[Transmural heterogeneity of the left ventricular wall: subendocardial layer and subepicardial layer]

The myocardium of the left ventricular wall is not homogeneous, but demonstrates transmural heterogeneity in myocardial blood flow, myocardial metabolism, and contraction and relaxation dynamics. Reimer and colleagues recognized that irreversible injury of the ischemic myocardium develops as a transmural wavefront, occurring first in the subendocardial myocardium, and with longer periods of ischemia, the wavefront of necrosis moves from the subendocardial zone across the wall to progressively involve more of the transmural thickness of the ventricular wall, ultimately becoming nearly transmural. This phenomenon was named the "wavefront phenomenon", and is the morphological counterpart of the transmural heterogeneity of the metabolism and blood flow. Autoregulation of myocardial blood flow is accomplished by changes in intramyocardial vascular resistance and intramyocardial pressure. It is more difficult to maintain the autoregulation in the subendocardial myocardium because contraction is greater, oxygen demand is greater, and myocardial pressure is higher in the subendocardium than in the subepicardial layer. In the normal myocardium, contraction is greater in the subendocardial layer, as is wall stress, accounting for the higher subendocardial energy requirements. Consistent with these findings, higher rates of metabolic activity and greater oxygen extraction are found in this region. As a consequence, ischemia becomes more severe and myocardial cells undergo necrosis first in the subendocardium. Under normal conditions, production and utilization of high-energy phosphates [adenosine triphosphate(ATP) and creatine phosphate] in the subendocardial myocardium are more active than in the subepicardial myocardium, but decline more easily in the subendocardium during ischemia, which induces the subendocardial ischemic injury. Lower production of Ca(2+)-ATPase in the subendocardium might also contribute to the subendocardial injury. Wavefront necrosis starts from the subendocardium, but the production of high-energy phosphates in the subepicardium is known to increase and compensate for the reduction in high-energy phosphate production in the subendocardium. Animal experiments have shown that systolic thickening of the endocardial half of the ventricular wall is double that in the epicardial half. Today, this can be confirmed in humans with the tissue Doppler tracking method which is completely noninvasive. Furthermore, the subepicardial half of the ventricular wall is known to compensate for the decreased systolic thickening of the subendocardial half in the case of subendocardial injury, which is called vertical compensation and is the mechanical counterpart of the concept of metabolic compensation. Many new technologies, including the tissue Doppler tracking method, magnetic resonance imaging tagging, and myocardial contrast echocardiography, will give more accurate information about the myocardial heterogeneity of layer-by-layer motion and blood flow, and will contribute to early detection and quantitative estimation of ischemia and other diseases of which the main lesion is in the subendocardium.