title: Abnormalities of cardiocytes in regions bordering fibrous scars of dogs with heart failure.
abstract: Progressive deterioration of left ventricular function is a characteristic feature of the heart failure state and is often speculated to result from ongoing loss of viable myocytes. We previously showed that in dogs with chronic heart failure, cardiocyte death through apoptosis occurs in the border region of fibrous scars (old infarcts). In the present study we examined the structural integrity of cardiocytes in regions bordering fibrous scars using transmission electron microscopy. Morphometric studies were performed using left ventricular tissue obtained from ten dogs with chronic heart failure produced by intracoronary microembolizations. Mitochondrial number increased significantly with proximity to the scar, while mitochondrial size decreased leading to a gradual decrease in mitochondrial volume fraction. Severe injury to mitochondria was present in only 5% of organelles in myocytes far from the scar but increased markedly to 28-41% in myocytes adjacent to or incorporated within the scar. Similarly, severe myofibrillar abnormalities were present in only 3% of myocytes that were far from the scar but increased significantly to 12-73% in myocytes adjacent to or incorporated within the scar. These results indicate that in dogs with chronic heart failure, constituent myocytes of left ventricular regions bordering fibrous scars manifest heterogeneity in the extent of degeneration. The extent of degeneration is greatest in myocytes closest to the scar and least in myocytes far from the scar. We postulate that this wavefront of myocyte degeneration is a dynamic process that may lead to progressive expansion of the scar through loss of viable myocytes and ultimately may contribute, in part, to the progressive left ventricular dysfunction that characterizes the heart failure state.
authors.affiliation: Department of Medicine, Henry Ford Heart and Vascular Institute, Detroit, MI 48202, USA.
authors.forename: V G
authors.initials: VG
authors.lastname: Sharov
authors.forename: H N
authors.initials: HN
authors.lastname: Sabbah
authors.forename: A S
authors.initials: AS
authors.lastname: Ali
authors.forename: H
authors.initials: H
authors.lastname: Shimoyama
authors.forename: M
authors.initials: M
authors.lastname: Lesch
authors.forename: S
authors.initials: S
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D048429:Cell Size; D002921:Cicatrix / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D004617:Embolism / Q000150:complications; D005355:Fibrosis / Q000473:pathology; D006333:Heart Failure / Q000209:etiology / Q000473:pathology*; D006352:Heart Ventricles / Q000473:pathology*; D008854:Microscopy, Electron; D008863:Microspheres; D008929:Mitochondria, Heart / Q000648:ultrastructure; D009206:Myocardium / Q000648:ultrastructure*; D012518:Sarcomeres / Q000648:ultrastructure