Strain Analysis in the Assessment of a Mouse Model of Cardiotoxicity due to Chemotherapy: Sample for Preclinical Research

Domenica Rea, Carmela Coppola, Antonio Barbieri, Maria Gaia Monti, Gabriella Misso, Giuseppe Palma, Sabrina Bimonte, Mayra Rachele Zarone, Antonio Luciano, Davide Liccardo, Piera Maiolino, Antonio Cittadini, Gennaro Ciliberto, Claudio Arra, Nicola Maurea

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)279-90
Number of pages12
JournalIn Vivo
Volume30
Issue number3
Publication statusPublished - 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

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