The biology of myocardial hibernation.
Patients with chronic coronary artery disease frequently have contractile dysfunction that recovers upon reperfusion. The concept of myocardial hibernation views the observed reduction in contractile function not as the result of an ongoing energetic deficit, but as an adaptive down-regulation that serves to maintain myocardial integrity and viability. In the experiment, sustained perfusion-contraction matching, recovery of energy and substrate metabolism during ongoing ischemia, the potential for recruitment of inotropic reserve, lack of necrosis, and therefore recovery of function upon reperfusion are established features of hibernation. Apart from reduced calcium responsiveness, the underlying mechanisms are still unclear. In patients, the importance of reduced baseline blood flow vs. that of superimposed repetitive stunning is somewhat controversial; however, in most studies blood flow is reduced, and the myocardium must be ischemic often enough to have persistent dysfunction. Morphologically, hibernating myocardium displays features of dedifferentiation, with loss of cardiomyocytes and myofibrils, and of degeneration, with increased interstitial fibrosis. Patients with hibernating myocardium must be identified and undergo revascularization. With a better understanding of the underlying mechanisms of hibernation, these adaptive responses to ischemia can potentially be recruited and reinforced pharmacologically to delay impending myocardial infarction.
Heusch
G
G
Department of Pathophysiology, Center of Internal Medicine, University School of Medicine, Essen, Germany. gerd.heusch@uni-essen.de
Schulz
R
R
D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000378:metabolism / Q000503:physiopathology*
D002118:Calcium