Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning

Abstract

Croisille, Didier Revel, and Marc F. Janier. Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning. Am J Physiol Heart Circ Physiol 291: H2570 -H2582, 2006. First published July 21, 2006 doi:10.1152/ajpheart.01249.2005.-Patients with severe chronic coronary artery disease (CAD) exhibit a highly altered myocardial pattern of perfusion, metabolism, and mechanical performance. In this context, the diagnosis of stunning remains elusive not only because of methodological and logistic considerations, but also because of the pathophysiological characteristics of the myocardium of these patients. In addition, a number of alternative pathophysiological mechanisms may act by mimicking the functional manifestations usually attributed to stunning. The present review describes three mechanisms that could theoretically lead to reversible mechanical dysfunction in these patients: myocardial wall stress, the tethering effect, and myocardial expression and release of auto-and paracrine agents. Attention is focused on the role of these mechanisms in scintigraphically "normal" regions (i.e., regions usually showing normal perfusion, glucose metabolism, and cellular integrity as assessed by nuclear imaging techniques), in which stunning is usually considered, but these mechanisms could also operate throughout the viable myocardium. We hypothesize that reversion of these three mechanisms could partially explain the unexpected functional benefit after reperfusion recently highlighted by high-spatial-resolution imaging techniques. stunned myocardium; hibernating myocardium; inotropic reserve; cardiac imaging; myocardial wall stress; ventricular remodeling SUMMARY OF CLINICAL PROBLEMIN RECENT YEARS, WIDESPREAD utilization of noninvasive cardiac imaging methods has greatly improved the synergy between clinical and basic investigation of cardiac ischemic pathophysiology. Thus imaging methods have shown that the reversible left ventricular (LV) dysfunction arising from brief coronary occlusion and reflow (myocardial stunning), first described in animal models (80), occurs in humans. Two major hypotheses explain this phenomenon: 1) the oxyradical hypothesis, which proposes that oxidant stress impairs LV function (18), and 2) the calcium hypothesis, which postulates that stunning results from disturbed myocyte calcium homeostasis (98). On the other hand, the hibernating myocardium (136, 137) was first discovered by imaging methods in humans, and it was originally defined as "resting LV dysfunction due to reduced coronary blood flow that can be partially or completely reversed by myocardial revascularization and/or by reducing myocardial oxygen demand" (136). The concept was refined when ultrastructural investigations showed a distinctive morphology for hibernating myocardium, generally without necrosis, but with loss of sarcomeres and myofibrils (suggesting a "dedifferentiation" process toward an embryonic phenotype), with loss of mitochondria and increased glycogen storage (9,19,27,162)...

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