Structural and Electrophysiological Changes in a Model of Cardiotoxicity Induced by Anthracycline Combined With Trastuzumab

Abstract

These results suggest that <i>in vivo</i> Dox but not Trz administration causes T-tubule disarray and pronounced changes in electrical activity of CMs. While adaptive changes may account for normal AP shape and reduced DADs late after Dox administration, subsequent Trz administration interferes with such adaptive changes. Intracellular Ca²⁺ handling was differently affected by Dox and Trz treatment, leading to SR instability in both cases. These findings illustrate the specific roles of Dox and Trz, and their interactions in cardiotoxicity and arrhythmogenicity.