Heterogeneity of metabolic parameters in the left ventricular myocardium and its relation to local blood flow

It is well established that myocardial blood flow is heterogeneous on the l ocal level. During recent years comprehensive studies have been undertaken to assess the relation between myocardial metabolism and spatial blood flow heterogeneity. Based on the type of measurements two major groups of studi es have been performed: enzyme activity and tissue metabolite level assessm ents. Enzyme activity measurements have provided only limited insight into the coupling of local metabolism and flow. This is probably due to the fact that, in addition to estimated V.. values, local substrate affinity (K-m v alues) and substrate concentrations affect the metabolite fluxes. However, the latter two variables remain normally unknown. In contrast, valuable ins ight has been obtained concerning flow-metabolism matching from tissue meta bolite measurements, especially when connected with mathematical model anal yses. The latter permitted the calculation of metabolic flux rates (e.g., p roduction of oxidation water, citric acid cycle flux, glucose uptake, fatty acid uptake) or the translation of the metabolic indexes into physiologica lly meaningful local metabolite concentrations (e.g., free cytosolic adenos ine). The bottom line of the studies reported to date is that the broad ran ge of myocardial flows observed under resting control conditions correlates with local metabolism possibly affected by spatial differences in adrenerg ic stimulation. Thus, high flow samples exhibit a higher oxidative metaboli sm than low flow samples. As a result the flow threshold below which local myocardial ischemia ensues is higher in control high flow samples. The impo rtance of these findings with respect to local flow-metabolism matching is underlined by the finding that the probability of developing an infarction following ischemia/reperfusion is related to the functional state of the my ocardium under control conditions, i.e., the local level of flow-metabolism matching.