FIGURE 6.

Exercise during doxorubicin (Dox) therapy prevented late Dox‐induced cardiotoxicity in nude mice 12 weeks after therapy. (A) Quantitative analysis of autophagosomes in the heart tissue. Twelve weeks after therapy, control versus Dox, p = 0.0014; Dox versus Dox + Exer, p = 0.0281. Statistical analysis as described in Figure 2. (B) Representative transmission electron microscopy (TEM) images of cardiac vessels. P indicates pericytes and E, endothelial cells. (C) Representative TEM images of abnormal mitochondria (arrow) and vacuolization (asterisk). (D, E) Collagen deposition in the left ventricle was determined using Masson trichrome staining after therapy completion (D) and 12 weeks after therapy (E). wks indicates weeks. Scale bar: 100 μm. (F) Quantification of collagen deposition by percentage collagen volume fraction (CVF%). Control versus Dox, ****p < 0.0001; Dox versus Dox + Exer, p = 0.0007 by two‐factor repeated‐measures ANOVA. (G, H) Change in mitral valve E and A velocity 12 weeks after therapy. (I) Representative echocardiography images of the E and A peak. (J) The E/A ratio was measured for each mouse (n = 9 in each group)