APOPTOSIS IN MYOCYTES IN END-STAGE HEART-FAILURE

Background Heart failure can result from a variety of causes, includin g ischemic, hypertensive, toxic, and inflammatory heart disease. Howev er, the cellular mechanisms responsible for the progressive deteriorat ion of myocardial function observed in heart failure remain unclear an d may result from apoptosis (programmed cell death). Methods We examin ed seven explanted hearts obtained during cardiac transplantation for evidence of apoptosis, All seven patients had severe chronic heart fai lure: four had idiopathic dilated cardiomyopathy, and three had ischem ic cardiomyopathy, DNA fragmentation (an indicator of apoptosis) was i dentified histochemically by in situ end-labeling as well as by agaros e-gel electrophoresis of end-labeled DNA. Myocardial tissues obtained from four patients who had had a myocardial infarction one to two days previously were used as positive controls, and heart tissues obtained from Sour persons who died in motor vehicle accidents were used as ne gative controls for the end-labeling studies. Results Hearts from all four patients with idiopathic dilated cardiomyopathy and from one of t he three patients with ischemic cardiomyopathy had histochemical evide nce of DNA fragmentation, All four myocardial samples from patients wi th dilated cardiomyopathy also demonstrated DNA laddering, a character istic of apoptosis, whereas this was not seen in any of the samples fr om patients with ischemic cardiomyopathy. Histologic evidence of apopt osis was also observed in the central necrotic zone of acute myocardia l infarcts, but not in myocardium remote from the infarcted zone. Rare isolated apoptotic myocytes were seen in the myocardium from the four persons who died in motor vehicle accidents. Conclusions Loss of myoc ytes due to apoptosis occurs in patients with end-stage cardiomyopathy and may contribute to progressive myocardial dysfunction. (C) 1996, M assachusetts Medical Society.