Domenica Rea1, Carmela Coppola2, Antonio Barbieri1, Maria Gaia Monti3, Gabriella Misso4, Giuseppe Palma1, Sabrina Bimonte5, Mayra Rachele Zarone4, Antonio Luciano1, Davide Liccardo4, Piera Maiolino6, Antonio Cittadini3, Gennaro Ciliberto7, Claudio Arra1, Nicola Maurea2. 1. Animal Facility Unit, Department of Experimental Oncology, "G. Pascale Foundation", IRCCS, Naples, Italy d.rea@istitutotumori.na.it. 2. Cardiology Unit, "G. Pascale Foundation", IRCCS, Naples, Italy. 3. Department of Translational Medical Sciences, Federico II University, Naples, Italy. 4. Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. 5. Division of Abdominal Surgical Oncology, Hepatobiliary Unit, "G. Pascale Foundation", IRCCS, Naples, Italy. 6. Department of Health Management, Pharmacy and Quality of Life, "G. Pascale Foundation", IRCCS, Naples, Italy. 7. Scientific Direction, National Cancer Institute, "G. Pascale Foundation", IRCCS, Naples, Italy.
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.
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.
Authors: Claudio de Lucia; Markus Wallner; Deborah M Eaton; Huaqing Zhao; Steven R Houser; Walter J Koch Journal: J Gerontol A Biol Sci Med Sci Date: 2019-03-14 Impact factor: 6.053
Authors: Igor L Gomes-Santos; Camila P Jordão; Clevia S Passos; Patricia C Brum; Edilamar M Oliveira; Roger Chammas; Anamaria A Camargo; Carlos E Negrão Journal: Front Cardiovasc Med Date: 2021-04-01
Authors: Aynur Acibuca; Ahmet Sezer; Mustafa Yilmaz; Ahmet Taner Sumbul; Senol Demircan; Ibrahim Haldun Muderrisoglu; Ozgur Ozyilkan Journal: J Int Med Res Date: 2021-12 Impact factor: 1.671
Authors: Vincenzo Quagliariello; Margherita Passariello; Annabella Di Mauro; Ciro Cipullo; Andrea Paccone; Antonio Barbieri; Giuseppe Palma; Antonio Luciano; Simona Buccolo; Irma Bisceglia; Maria Laura Canale; Giuseppina Gallucci; Alessandro Inno; Claudia De Lorenzo; Nicola Maurea Journal: Front Cardiovasc Med Date: 2022-09-08