title: Apoptosis in myocytes in end-stage heart failure.
abstract: BACKGROUND
  Heart failure can result from a variety of causes, including ischemic, hypertensive, toxic, and inflammatory heart disease. However, the cellular mechanisms responsible for the progressive deterioration of myocardial function observed in heart failure remain unclear and may result from apoptosis (programmed cell death).
  
  
  METHODS
  We examined seven explanted hearts obtained during cardiac transplantation for evidence of apoptosis. All seven patients had severe chronic heart failure: four had idiopathic dilated cardiomyopathy, and three had ischemic cardiomyopathy. DNA fragmentation (an indicator of apoptosis) was identified histochemically by in situ end-labeling as well as by agarose-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 four persons who died in motor vehicle accidents were used as negative controls for the end-labeling studies.
  
  
  RESULTS
  Hearts from all four patients with idiopathic dilated cardiomyopathy and from one of the three patients with ischemic cardiomyopathy had histochemical evidence of DNA fragmentation. All four myocardial samples from patients with dilated cardiomyopathy also demonstrated DNA laddering, a characteristic of apoptosis, whereas this was not seen in any of the samples from patients with ischemic cardiomyopathy. Histological evidence of apoptosis was also observed in the central necrotic zone of acute myocardial 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 myocytes due to apoptosis occurs in patients with end-stage cardiomyopathy and may contribute to progressive myocardial dysfunction.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston 02115, USA.
authors.forename: J
authors.initials: J
authors.lastname: Narula
authors.forename: N
authors.initials: N
authors.lastname: Haider
authors.forename: R
authors.initials: R
authors.lastname: Virmani
authors.forename: T G
authors.initials: TG
authors.lastname: DiSalvo
authors.forename: F D
authors.initials: FD
authors.lastname: Kolodgie
authors.forename: R J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: U
authors.initials: U
authors.lastname: Schmidt
authors.forename: M J
authors.initials: MJ
authors.lastname: Semigran
authors.forename: G W
authors.initials: GW
authors.lastname: Dec
authors.forename: B A
authors.initials: BA
authors.lastname: Khaw
mesh_terms: D000063:Accidents, Traffic; D000293:Adolescent; D017209:Apoptosis; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000503:physiopathology; D002908:Chronic Disease; D004249:DNA Damage; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*
chemical_list: D004253:DNA Nucleotidylexotransferase