Abstract
BACKGROUND: In recent years, the development of more effective anticancer drugs has provided great benefits in patients' quality of life by improving both prognosis and disease-free survival. Nevertheless, the frequency and severity of side-effects, with particular reference to cardiac toxicity, have gained particular attention. The purpose of this study was to create a precise and sensitive preclinical model, able to identify early contractile dysfunction in mice treated with chemotherapy, through use of speckle-tracking echocardiography.
MATERIALS AND METHODS: We generated a mouse model of cardiotoxicity induced by doxorubicin. C57BL 6 mice were divided into two groups, treated for 7 days by intraperitoneal injections of placebo (vehicle) or doxorubicin (2.17 mg/kg), in order to characterize the cardiac phenotype in vivo.
RESULTS: We demonstrated that doxorubicin caused ealy remodeling of the left ventricle: after two days of therapy, the radial, circumferential and strain rates were reduced respectively by 35%, 34%, and 39% (p-value ≤0.001). Moreover, histological analysis revealed that doxorubicin treatment increased fibrosis, cardiomyocyte diameter and apoptosis.
CONCLUSION: In a murine model of doxorubicin-induced cardiac injury, we detected left ventricular dysfunction followed by alterations in conventional echocardiographic indices. Our study suggests that a change in strain could be an effective early marker of myocardial dysfunction for new anticancer treatments and, in preclinical studies, it might also be a valuable indicator for the assessment of activity of cardioprotective agents.
Original language | English |
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Pages (from-to) | 279-90 |
Number of pages | 12 |
Journal | In Vivo |
Volume | 30 |
Issue number | 3 |
Publication status | Published - Apr 24 2016 |
Keywords
- Animals
- Antibiotics, Antineoplastic
- Apoptosis
- Biomechanical Phenomena
- Cardiomyopathies
- Cardiotoxicity
- Disease Models, Animal
- Doxorubicin
- Echocardiography
- Female
- Humans
- Mice, Inbred C57BL
- Myocardial Contraction
- Myocytes, Cardiac
- Time Factors
- Journal Article