Decoupling the biomechanical effects of epirubicin on male rat myocardium: a dual analysis of active contractile function and passive material properties

Anthracycline chemotherapy, a common treatment for cancer, has shown remarkable efficacy in combating malignant cells. However, it is known to have undesirable side effects on the heart, collectively referred to as cardiotoxicity, which limits the applicability of such drugs as they can cause irreversible left ventricular dysfunction. This research quantitatively investigates the mechanical effects of epirubicin (EPI) on cardiac contractility using a dual-pronged analytical approach. Active contractile function was assessed via a robust statistical analysis of the experimentally measured active forces, while passive tissue properties were characterized by calibrating the Yeoh hyperelastic constitutive model to experimental stress-strain data. This approach was chosen to provide a direct, functional measure of contractile impairment while simultaneously deriving a single, objective material parameter ( C10 ) for intrinsic tissue stiffness. The findings reveal a statistically significant ( p<0.001 ) and profound reduction in active forces by 66.3% in the EPI group. Crucially, the constitutive model reveals a significant increase in passive myocardial stiffness, evidenced by a 10.5% increase in the initial shear modulus derived from the C10 parameter. Together, these results provide a definitive functional benchmark of contractile loss and a core material parameter for stiffness, offering a comprehensive dataset for validating future in silico models of cardiotoxicity.