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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 high-lighted by high-spatial-resolution imaging techniques. stunned myocardium; hibernating myocardium; inotropic reserve; cardiac imaging; myocardial wall stress; ventricular remodeling

Tagged MRI and PET in severe CAD: discrepancy between preoperative inotropic reserve and intramyocardial functional outcome after revascularization. Am J Physiol Heart Circ Physiol 287: H2226-H2233, 2004. First published July 1, 2004; doi:10.1152/ajpheart.00263. 2004.--In severe coronary artery disease (CAD), it has been shown that intramyocardial inotropic reserve as assessed with tagged magnetic resonance imaging (MRI) is uniformly distributed among positron emission tomography (PET) patterns reflecting normal or concomitant reductions in perfusion and glucose metabolism. This preliminary study aimed to delineate the relationship between preoperative values of intramyocardial inotropic reserve (in different PET patterns of perfusion and glucose uptake) and intramyocardial functional outcome after surgical revascularization in severe CAD. Twelve patients underwent preoperative tagged MRI (baseline, 10 [micro]g*[kg.sup.-1]*[min.sup.-1] of dobutamine), [H.sub.2][sup.15]O/[[sup.18]F]fluorodeoxyglucose PET imaging, and postoperative resting tagged MRI. Regional midmyocardial circumferential shortening ([E.sub.cc], in %) and PET patterns (normal, match viable, mismatch viable, and infarcted) were assessed in three tagged MRI/PET short-axis slices. [E.sub.cc] at baseline ranged from 12 [+ or -] 6 to 8 [+ or -] 5 and 4 [+ or -] 4% in normal, match-viable, and infarcted regions, respectively (P < 0.05) and was 8 [+ or -] 5% in mismatch-viable regions. Of the 429 regions studied, 187 showed preoperative inotropic reserve with dobutamine, but 238 showed postoperative functional improvement. Postoperative functional improvement was less common in infarcted regions (41 vs. ~60% in the other PET patterns), but the extent of improvement was similar among PET patterns (~6%). Postoperative functional improvement occurred in 53% of all (normal, match viable, and mismatch viable) regions without inotropic reserve. In severe CAD, revascularization affords greater intramyocardial functional benefit than expected from the evaluation of intramyocardial inotropic reserve with low-dose dobutamine. Postoperative functional improvement in PET-viable regions without inotropic reserve suggests that factors other than regionally enhanced perfusion contribute to such functional improvement. magnetic resonance imaging; positron emission tomography; dobutamine; myocardial viability

Thyroid hormones are involved in the regulation of many physiological processes and regulate gene transcription by binding to their nuclear receptors TR[alpha] and TR[beta]. In the absence of triiodothyronine (T3), the unliganded receptors (aporeceptors) do bind DNA and repress the transcription of target genes. The role of thyroid hormone aporeceptors as repressors was observed in hypothyroid adult mice, but its physiological relevance in nonpathological hypothyroid conditions remained to be determined. Here we show that, in the normal mouse fetus, TR[alpha] aporeceptors repress heart rate as well as the expression of TR[beta] and several genes encoding ion channels involved in cardiac contractile activity. Right after birth, when T3 concentration sharply increases, liganded TR[alpha] (holoreceptors) turn on the expression of some of these same genes concomitantly with heart rate increase. These data describe a physiological situation under which conversion of TR[alpha] from apo-receptors into holo-receptors, upon changes in T3 availability, plays a determinant role in a developmental process.

The impact of blood flow reductions on the intramyocardial inotropic reserve has not yet been established in coronary artery disease (CAD). We therefore evaluated in severe CAD the relationship between positron emission tomography (PET) patterns of perfusion and glucose uptake and the corresponding tagged magnetic resonance imaging (tagged MRI) values of midmyocardial strains under low-dose dobutamine. Eighteen patients underwent tagged MRI (at rest, with dobutamine) and [H.sub.2][sup.15]0/[sup.18]F fluorodeoxyglucose PET. Regional midmyocardial circumferential shortening ([E.sub.cc]) and PET patterns (normal, match viable, mismatch viable, and infarcted) were assessed in three tagged MRI/PET shortaxis slices. Regional [E.sub.cc] at rest correlated with both perfusion (r = 0.49) and glucose uptake (r = 0.58). The presence of the inotropic reserve was similar in normal, match viable, and infarcted (~40% of regions vs. 52% in mismatch viable, P < 0.05), but the extent of the increase after dobutamine was lower in infarcted regions (P = 0.06). Within each PET pattern, regions were grouped according to their [E.sup.cc] values at rest into three categories (high, intermediate, and low contractile performance). In mismatch viable (hibernation), the inotropic reserve was similar among the three categories, but in the other PET patterns the presence and extent of the inotropic reserve was higher in those regions with lowest [E.sub.cc] (without significant differences in perfusion). In severe CAD, the presence of the inotropic reserve assessed by midmyocardial changes under dobutamine does not relate to resting perfusion. At a similar level of perfusion, the presence of the inotropic reserve is inversely related to contractile performance at rest, but our results suggest that it may not be true for hibernating myocardium. tagged magnetic resonance imaging; positron emission tomography; myocardial perfusion; coronary artery disease

Positron emission tomography images revealed that patients with coronary artery disease show a greater increase in myocardial oxygen consumption (MVO2) than in myocardial perfusion during exposure to inotropic agents such as dobutamine. This perfusion-MVO2 mismatch leads to an increase in oxygen extraction from the myocardial tissue.

Experimental studies reveal the existence of an inverse relationship between the extent of ischemic injury and the rate of glycolysis and lactate production during ischemia. Increase of glycolysis by different methods decreases the damage during ischemia and improves the recovery of contractile function with reperfusion. Increasing the perfusate levels of glucose and/or insulin, stimulating glycolysis and modulating preischemic glycogen stores help manipulate glycolytic ATP production in isolated perfused rabbit hearts subjected to low-flow ischemia.

Experimental analyses of the effects of ischemic preconditioning in isolated rabbit heart reveal that ischemic preconditioning promotes anaerobic glycolytic ATP release using exogenous glucose and protects the myocardial structures. Preconditioning postpones the start of ischemic contracture, increases reperfusion effects and reduces ischemic injuries to the myocardium by increasing the ATP level. The delay in ischemic contracture helps improve functional recovery with reperfusion.

A study to investigate the mechanism by which adenosine and adenosine receptors protect the heart during ischemia-reperfusion is presented. The study protocol involved the constant perfusion of isolated rabbit hearts with 1 micromolar adenosine before inducing low-flow ischemia followed by reperfusion. The results indicate that adenosine protects the heart against ischemic injury via receptor-mediated stimulation of anaerobic glycolysis. On the other hand, its protective action during reperfusion is mediated by vasodilation.