Establishment and effect evaluation of a stress cardiomyopathy mouse model induced by different doses of isoprenaline

Abstract

The optimum dose of isoprenaline (ISO) required to induce stress cardiomyopathy (SC) in mice is not known. The present study aimed to investigate the dose-response association and determine the optimum dose of ISO to establish a high-morbidity/low-mortality SC mouse model to simulate the clinical symptoms of SC. A total of 72 6-week-old wild-type female mice (C57BL/6) were randomly divided into control mice administered normal saline and mice treated with increasing ISO concentrations (5, 10, 25, 50 and 100 mg/kg ISO intraperitoneal injections daily for 14 consecutive days). All mice were analysed by body weight assessment, open field test (OFT), echocardiography (Echo), electrocardiogram (ECG), assessment of myocardial pathology and quantification of cortisol, brain natriuretic peptide (BNP), cardiac troponin T (cTnT), catecholamine (CA) and C-reactive protein (CRP). Compared with the control group, the 25 and 50 mg/kg ISO groups exhibited the most prominent weight changes and lower mortality. The open-field test showed a significant decrease in autonomous activity behaviour in the 25 and 50 mg/kg ISO groups compared with the control group (P<0.05). Echo revealed that the apex of the heart was balloon-like in the 25 and 50 mg/kg ISO groups, along with prominent left ventricular dyskinesia. ECG showed a significant increase in ST segment amplitude, QT interval and Q amplitude (P<0.05) in the 25 and 50 mg/kg ISO group compared with the control group. Haematoxylin and eosin staining of heart tissue showed a disordered arrangement of myocardial cells, dissolution of myocardial fibres and cytoplasm, notable widening of myocardial cell space, oedema and hyperaemia of the interstitium, whereas heart tissue of the control group was structurally intact. Compared with the control group, the 25 and 50 mg/kg ISO groups exhibited significantly higher levels of cortisol, BNP, cTNT, CA and CRP (P<0.05). A high-incidence low-mortality SC model was successfully and stably developed by administration of 25 and 50 mg/kg ISO. Such models may provide a basis for the development of other animal models of SC.

Animal models of Takotsubo syndrome: bridging the gap to the human condition

“…However, for the study to be clinically applicable, it is crucial that global cardiac function, when used as an outcome measure, be evaluated in the context of a TS phenotype. The impact of stress inducing a reduced global systolic function, in the absence of RWMA, appears to be a recurring finding observed by us and others ( 8 , 10 , 72 ). Thus, regions with wall motion abnormalities can be associated with segments displaying hyperkinesia, no change, or even hypokinesia.…”

“…• Mouse (16,72,(77)(78)(79)(80)(81)(82)(83)(84)(85) • Rat (11-15, 23, 86-103) • Monkey (9) • Gene-modified mouse (104) • Subarachnoid haemorrhage in rabbit (105) High dose of PDE-3 inhibitor in rat (106) Low-moderate dose of catecholamine in:…”

Exosomal miRNA‐21‐5p and miRNA‐21‐3p as key biomarkers of myocardial infarction

“…ISO is a catecholamine and causes severe myocardial necrosis. 29 , 30 The results showed in Figure 4 an increase in CK‐MB and troponin I after ISO‐induced stroke in the MI group compared with the control group. The mean serum CK‐MB activity in the control and MI groups was 86 ± 1 and 222 ± 8 IU/L, respectively, indicating a significant difference ( p < 0.0001).…”

“…ISO is a catecholamine and causes severe myocardial necrosis 29,30 . The results showed in Figure 4 an increase in CK‐MB and troponin I after ISO‐induced stroke in the MI group compared with the control group.…”

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia

“…In the published literature, epinephrine and isoproterenol have most commonly been used to create stress-induced cardiomyopathies in animal models, we chose epinephrine because it is also used clinically to treat septic shock. [10][11][12][13] Finally, although human and animal sepsis studies have shown that large vessel coronary perfusion is not impaired during sepsis, the cardiac microcirculation has not been evaluated for impaired tissue perfusion as a cause of cardiac injury. 14,15 We previously found in our large animal model of sepsis-induced cardiac dysfunction that the coronary microcirculation is damaged, but this finding was confounded by the use of exogenous catecholamines.…”