title: Myocyte degeneration and cell death in hibernating human myocardium.
abstract: OBJECTIVE
  The aim of this study was to analyze the morphologic characteristics of myocyte degeneration leading to replacement fibrosis in hibernating myocardium by use of electron microscopy and immunohistochemical techniques.
  
  
  BACKGROUND
  Data on the ultrastructure and the cytoskeleton of cardiomyocytes in myocardial hibernation are scarce. Incomplete or delayed functional recovery might be due to variable degree of cardiomyocyte degeneration in hibernating myocardium.
  
  
  METHODS
  In 24 patients, regional wall motion abnormalities were analyzed by use of the centerline method before and 6 +/- 1 months after coronary artery bypass surgery. Preoperative technetium-99m sestamibi uptake was measured by single-photon emission computed tomography for assessing regional perfusion. Fluorine-18 fluorodeoxyglucose uptake was measured by positron emission tomography to assess glucose metabolism. Transmural biopsy specimens were taken during coronary artery bypass surgery from the center of the hypocontractile area of the anterior wall.
  
  
  RESULTS
  The myocytes showed varying signs of mild-to-severe degenerative changes and an increased degree of fibrosis. Immunohistochemical analysis demonstrated disruption of the cytoskeletal proteins titin and alpha-actinin. Electron microscopy of the cell organelles and immunohistochemical analysis of the cytoskeleton showed a similarity in the degree of degenerative alterations. Group 1 (n = 11) represented patients with only minor structural alterations, whereas group 2 (n = 13) showed severe morphologic degenerative changes. Wall motion abnormalities showed postoperative improvements, and nuclear imaging revealed a perfusion-metabolism mismatch without significant differences between the groups.
  
  
  CONCLUSIONS
  Long-term hypoperfusion causes different degrees of morphologic alterations leading to degeneration. Preoperative analysis of regional contractility and perfusion-metabolism imaging does not distinguish the severity of morphologic alterations nor the functional outcome after revascularization. The insufficient act of self-preservation in hibernating myocardium may lead to a progressive structural degeneration with an incomplete and delayed recovery of function after restoration of blood flow.
authors.affiliation: Department of Cardiology, Rheirisch-Westfälische Technische Hochschule University Hospital, Aachen, Germany.
authors.forename: E R
authors.initials: ER
authors.lastname: Schwarz
authors.forename: J
authors.initials: J
authors.lastname: Schaper
authors.forename: J
authors.initials: J
authors.lastname: vom Dahl
authors.forename: C
authors.initials: C
authors.lastname: Altehoefer
authors.forename: B
authors.initials: B
authors.lastname: Grohmann
authors.forename: F
authors.initials: F
authors.lastname: Schoendube
authors.forename: F H
authors.initials: FH
authors.lastname: Sheehan
authors.forename: R
authors.initials: R
authors.lastname: Uebis
authors.forename: U
authors.initials: U
authors.lastname: Buell
authors.forename: B J
authors.initials: BJ
authors.lastname: Messmer
authors.forename: W
authors.initials: W
authors.lastname: Schaper
authors.forename: P
authors.initials: P
authors.lastname: Hanrath
mesh_terms: D000328:Adult; D000368:Aged; D016923:Cell Death; D003599:Cytoskeleton / Q000648:ultrastructure; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000473:pathology* / Q000503:physiopathology; D009204:Myocardial Revascularization; D009206:Myocardium / Q000166:cytology* / Q000473:pathology / Q000648:ultrastructure; D013318:Stroke Volume