[Pathophysiology of the "hibernating" myocardium]

Myocardial ischemia has traditionally been viewed as an imbalance between energy supply and demand. Within the first few seconds following an acute reduction of myocardial blood flow, energy demand of the hypoperfused myocardium clearly exceeds the reduced energy supply. However, this imbalance between energy supply and demand is an inherently unstable condition since ischemia induces mechanisms which are not yet understood, but reduce contractile function and thus energy demand. In the subsequent steady-state condition, the amount of contractile dysfunction is in proportion to the reduction of myocardial blood flow. A situation of persistent ischemic contractile dysfunction in viable myocardium which normalizes upon reperfusion has been termed myocardial hibernation. The metabolic status of such hibernating myocardium improves over the first few hours as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. The hibernating myocardium can respond to an inotropic stimulation by dobutamine with increased contractile function, however, at the expense of a renewed worsening of the metabolic status. This situation of an increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify hibernating myocardium. The development of such delicate balance between regional myocardial blood flow and function during early ischemia is disturbed by unfavorable alterations in supply and demand. When after 5 min of ischemia, at a blood flow reduction compatible with the development of myocardial hibernation over 90 min, energy supply is further reduced by a further reduction of myocardial blood flow, necroses develop. Likewise, increasing energy demand by continuous inotropic stimulation with dobutamine induces necroses. Thus, both the further reduction in energy supply by an increasing severity of ischemia and an enhanced energy expenditure by continuous inotropic stimulation impair the development of myocardial hibernation and precipitate myocardial infarction. Hibernation over the first few hours of ischemia (short-term hibernation) is well characterized in animal experiments. Increased release of endogenous adenosine and activation of ATP-dependent potassium channels as the underlying mechanisms have been ruled out. The existence of hibernation over weeks or months (long-term hibernation) can only be inferred from clinical studies. In long-term hibernating myocardium morphological alterations occur. In myocardial biopsies from patients with prolonged contractile dysfunction which was reversible after bypass surgery, myofibrils are reduced in number and disorganized. Myocardial glycogen content as well as the extracellular collagen network are increased. Thus, despite the fact that the myocardium remains viable during persistent ischemia and contractile dysfunction is reversible upon reperfusion, there are severe morphological alterations. Understandably, full functional recovery following reperfusion can therefore require weeks or even months.