TY - JOUR
T1 - Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model
T2 - Contribution of the new tool 2D-speckle tracking
AU - Coppola, Carmela
AU - Riccio, Gennaro
AU - Barbieri, Antonio
AU - Monti, Maria Gaia
AU - Piscopo, Giovanna
AU - Rea, Domenica
AU - Arra, Claudio
AU - Maurea, Carlo
AU - De Lorenzo, Claudia
AU - Maurea, Nicola
PY - 2016/11/2
Y1 - 2016/11/2
N2 - Objective: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage. Methods: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response. Results: Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P,0.01). Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional shortening reduction and cardiac fibrosis were observed only after 7 days of trastuzumab treatment, in contrast to doxorubicin treatment which induced early fibrosis and fractional shortening reduction. Conclusion: The reduction of left ventricular systolic strain after 2 days of trastuzumab treatment may indicate early myocardial functional damage before the reduction in left ventricular ejection fraction and this early dysfunction is well correlated with structural myocardial damage, such as apoptosis and inflammatory response. Fractional shortening reduction after 7 days of trastuzumab treatment is related to fibrosis in cardiac tissue.
AB - Objective: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage. Methods: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response. Results: Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P,0.01). Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional shortening reduction and cardiac fibrosis were observed only after 7 days of trastuzumab treatment, in contrast to doxorubicin treatment which induced early fibrosis and fractional shortening reduction. Conclusion: The reduction of left ventricular systolic strain after 2 days of trastuzumab treatment may indicate early myocardial functional damage before the reduction in left ventricular ejection fraction and this early dysfunction is well correlated with structural myocardial damage, such as apoptosis and inflammatory response. Fractional shortening reduction after 7 days of trastuzumab treatment is related to fibrosis in cardiac tissue.
KW - Breast cancer
KW - Cardiotoxicity
KW - Doxorubicin
KW - ErbB2/Her2
KW - Trastuzumab
UR - http://www.scopus.com/inward/record.url?scp=84994476391&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994476391&partnerID=8YFLogxK
U2 - 10.2147/OTT.S106528
DO - 10.2147/OTT.S106528
M3 - Article
AN - SCOPUS:84994476391
VL - 9
SP - 6785
EP - 6794
JO - OncoTargets and Therapy
JF - OncoTargets and Therapy
SN - 1178-6930
ER -