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 clinical 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, 46, 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 myocardial stunning (i.e., the transient dysfunction observed despite normal resting perfusion following acute ischemia), where data from animal models preceded clinical studies demonstrating its importance in humans (2). A particular controversy at present relates to whether chronic contractile dysfunction simply reflects repetitive stunning or whether the heart has the intrinsic capability to alter its phenotype in response to repetitive episodes of ischemia in a way that reduces its vulnerability to ischemia and results in "hibernating myocardium." At the center of the current controversy is whether resting myocardial perfusion in viable dysfunctional myocardium is normal or reduced. Available clinical studies summarizing quantitative measurements of perfusion in patients and direct measurements in several recently developed chronic animal models of viable chronically dysfunctional myocardium are discussed below.