Sex-dependent differences in cardiac function and strain in doxorubicin-induced cardiomyopathy

Doxorubicin is a chemotherapeutic agent used to treat many types of cancer. While effective, doxorubicin can cause cardiomyopathy, a disease affecting the heart muscle. Although the effects of doxorubicin on the heart are well studied, the mechanisms leading to cardiomyopathy are not well understood. Previous studies have used murine models to study the cardiotoxicity of doxorubicin. These reports showed that cardiac dysfunction is more pronounced in male compared to female mice. The goal of this study is to further evaluate sex differences in doxorubicin induced cardiomyopathy using 4-dimensional strain mapping techniques. In this study, both female and male C57Bl/6J mice received weekly imaging and injections of doxorubicin (4 mg/kg) for 4 weeks, followed by weekly imaging for 5 weeks. Two-dimensional (2D) and four-dimensional ultrasound (4DUS) images were acquired using the Vevo 3100 ultrasound system (FUJIFILM VisualSonics) allowing visualization of the heart in vivo over the course of the study. These 4DUS images were analyzed using 4D strain tracking software, providing more accurate and detailed regional measures of cardiac dysfunction than achieved from 2D images alone. The expected findings of this study are that female C57Bl/6J mice will have less severe outcomes based on previous studies. Subtle changes in cardiac strain and function not seen in traditional ultrasound methods may be observed, explaining the mechanism by which doxorubicin leads to sex dependent differences in cardiomyopathy. The sex-specific findings from this study have the potential to improve patient-specific treatment for doxorubicin-induced cardiomyopathy.