title: Hibernating myocardium: morphological correlates of inotropic stimulation and glucose uptake.
abstract: BACKGROUND
  In patients with postischaemic left ventricular dysfunction, segments recovering function after revascularisation (hibernating myocardium) may not respond during dobutamine echocardiography, despite preserved [(18)F] 2-fluoro-2-deoxy-D-glucose (FDG) uptake at positron emission tomography.
  
  
  OBJECTIVE
  To investigate whether this lack of response might reflect the degree of ultrastructural change in hibernating myocardium.
  
  
  METHODS
  Transmural biopsies were obtained from 22 dysfunctional segments in 22 patients during coronary artery bypass grafting and examined by light and electron microscopy. Wall motion scores and coronary vasodilator reserve were assessed before and after coronary artery bypass grafting (CABG).
  
  
  RESULTS
  Mean (SD) wall motion score improved in all segments following CABG (from 2.24 (0.4) to 1.55 (0.4); p < 0.0001), confirming hibernating myocardium. In these segments myocardial blood flow (positron emission tomography with H(2)(15)O) before CABG was similar to that in normal volunteers (1.02 (0.24) v 1.02 (0.23) ml/min/g), while the coronary vasodilator reserve was blunted (1.26 (0.7) v 3.2 (1.6); p < 0.0001). Myocardial blood flow was unchanged after CABG, whereas coronary vasodilator reserve increased to 2.10 (0.90) (p < 0.0007). In hibernating myocardium myofibrillar loss, interstitial fibrosis, and glycogen-rich myocytes were more marked than in control donor hearts. On the basis of the response to dobutamine before CABG, two functional groups were identified: group A, segments with inotropic reserve (n = 15); group B, segments without inotropic reserve (n = 7). FDG uptake was similar in group A and group B (0.40 (0.1) v 0.44 (0.1) micromol/min/g). In group B there was more myofibrillar loss (26 (8)% v 11 (5)%; p = 0.0009) and glycogen-rich myocytes (28 (11)% v 17 (10)%; p = 0.02), whereas interstitial fibrosis, myocardial blood flow, and coronary vasodilator reserve were similar in the two groups. Myofibrillar loss was the only independent predictor of inotropic reserve (p = 0.01).
  
  
  CONCLUSIONS
  Hibernating myocardium is characterised by a reduced coronary vasodilator reserve which improves on revascularisation and shows a spectrum of ultrastructural changes that influence the response to dobutamine, while FDG uptake is invariably preserved.
authors.affiliation: Cardiothoracic Surgical Unit, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: D
authors.initials: D
authors.lastname: Pagano
authors.forename: J N
authors.initials: JN
authors.lastname: Townend
authors.forename: D V
authors.initials: DV
authors.lastname: Parums
authors.forename: R S
authors.initials: RS
authors.lastname: Bonser
authors.forename: P G
authors.initials: PG
authors.lastname: Camici
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002316:Cardiotonic Agents; D001026:Coronary Artery Bypass; D003326:Coronary Circulation; D003327:Coronary Disease / Q000601:surgery; D004280:Dobutamine; D005260:Female; D019788:Fluorodeoxyglucose F18; D006333:Heart Failure / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D017682:Myocardial Stunning / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000648:ultrastructure*; D019275:Radiopharmaceuticals; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D004280:Dobutamine