2015.05.003 .
	LI F, LI Y J, WANG K, et al. Expression of BNP in a rat model of stress cardiomyopathy[J]. Chin J Forensic Med, 2015, 30(5):459-462, 467. DOI:10.13618/j.issn.1001-5728.2015.05.003 .
26	阿兰达. 大鼠应激性心肌病神经肽Y和PGC-1α表达的实验研究[D]. 武汉: 华中科技大学, 2010.
	ANANDA S. An Experimental study on the expression of Neuropeptide Y and PGC-1α in a rat model of Stress Cardiomyopathy[D]. Wuhan: Huazhong University of Science and Technology, 2010.
27	石建, 曾安宁, 熊德高. 灯盏花素改善应激性心肌病大鼠心功能异常的机制[J]. 中国老年学杂志, 2016, 36(15):3646-3648. DOI:10.3969/j.issn.1005-9202.2016.15.016 .
	SHI J, ZENG A N, XIONG D G. Mechanism of breviscapine in improving cardiac dysfunction in rats with stress cardiomyopathy[J]. Chin J Gerontol, 2016, 36(15):3646-3648. DOI:10.3969/j.issn.1005-9202.2016.15.016 .
28	孙艳荣, 富华颖. 制动联合脱水建立应激性心肌病大鼠模型[J]. 泰山医学院学报, 2017, 38(5):497-499. DOI:10. 3969 / j. issn. 1004-7115.2017.05.006 .
	SUN Y R, FU H Y. Establishment of rat model of stress induced cardiomyopathy by combination of braking and dehydration[J]. J Taishan Med Coll, 2017, 38(5):497-499. DOI:10. 3969 / j. issn. 1004-7115.2017.05.006 .
29	郭瑞威, 杨丽霞, 奚银艳, 等. 电刺激迷走神经建立应激性心肌病家兔模型[J]. 实验动物与比较医学, 2016, 36(3):186-189. DOI:10.3969/j.issn.1674-5817.2016.03.005 .
	GUO R W, YANG L X, XI Y Y, et al. Establishment of stress induced cardiomyopathy model by stimulation of vagus nerve with electricity signal in rabbit[J]. Lab Anim Comp Med, 2016, 36(3):186-189. DOI:10.3969/j.issn.1674-5817.2016.03.005 .
30	GOULD T D, DAO D T, KOVACSICS C E. The open field test[M]//Pietropaolo P. Mood and anxiety related phenotypes in mice. Totowa: Humana Press, 2009:1-20. DOI:10.1007/978-1-60761-303-9_1 .
31	THIPPESWAMY B S, MISHRA B, VEERAPUR V P, et al. Anxiolytic activity of Nymphaea alba Linn. in mice as experimental models of anxiety[J]. Indian J Pharmacol, 2011, 43(1):50-55. DOI:10.4103/0253-7613.75670 .
32	LIPKIND D, SAKOV A, KAFKAFI N, et al. New replicable anxiety-related measures of wall vs center behavior of mice in the open field[J]. J Appl Physiol (1985), 2004, 97(1):347-359. DOI:10.1152/japplphysiol.00148.2004 .
33	YAKUPOGLU H Y, SAEED S, SENIOR R, et al. Reversible exercise-induced left ventricular dysfunction in symptomatic patients with previous Takotsubo syndrome: insights from stress echocardiography[J]. Eur Heart J Cardiovasc Imaging, 2020:jeaa237. DOI:10.1093/ehjci/jeaa237 .
34	LEE M. Time course of functional recovery in takotsubo (stress) cardiomyopathy: a serial speckle tracking echocardiography and electrocardiography study[J]. J Cardiovasc Imaging, 2020, 28(1):50-60. DOI:10.4250/jcvi.2019. 0083 .
35	SEMELKA R C, TOMEI E, WAGNER S, et al. Interstudy reproducibility of dimensional and functional measurements between cine magnetic resonance studies in the morphologically abnormal left ventricle[J]. Am Heart J, 1990, 119(6):1367-1373. DOI:10.1016/S0002-8703(05)80187-5 .
36	MITSUMA W, KODAMA M, ITO M, et al. Serial electrocardiographic findings in women with takotsubo cardiomyopathy[J]. Am J Cardiol, 2007, 100(1):106-109. DOI:10.1016/j.amjcard.2007.02.062 .
37	ABRAHAM J, MUDD J O, KAPUR N, et al. Stress cardiomyopathy after intravenous administration of catecholamines and beta-receptor agonists[J]. J Am Coll Cardiol, 2009, 53(15):1320-1325. DOI:10.1016/j.jacc.2009.02.020 .
38	GIANNI M, DENTALI F, GRANDI A M, et al. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review[J]. Eur Heart J, 2006, 27(13):1523-1529. DOI:10.1093/eurheartj/ehl032 .
39	CHHABRA L, BUTT N, AHMAD S A, et al. Electro-cardiographic changes in takotsubo cardiomyopathy[J]. J Electrocardiol, 2021, 65:28-33. DOI:10.1016/j.jelectrocard. 2020.12.006 .
40	DJURIĆ I, OBRADOVIĆ S, GLIGIĆ B. Dynamics of electrocardiographic changes, brain-natriuretic peptide and cortisol levels in a patient with stress (takotsubo) cardiomyopathy: a case report[J]. Vojnosanit Pregl, 2013, 70(5):511-515. DOI:10.2298/vsp1305511d .
41	MADHAVAN M, BORLAUG B A, LERMAN A, et al. Stress hormone and circulating biomarker profile of apical ballooning syndrome (Takotsubo cardiomyopathy): insights into the clinical significance of B-type natriuretic peptide and troponin levels[J]. Heart, 2009, 95(17):1436-1441. DOI:10.1136/hrt.2009.170399 .
42	AHMED K A, MADHAVAN M, PRASAD A. Brain natriuretic peptide in apical ballooning syndrome (Takotsubo/stress cardiomyopathy): comparison with acute myocardial infarction[J]. Coron Artery Dis, 2012, 23(4):259-264. DOI:10.1097/MCA.0b013e3283526a57 .
43	JOHANSSON G, JONSSON L, LANNEK N, et al. Severe stress-cardiopathy in pigs[J]. Am Heart J, 1974, 87(4):451-457. DOI:10.1016/0002-8703(74)90170-7 .

