Myocardial cell death in fibrillating and dilated human right atria

OBJECTIVES The aim of the present study was to determine if myocytes can di e by apoptosis in fibrillating and dilated human atria. BACKGROUND The cellular remodeling that occurs during atrial fibrillation ( AF) may reflect a degree of dedifferentiation of the atrial myocardium, a p rocess that may be reversible. METHODS We examined human right atrial myocardium specimens (n = 50) for th e presence of apoptotic myocytes. We used immunohistochemical and Western b lotting analysis to examine the expression of a final effector of programme d cell death, caspase-3 (CASP-3) and of regulatory proteins from the BCL-2 family. RESULTS Sections from atria in AF contained a high percentage of large myoc ytes with a disrupted sarcomeric apparatus replaced by glycogen granules (6 4.4 +/- 6.3% vs. 12.2 +/- 5.8%). These abnormal myocytes, which also predom inated in atria from hearts with decreased left ventricular ejection fracti on (42.3 +/- 10.1%), contained large nuclei, most of which were TUNEL posit ive, indicating a degree of DNA breakage. None of these abnormal myocytes e xpressed the proliferative antigen Ki-67. A small percentage of the enlarge d nuclei (4.2 +/- 0.8%) contained condensed chromatin and were strongly TUN EL positive. Both the pro- and activated forms of CASP-3 were detected in d iseased myocardial samples, which also showed stronger CASP-3 expression th an controls. Expression of the antiapoptotic BCL-2 protein was decreased in diseased atria, whereas that of the proapoptotic BAX protein remained unch anged. CONCLUSIONS In fibrillating and dilated atria, apoptotic death of myocytes with myolysis contributes to cellular remodeling, which may not be entirely reversible. (C) 1999 by the American College of Cardiology.