The ErbB2-antibody 2C4 and cardiac dysfunction in mice.

Abstract

e11040 Background: Anti-ErbB2 therapies are associated with increased risk of left ventricular (LV) dysfunction. Trastuzumab increases the frequency of asymptomatic decrease in LV ejection fraction (LVEF) by 3-18%, and the risk of heart failure (HF) by 2-4%. The newer ErbB2 antibody rhuMAb 2C4 (pertuzumab) seems to affect ligand induced ErbB signaling in a more direct fashion, affecting EGFR/ErbB2 dimerization; yet, its cardiac side effects are only beginning to emerge. Here, we test whether the murine 2C4 induces cardiac dysfunction in normal mice. Methods: In vivo cardiac function was measured with LV fractional shortening (FS) by M-mode echocardiography in sedated C57BL/6 mice (2-4 mo. old) at day 0, and after 2 and 6 days of daily i.p. administration of 2C4 (2.25 μg/g/day) or doxorubicin (Doxo, 2.17 μg/g/day) as a positive control, and in sham animals. With Speckle Tracking echocardiography (ST) we also evaluated radial myocardial strain (%), a very sensitive parameter which can predict LV dysfunction...