title: Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model: contribution of the new tool 2D-speckle tracking.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Coppola
authors.affiliation: Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Riccio
authors.affiliation: Animal Facility Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Barbieri
authors.affiliation: Department of Translational Medical Sciences, University Federico II, Naples, Italy.
authors.forename: Maria Gaia
authors.initials: MG
authors.lastname: Monti
authors.affiliation: Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Piscopo
authors.affiliation: Animal Facility Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Rea
authors.affiliation: Animal Facility Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.affiliation: Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Maurea
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy; CEINGE Biotecnologie Avanzate, Naples, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: De Lorenzo
authors.affiliation: Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Maurea
keywords: ErbB2/Her2; breast cancer; cardiotoxicity; doxorubicin; trastuzumab