FIGURE 1.

Doxorubicin (Dox)‐induced juvenile mouse cardiotoxicity model. (A) Schematic representation of the study design to assess acute Dox‐induced cardiotoxicity using nude or Balb/c mice (n = 8 in each group). Four‐week‐old mice were randomly divided into four groups: control, exercise alone, Dox alone, or Dox + Exer. All mice were treated by tail vein with phosphate‐buffered saline or Dox twice per week for 2 weeks. The exercise regimen was 45 min treadmill walking/day, 5 days/week. Echocardiography was conducted before treatment and 24 h after the final dose of Dox. Mice were killed 48 h after the final dose of Dox. (B) To assess Dox‐induced late cardiotoxicity, mice were treated for 2 weeks as in A and then followed them for 12 weeks after therapy. Echocardiography evaluation was done before and 24 h after therapy and then at 2, 4, 8, and 12 weeks following therapy (n = 10 in each group). (C) To assess the effect of initiating exercise after Dox therapy, mice were treated with or without Dox. The exercise protocol described in A was initiated 24 h after therapy. Echocardiography evaluation was done before and 24 h after therapy and then at 2, 4, 8, and 12 weeks after therapy (n = 10 in each group). Dox + Exer indicates doxorubicin + exercise