Biochemical mechanisms of hibernation and stunning in the human heart

Cardiovasc Res. 2002 Dec;56(3):411-21. doi: 10.1016/s0008-6363(02)00596-5.


Background: Myocardial hibernation and stunning are characterized by depressed cardiac function in the presence of reduced or normal coronary blood flow. The underlying biochemical mechanisms are widely unknown and only limited data are available in human hearts.

Methods and results: Left ventricular transmural myocardial biopsies were obtained from normal and dysfunctional segments of patients undergoing coronary bypass surgery. Segments were classified as hibernating (n=10) or stunned (n=9) using contrast ventriculography and echocardiography, single photon emission computed tomography (SPECT), and positron emission tomography (PET). In each patient, biopsies from normal myocardial segments were used as controls (n=19). Compared to control myocardium, levels of cAMP (3'-5'cyclic adenosine monophosphate, in fmol/mg wet weight, means+/-S.E.M.) were higher in hibernating (673+/-76 versus 518+/-47, P<0.05) but unchanged in stunned myocardium (513+/-73 versus 466+/-97, P>0.05). Protein expression of phospholamban, sarcoendoplasmic Ca(2+)-ATPase 2a, calsequestrin, the inhibitory subunit of troponin, as well as the activation of p38 MAP kinase were not different when compared to controls. However, heat shock protein 72 (Hsp72) was increased 55% in stunned (2.89+/-0.58 versus 1.86+/-0.32, P<0.05) but not in hibernating myocardium (1.68+/-0.34 versus 1.67+/-0.29, P>0.05).

Conclusions: The data from the present study suggest different pathophysiological mechanisms for myocardial hibernation and stunning. Alterations in the homeostasis of cAMP might be a compensatory mechanism in myocardial hibernation, whereas expression of Hsp72 appears to be cardioprotective in human myocardial stunning. Future studies should further elucidate these mechanisms and their potential impact on future therapeutic interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Calcium / metabolism
  • Coronary Artery Bypass
  • Coronary Circulation
  • Cyclic AMP / metabolism
  • Female
  • HSP72 Heat-Shock Proteins
  • Heat-Shock Proteins / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism
  • Myocardial Contraction
  • Myocardial Ischemia
  • Myocardial Stunning / diagnostic imaging
  • Myocardial Stunning / metabolism*
  • Myocardial Stunning / physiopathology
  • Myocardium / metabolism
  • Signal Transduction
  • Tomography, Emission-Computed
  • Tomography, Emission-Computed, Single-Photon
  • p38 Mitogen-Activated Protein Kinases


  • HSP72 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Cyclic AMP
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Calcium