title: Ultrastructural evidence of increased tolerance of hibernating myocardium to cardioplegic ischemia-reperfusion injury.
abstract: OBJECTIVE
  The goal of this study was to investigate the effects of ischemia-reperfusion on myocardial ultrastructure in patients with and without hibernating myocardium.
  
  
  BACKGROUND
  It is generally accepted that chronically dysfunctional, hibernating myocardium may remain nonetheless viable for a long time. It has been postulated that hibernating myocytes may survive, despite being subtended by a severe coronary artery stenosis, as they might be less susceptible to ischemic insults. However, whether hibernating myocardium is indeed more resistant to ischemia has never been investigated.
  
  
  METHODS
  Myocardial biopsies were taken before cardiac arrest and after reperfusion from the anterior wall of the left ventricle in patients undergoing coronary artery bypass surgery, divided according to presence (n = 7) or absence (n = 7) of hibernating myocardium. Ultrastructural changes were studied by electron microscopy. Because ischemia-reperfusion injury is related to oxidative stress, we also evaluated coronary sinus concentration of the antioxidants alpha-tocopherol, beta-carotene, and ubiquinol, and of lipid peroxidation products pre-ischemia and after reperfusion.
  
  
  RESULTS
  Both groups were similar with respect to length of ischemia and changes in the various indexes of oxidative stress. In normally contracting myocardium, ischemia/reperfusion induced moderate overall ultrastructural changes, and marked alterations at the mitochondrial level. In contrast, post-reperfusion biopsies of hibernating myocardium displayed only minor overall ultrastructural changes, and scored significantly better on mitochondrial damage.
  
  
  CONCLUSIONS
  Despite similar severity of ischemia/reperfusion, hibernating myocardium showed significantly less ultrastructural evidence of cell injury compared with normally contracting myocardium. These data indicate that human hibernating myocardium is intrinsically more resistant to ischemia/reperfusion injury.
authors.affiliation: Instituto de Investigaciones Cardiológicas (ININCA), Department of Medicine, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: José
authors.initials: J
authors.lastname: Milei
authors.forename: César G
authors.initials: CG
authors.lastname: Fraga
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Grana
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ferreira
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ambrosio
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000503:physiopathology / Q000601:surgery; D005500:Follow-Up Studies; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008854:Microscopy, Electron; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D017682:Myocardial Stunning / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018384:Oxidative Stress / Q000502:physiology; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D013318:Stroke Volume / Q000502:physiology; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology / Q000601:surgery
chemical_list: D000975:Antioxidants; D015415:Biomarkers