title: Chronic hibernating myocardium in sheep can occur without degenerating events and is reversed after revascularization.
abstract: BACKGROUND
  Our goal was to show that blunting of myocardial flow reserve is mainly involved in adaptive chronic myocardial hibernation without apparent cardiomyocyte degeneration.
  
  
  RESULTS
  Sheep chronically instrumented with critical multivessel stenosis and/or percutaneous transluminal coronary angioplasty (PTCA)-induced revascularization were allowed to run and feed in the open for 2 and 5 months, respectively. Regional myocardial blood flow (MBF) with colored microspheres, regional and global left ventricular function and dimensions (2D echocardiography), and myocardial structure were studied. In sheep with a critical stenosis, a progressive increase in left ventricular end-diastolic and end-systolic cavity area and a decrease in fractional area change were found. Fraction of wall thickness decreased in all left ventricular wall segments. MBF was slightly but not significantly decreased at rest at 2 months. Morphological quantification revealed a rather small but significant increase in diffusely distributed connective tissue, cardiomyocyte hypertrophy, and presence of viable myocardium of which almost 30 % of the myocytes showed depletion of sarcomeres and accumulation of glycogen. The extent of myolysis in the transmural layer correlated with the degree of left ventricular dilation. Structural degeneration of cardiomyocytes was not observed. Balloon dilatation (PTCA) of one of the coronary artery stenoses at 10 weeks revealed recovery of fraction of wall thickness and near normalization of global subcellular structure at 20 weeks.
  
  
  CONCLUSIONS
  These data indicate that chronic reduction of coronary reserve by itself can induce ischemic cardiomyopathy characterized by left ventricular dilatation, depressed regional and global function, adaptive chronic myocardial hibernation, reactive fibrosis and cardiomyocyte hypertrophy in the absence of obvious degenerative phenomena.
  
  
  CONCLUSIONS
  Reduction of myocardial flow reserve due to chronic coronary artery stenosis in sheep induces adaptive myocardial hibernation without involvement of degenerative phenomena.
authors: CARIM, Maastricht University, Maastricht, The Netherlands; Electron Microscopy Unit at CRISP; Department of Molecular Cell Biology. Electronic address: f.verheyen@maastrichtuniversity.nl.
authors: F
authors: F
authors: Verheyen
authors: Department of Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: R
authors: R
authors: Racz
authors: CARIM, Maastricht University, Maastricht, The Netherlands; Department of Molecular Cell Biology.
authors: M
authors: M
authors: Borgers
authors: CARIM, Maastricht University, Maastricht, The Netherlands; Department of Experimental Cardiology, KU Leuven, Leuven, Belgium.
authors: R B
authors: RB
authors: Driesen
authors: CARIM, Maastricht University, Maastricht, The Netherlands; Electron Microscopy Unit at CRISP.
authors: M-H
authors: MH
authors: Lenders
authors: Department of Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: W J
authors: WJ
authors: Flameng
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003326:Coronary Circulation; D023921:Coronary Stenosis / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005355:Fibrosis; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D017682:Myocardial Stunning / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D062645:Percutaneous Coronary Intervention; D012720:Severity of Illness Index; D012756:Sheep; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left
keywords: Cardiomyopathy; Coronary artery stenosis; Hibernation; Morphology; Myocardial blood flow