doi:10.1016/j.ultrasmedbio.2007.08.002 ● Original Contribution MYOCARDIAL STRAIN ANALYSIS IN A DOXORUBICIN-INDUCED CARDIOMYOPATHY MODEL ELENA PIEGARI,* GIOVANNI DI SALVO, † BIAGIO CASTALDI, † MARIA REDENTA VITELLI,* GABRIELLA RODOLICO,* PAOLO GOLINO, † RAFFAELE CALABRÒ,* FRANCESCO ROSSI,* and LIBERATO BERRINO* *Department of Experimental Medicine and Excellence Research Centre for Cardiovascular Diseases, Second University of Naples; and † Department of Cardiology, Monaldi Hospital, Naples, Italy (Received 14 February 2007, revised 30 July 2007, in final form 2 August 2007) Abstract—The aim of our study was to determine if strain (S) and strain rate (SR) imaging are more sensitive indices with respect to standard echocardiographic parameters to assess cardiac function in an experimental model of doxorubicin (DOX)-induced cardiomyopathy. DOX was administered intraperitoneally 4/wk at the dose of 1.25 mg/kg/d over four weeks in Wistar rats (n  26). Other 14 Wistar rats were used as controls. Echocardiographic studies were performed before DOX treatment (baseline), after two and four weeks of treatment. At two and four weeks of DOX treatment, rat hearts were collected for histologic analysis. After two weeks of DOX treatment, there were no significant changes in standard echocardiographic parameters and in myocardial velocities, but after four weeks of treatment, ejection fraction significantly decreased and left ventricle dimensions significantly increased. Also, myocardial velocities were significantly reduced after four weeks of treatment. Conversely, S and SR values changed significantly already after two weeks of treatment. At baseline, S and SR values were 27  7% and 7.4  1.7, respectively, and they significantly decreased to 12  6% (p < 0.0001) and 6  1.5 (p < 0.005) at two weeks of treatment. These changes were also significant compared with control rat parameters (p < 0.001). At four weeks of DOX treatment, a progressive worsening occurred. Strain and SR further significantly decreased to 10  4% (p < 0.0001 vs. baseline) and 4.6  1.6 (p < 0.0001 vs. baseline), respectively. These changes were supported by histologic findings. Indeed, damage in myocardial tissue was demonstrated by histology already after two weeks of DOX treatment, with a damage progression after four weeks of treatment. Our data demonstrate that S and SR imaging are more sensitive indices in identifying early myocardial systolic changes induced by DOX than standard echocardiographic parameters and myocardial velocities. We believe that our model will be very supportive to further assess these new diagnostic strategies to provide a precocious diagnosis of LV dysfunction with a unique opportunity to initiate preventive cardioactive therapy. (E-mail: giodisal@yahoo.it) © 2008 World Federation for Ultrasound in Medicine & Biology. Key Words: Anthracyclines, Cardiomyopathy, Echocardiography, Strain rate imaging, Tissue Doppler. INTRODUCTION Anthracyclines, a family of chemotherapeutic agents, are the most frequent cause of iatrogenic congestive heart failure ranging from acute reversible minor to irrevers- ible reduction in the LV ejection fraction (EF) and death despite preventive measures (Lipshultz et al. 1991). Car- diac abnormalities can occur after a single dose or months/years after withdrawal of therapy with anthracy- clines. Although most of congestive heart failures oc- curred within the first year after therapy, late deteriora- tion has been observed up to more than a decade after the treatment, especially in long-term survivors of childhood cancer (Lipshultz et al. 1991; Goorin et al. 1990; Stein- herz et al. 1991). The exact mechanism underlying anthracycline-in- duced cardiotoxicity has not been fully elucidated, but evidences suggest that a free radical production increase and a myocardial endogenous antioxidant decrease play an important role in the pathogenesis of heart failure. Apoptosis and hyperlipidemia may also be involved in this process (Minotti et al. 2004; Singal and Iliskovic 1998). At present, serial surveillance for cardiotoxicity in patients receiving anthracyclines has most commonly centered on the assessment of LV systolic function by standard echocardiography (Lipshultz et al. 1991), even Address correspondence to: Giovanni Di Salvo, Department of Cardiology, Monaldi Hospital, Naples, Italy. E-mail: giodisal@yahoo.it Ultrasound in Med. & Biol., Vol. 34, No. 3, pp. 370 –378, 2008 Copyright © 2008 World Federation for Ultrasound in Medicine & Biology Printed in the USA. All rights reserved 0301-5629/08/$–see front matter 370