Myocardial "stunning" and substrate metabolism

Although many experts have dismissed myocardial substrate metabolism as having a role in the phenomenon known as "myocardial stunning," recent studies using the isolated perfused working rat heart (especially from Lopaschuk's laboratory) have provided evidence that perhaps there is a role for alterations in myocardial substrate metabolism in producing and improving myocardial stunning. Moderate concentrations of glucose (11 mM) have proved to provide maximal recovery from hypothermic cardioplegic arrest. Furthermore, one mechanism of the protective effect of adenosine after low flow cardiac ischemia appears to be stimulation of glucose metabolism and inhibition of glycolysis. Other manipulations of metabolism that result in the same effect include: stimulation of pyruvate dehydrogenases by dichloroacetate; and prevention of fatty acid inhibition of glucose oxidation by I-carnitine palmitoyltransferase I. All of these interventions enhance glucose oxidation without increasing or actually decreasing glycolysis. The mechanism for the improvement in functional recovery is still hypothetical. In addition, these effects are seen only in the presence of high fatty acid concentrations and the experiments have been in isolated perfused rat hearts.