Background
—The precise molecular mechanism of Adriamycin-induced cardiomyopathy (ADR-CM) is still unknown. We address the demonstration of apoptotic myocardial cell death and the apoptosis-inducing molecules in ADR-CM induced in rats.
Methods and Results
—Until 8 weeks after the first administration of ADR, there was no increase in the number of labeled cells by terminal deoxynucleotidyl transferase assay (TUNEL method). Apoptotic indices increased significantly at weeks 9 and 10 in hearts of the ADR-treated group but not in those of the control group (0.42±0.12% versus 0.10±0.02% and 0.86±0.11% versus 0.09±0.04% at weeks 9 and 10, respectively). DNA ladder formation was also observed in the myocardial tissues during the late stages of the ADR-CM of rats. There was no significant difference in expression of
p53
gene between the ADR group and the control group at either the message or the protein level. An overexpression of Fas antigen was shown in myocardial cells of ADR-treated hearts at weeks 9 and 10 by both Western blotting and immunofluorescent staining. Furthermore, we confirmed that neutralization of anti–Fas ligand antibody inhibited ADR-induced apoptosis.
Conclusions
—Apoptotic cell death was observed in the hearts of ADR-CM rats, and the number of apoptotic myocardial cells increased with the deterioration of morphological findings and cardiac function, indicating that apoptosis may be an important mechanism of loss of myocardial cells and cardiac dysfunction in ADR-CM. Apoptosis in ADR-CM rats is not p53-dependent but rather is executed through a Fas-mediated pathway.
An 11-year-old girl with congenital atresia of the left coronary ostium underwent coronary artery bypass grafting using the internal mammary artery. Before surgery, the patient complained of syncope on exertion. Exercise electrocardiogram (ECG), two-dimensional echocardiogram, and 201Tl myocardial scintigram were useful in establishing the diagnosis. Selective coronary angiograms showed typical findings. Postoperative recovery was uneventful; exercise ECG and stress 201Tl myocardial scintigram demonstrated improvement. Internal mammary artery graft is probably better than a saphenous vein graft as a coronary artery bypass graft in childhood and adolescence because of the long-term patency of this type of graft.
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