Effect of ranolazine administered after trastuzumab treatment on cardiotoxicity in mice.

597 Background: Trastuzumab (T), a monoclonal antibody against ErbB2, has improved the prognosis of breast cancer patients, but ErbB2 blockade in cardiomyocytes can produce asymptomatic left ventricular dysfunction and heart failure, whose mechanism has not been elucidated and can include changes in Ca2+ regulation. We aim at assessing whether Ranolazine (R), an inhibitor of the late sodium current, administered after T treatment, blunts T cardiotoxicity in vivo and in vitro. Methods: In vitro, rat H9C2 cardiomyoblasts were treated with T (0.2µM) for 3 days and then treated in the absence or presence of R (1µM or 10μM) for 3 days. In vivo, fractional shortening (FS) and ejection fraction (EF) were measured by M-mode echocardiography and radial and longitudinal strain (RS and LS) were measured using 2D speckle-tracking, in C57/BL6 mice, at 0, 2 and after 7 days of daily administration of T (2.25 mg/kg/day). These measurements were repeated after 5 days of R treatment (305 mg/Kg/day) initiated at the end of...