动物 Animal	品种或品系 Stock or strain	性别 Sex	年龄或体质量 Age/weight	药物 Drug	剂量 Dose	给药方案 Dosage regimen	参考文献 Reference
大鼠 Rat	SD	雄	250～300 g	ISO	50 mg/kg	单次腹腔注射	[9]
	SD	雌	2～4月龄，241±55 g	ISO	100 mg/kg	单次腹腔注射	[13]
	SD	雄	220～250 g，8周龄	ISO	100 mg/kg	不同部位多点皮下注射，持续3周	[14]
	SD	雌	300～350 g	NE	2～4 mg/kg	单次腹腔注射	[12]
	SD	雌	300～350 g	NE	4 mg/kg	单次腹腔注射	[15]
小鼠Mice	C57BL/6J	雄/雌	8～16周龄	ISO	200 mg/kg	单次腹腔注射	[16]
	C57BL/6J	/	16周	ISO	400 mg/kg	单次腹腔注射	[17]
	C57BL/6J	雄性	7周龄，20～25 g	ISO	50 mg/kg	腹腔注射3周	[18]
	129/Sv	/	8周	ISO	25 mg/kg	连续皮下注射5 d	[19]
	C57BL/ 6J	雄/雌	8周	ISO	30 mg/kg	皮下埋置微渗透泵，连续21 d释放ISO	[20]

动物 Animal	品种或品系 Stock or strain	性别 Sex	年龄或体质量 Age/weight	药物 Drug	剂量 Dose	给药方案 Dosage regimen	参考文献 Reference
大鼠 Rat	SD	雄	250～300 g	ISO	50 mg/kg	单次腹腔注射	[9]
	SD	雌	2～4月龄，241±55 g	ISO	100 mg/kg	单次腹腔注射	[13]
	SD	雄	220～250 g，8周龄	ISO	100 mg/kg	不同部位多点皮下注射，持续3周	[14]
	SD	雌	300～350 g	NE	2～4 mg/kg	单次腹腔注射	[12]
	SD	雌	300～350 g	NE	4 mg/kg	单次腹腔注射	[15]
小鼠Mice	C57BL/6J	雄/雌	8～16周龄	ISO	200 mg/kg	单次腹腔注射	[16]
	C57BL/6J	/	16周	ISO	400 mg/kg	单次腹腔注射	[17]
	C57BL/6J	雄性	7周龄，20～25 g	ISO	50 mg/kg	腹腔注射3周	[18]
	129/Sv	/	8周	ISO	25 mg/kg	连续皮下注射5 d	[19]
	C57BL/ 6J	雄/雌	8周	ISO	30 mg/kg	皮下埋置微渗透泵，连续21 d释放ISO	[20]

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