Spatial heterogeneity of myocardial circulation and energy metabolism

Abstract

Within the left ventricular myocardium, substantial differences can be observed in terms of both perfusion and energy turnover. In addition to the small transmural gradient from the subepi--to the subendocardium (1:1.2), more recent high-resolution studies reveal a major patchwork-pattern, e.g., in terms of flow. Adjacent 200 microliters areas can differ more than 3-fold in local perfusion. Low flow and high flow areas (< 50% or > 150% of mean flow, respectively) represent up to 1/5 of the left ventricular myocardium. This local flow pattern is temporally stable for at least days and possibly weeks. Low and high flow areas also differ in local energy metabolism. High flow areas are characterized by enhanced glucose phosphorylation and fatty acid permeability, resulting in increased uptake of these substrates. This is the basis for the recent finding that high flow areas are characterized by an enhanced turnover of the citric acid cycle and thus of local O2 consumption. Since local O2 supply and consumption are closely coupled, low flow areas display no biochemical signs of ischemia. Reducing local flow by 50% results in a similar rise of adenosine or lactate in low and high flow areas. Following complete cessation of perfusion, high flow areas display a greater risk of infarction, indicating enhanced energy demand. Further studies are needed to elucidate the molecular basis of this spatial heterogeneity and to test whether the 3-fold differences in local energy turnover within the myocardial wall also translate into comparable variations of local contractility.