title: Severe energy deprivation of human hibernating myocardium as possible common pathomechanism of contractile dysfunction, structural degeneration and cell death.
abstract: OBJECTIVE
  We tested the hypothesis that severe alterations in myocardial energy metabolism play an important role in the pathophysiology of human hibernating myocardium (HHM).
  
  
  BACKGROUND
  It is well established that a disturbed myocardial energy metabolism results in impairments of contractile performance, structure and viability. All of these are important characteristics of HHM.
  
  
  METHODS
  In 16 patients with documented coronary artery disease and impaired left ventricular function, HHM was preoperatively detected by thallium-201 scintigraphy, radionuclide ventriculography and low-dose dobutamine echocardiography. These regions were validated as HHM by their recovery of contractile function three months following revascularization. During open-heart surgery, transmural biopsies were removed from the hibernating areas and analyzed both biochemically and morphologically. These findings were compared to normal human myocardium. All metabolite contents given were normalized for the degree of fibrosis (control: 9.8 +/- 0.5%; HHM: 28.1 +/- 3.0%; p < 0.05), providing myocellular contents.
  
  
  RESULTS
  In HHM, decreased contents (micromol/g wet weight) in adenosine triphosphate (ATP) (control: 4.17 +/- 0.26; HHM: 1.72 +/- 0.25; p < 0.001), creatine phosphate (5.67 +/- 0.70 vs. 0.84 +/- 0.13; p < 0.001) and creatine (27.6 +/- 3.19 vs. 11.2 +/- 1.56; p < 0.0001) were found, but contents in lactate (2.22 +/- 0.26 vs. 25.38 +/- 3.53; p < 0.001), purine bases (0.58 +/- 0.09 vs. 1.26 +/- 0.13; p < 0.001) and protons (pH units: 7.199 +/- 0.01 vs. 6.59 +/- 0.07; p < 0.001) were increased. Levels in adenosine diphosphate, adenosine monophosphate and inorganic phosphate remained unchanged. Energy depletion in HHM was reflected by decreases in the free energy of ATP hydrolysis and in energy charge.
  
  
  CONCLUSIONS
  These data confirm our hypothesis that HHM is energy-depleted myocardium, exhibiting signs of chronic reduction in resting blood flow and a downregulation of energy turnover. The alterations in energy metabolism observed may become operative in triggering and maintaining contractile dysfunction, continuous tissue degeneration and cardiomyocyte loss.
authors.affiliation: Department of Cardiology, University of Freiburg, Freiburg, Germany. elaesser@med1.ukl.uni-freiburg.de
authors.forename: Albrecht
authors.initials: A
authors.lastname: Elsässer
authors.forename: Klaus Detlev
authors.initials: KD
authors.lastname: Müller
authors.forename: Woitek
authors.initials: W
authors.lastname: Skwara
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kübler
authors.forename: Achim M
authors.initials: AM
authors.lastname: Vogt
mesh_terms: D000368:Aged; D000818:Animals; D001706:Biopsy; D002470:Cell Survival; D003326:Coronary Circulation / Q000502:physiology; D004452:Echocardiography; D004734:Energy Metabolism; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D017682:Myocardial Stunning / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011877:Radionuclide Imaging