Histologic and ultrastructural analyses of the cross-sections of hearts from AAV-CMVGFP– and AAV-HREEpo–treated Epo-TAg^h and healthy mice.

(A-D) Histologic analyses. (E-H) Ultrastructural analyses. (A,E) Healthy heart. (B,F) Epo-TAg^h heart showing enlargement/hypertrophy illustrated by the increased size of the heart and the increase in sarcomere length. (C,G) Healthy heart treated with AAV-HREEpo. (D,H) Epo-TAg^h heart showing partial correction of the hypertrophy such that there is a decrease in the sarcomere length compared with the untreated Epo-TAg^hhearts. Note the reduction in the width of the left ventricle wall in panel D (AAV-HREEpo–treated Epo-TAg^h mouse) compared with panel B (untreated mouse). LV indicates left ventricle; RV, right ventricle; M, mitochondria; I, I band of the striated cardiac muscle cell (the distance between these I bands is the sarcomere). Sarcomere length in anemic mice was 1.20 ± 0.20 μm, and in anemic mice treated with AAV-HREEpo it was 1.05 ± 0.08 μm (P = .0001), showing that the decrease in sarcomere length between these hearts was statistically significant. Original magnifications: × 12.5 for histologic analysis, × 2100 for ultrastructural analysis.