Resting myocardial flow in hibernating myocardium: validating animal models of human pathophysiology

CHRONIC REVERSIBLE CONTRACTILE DYSFUNCTION is frequently identified in the evaluation of patients with coronary artery disease. There is intense clini cal interest in this area because it impacts directly on clinical decision making, and it has been the subject of several recent reviews (6, 23, 25, 4 6, 48). Nevertheless, until recently, basic understanding of physiological mechanisms has lagged far behind clinical descriptions because of the lack of appropriate animal models of the human disease. This contrasts with myoc ardial stunning (i.e., the transient dysfunction observed despite normal re sting perfusion following acute ischemia), where data from animal models pr eceded clinical studies demonstrating its importance in humans (2). A parti cular controversy at present relates to whether chronic contractile dysfunc tion simply reflects repetitive stunning or whether the heart has the intri nsic capability to alter its phenotype in response to repetitive episodes o f ischemia in a way that reduces its vulnerability to ischemia and results in "hibernating myocardium." At the center of the current controversy is wh ether resting myocardial perfusion in viable dysfunctional myocardium is no rmal or reduced. Available clinical studies summarizing quantitative measur ements of perfusion in patients and direct measurements in several recently developed chronic animal models of viable chronically dysfunctional myocar dium are discussed below.