Lessons from experimental models of hibernating myocardium

Abstract

Chronic animal models of viable dysfunctional myocardium are now available that recapitulate most if not all of the physiological findings in humans with hibernating myocardium. These include chronic reductions in resting perfusion and contractile function, critical limitations in coronary flow reserve and increased uptake of 18F-2-deoxyglucose. These changes occur in the absence of infarction or necrosis and are accompanied by regional reductions in sarcoplasmic reticulum calcium-handling proteins and myocyte loss that arise secondary to apoptosis. Longitudinal studies of viable dysfunctional myocardium indicate that a state of chronic stunning with normal resting flow precedes the development of hibernating myocardium but these are distinct entities within a continuum of chronic adaptations to ischemia. This indicates that reductions in resting flow are the result rather than cause of chronic contractile dysfunction. Thus, the original concept proposing an acute prolonged reduction in flow as the initial stimulus producing hibernating myocardium needs to be revised.