Spatial heterogeneity of myocardial perfusion and metabolism.
Left ventricular myocardium is characterized by a substantial spatial heterogeneity of both perfusion and metabolism. Under resting conditions, the transmural gradient of myocardial oxygen consumption (MVO2) from the subepi- to the subendocardial layer exceeds that of coronary flow, resulting in a lower subendocardial PO2, altered kinetics of oxidative phosphorylation, and enhanced free cytosolic adenosine. Within each layer, there is a major spatial variability of perfusion: Local flow rates in individual myocardial samples (200 mg) range from 20-250% of the mean myocardial blood flow. Low flow areas (< 50% of mean flow) display a rather low uptake of fatty acids and glucose; the uptake of these substrates increases in proportion to local flow. There is also a close relationship between local perfusion and the local turnover of the tricarboxylic acid cycle and, thus, MVO2 as was recently demonstrated using 13C NMR techniques. Consequently, within the well perfused left ventricular myocardium local MVO2 and, thus, energy turnover varies more than 3-fold between low and high flow areas. Low flow areas are not ischemic, since local lactate, adenosine, and ATP are comparable to mean flow areas. When coronary perfusion pressure is reduced, the transmural perfusion gradient reverses resulting in impaired energy status and enhanced adenosine predominantly in the subendocardium. This rise in local adenosine or lactate requires a decrease of the individual local flow by more than 50% of its preischemic value. It, thus, appears that not the absolute level of local flow predicts the impact of ischemia but its relative change.