Myocardial hibernation--adaptation to ischemia

The concept of myocardial hibernation implies a downregulation of contractile function as an adaptation to a reduction in myocardial blood flow that serves to maintain myocardial integrity and viability during persistent ischemia. Unequivocal evidence for this concept exists in scenarios of myocardial ischemia that last for several hours; the recovery of energy and substrate metabolism, the potential for recruitment of inotropic reserve at the expense of metabolic recovery, and lack of necrosis are established criteria of short-term hibernation. Furthermore, experimental studies have demonstrated regional myocardial dysfunction at reduced resting blood flow that recovered upon reperfusion, which is consistent with chronic hibernation. 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. The mechanisms of short-term hibernation, apart from reduced calcium responsiveness, are not clear at present. With the identification of the underlying mechanism(s) of hibernation, it can potentially be recruited and reinforced pharmacologically to delay impending myocardial infarction.