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



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.



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.



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.
Animal Facility Unit, Department of Experimental Oncology, "G. Pascale Foundation", IRCCS, Naples, Italy d.rea@istitutotumori.na.it.
Domenica
D
Rea
Cardiology Unit, "G. Pascale Foundation", IRCCS, Naples, Italy.
Carmela
C
Coppola
Animal Facility Unit, Department of Experimental Oncology, "G. Pascale Foundation", IRCCS, Naples, Italy d.rea@istitutotumori.na.it.
Antonio
A
Barbieri
Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Maria Gaia
MG
Monti
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Gabriella
G
Misso
Animal Facility Unit, Department of Experimental Oncology, "G. Pascale Foundation", IRCCS, Naples, Italy d.rea@istitutotumori.na.it.
Giuseppe
G
Palma
Division of Abdominal Surgical Oncology, Hepatobiliary Unit, "G. Pascale Foundation", IRCCS, Naples, Italy.
Sabrina
S
Bimonte
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Mayra Rachele
MR
Zarone
Animal Facility Unit, Department of Experimental Oncology, "G. Pascale Foundation", IRCCS, Naples, Italy d.rea@istitutotumori.na.it.
Antonio
A
Luciano
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Davide
D
Liccardo
Department of Health Management, Pharmacy and Quality of Life, "G. Pascale Foundation", IRCCS, Naples, Italy.
Piera
P
Maiolino
Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Antonio
A
Cittadini
Scientific Direction, National Cancer Institute, "G. Pascale Foundation", IRCCS, Naples, Italy.
Gennaro
G
Ciliberto
Animal Facility Unit, Department of Experimental Oncology, "G. Pascale Foundation", IRCCS, Naples, Italy d.rea@istitutotumori.na.it.
Claudio
C
Arra
Cardiology Unit, "G. Pascale Foundation", IRCCS, Naples, Italy.
Nicola
N
Maurea
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D001696:Biomechanical Phenomena; D009202:Cardiomyopathies / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D066126:Cardiotoxicity / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects*; D004452:Echocardiography; D005260:Female; D006801:Humans; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
Strain; cardiotoxicity; chemotherapy; mouse model; speckle-tracking echocardiography