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.