Figure 4

Histoanatomical findings of βMHC-rae28 with heart failure. A, External appearances of the hearts are shown in the upper panels. The anterior thoracic wall was removed to allow the interior of thoracic chamber to be observed. Transverse sections with hematoxylin-eosin stain are shown in the lower panels. The hearts were removed from wild-type and 7-month-old βMHC-rae28 and were examined histologically. Note marked dilation and reduced wall thickness in both of the ventricles and massive pleural effusion in βMHC-rae28. Wt = Wild type. Scale bar, 2 mm. B, Electron microscopic analysis of the ventricular myocardium of 3-month-old wild type and βMHC-rae28. In contrast to the regular arrays of the wild-type sarcomeres, irregularity of the mutant myofibrils are prominent. Shown in βMHC-rae28 is a so-called giant mitochondrion (Ghadially, 1988), which was not found in the wild-type hearts. We observed similar findings in 6-month-old βMHC-rae28 (not shown). C, TUNEL staining of the hearts from the 3- and 6-month-old wild type and βMHC-rae28. The sections from these hearts were stained with the TUNEL method (upper panels) and with 4,6-diamidino-2-phenylindole (lower panels). TUNEL-positive cardiomyocytes were detected in 3-month-old βMHC-rae28 and had remarkably increased in the 6-month-old animals. D, DNA ladder analysis. High molecular weight DNAs were isolated and analyzed by 1% agarose electrophoresis. M = Molecular marker; wt = Wild-type heart; βMHC-rae28 = βMHC-rae28 heart.