Adipose Tissue Dysfunction as a Novel Contributor to Heart Failure Following Recovery from Doxorubicin Treatment

Doxorubicin (DOX) remains a cornerstone of cancer treatment but is limited by its dose-dependent cardiotoxicity, and clinical care for cancer survivors has not yet overcome the poor prognosis of DOX-induced heart failure (HF). PURPOSE: To identify early events that are associated with HF development in rats treated with DOX. METHODS: 42 Male Wistar rats received either DOX (4 weekly I.P. injections of 2.5mg/Kg; D, n=24) or equal volume of saline solution (C, n=18). Rats were evaluated after DOX treatment – baseline timepoint (CB or DB) and following 6 weeks of recovery – final timepoint (CF or DF). RESULTS: No animals died during DOX treatment; however, mortality during recovery was 33.33% in the DOX group (6 rats). Cardiac injury was assessed by plasma concentrations of the biomarker NT-proBNP and did not differ between groups at baseline timepoint but was significantly elevated at the recovery timepoint in DF group compared to CF (CB: 334±96.7, CF: 334±89.5, DB: 405±123, DF:607±166 pg/mL, p