ISCHEMIC INJURY OF MYOCARDIUM *

The sudden onset of ischemia in myocardium is followed within a few seconds by a series of striking functional changes: The area becomes cyanotic; cooler; hydrogen accumulates; electrocardiographic changes appear; and, within 30 to 60 seconds, contraction ceases in the affected myocardium. These changes within the ischemic focus are directly related to the development of local anoxia, which causes the affected cells to shift from an aerobic to an anaerobic form of metabolism, resulting in a substantial decrease in energy production. Although injured and nonfunctional, these severely ischemic, markedly anoxic cells are viable and survive for a period of time. Early restoration of the coronary blood flow to an ischemic focus is followed by almost instantaneous restoration of aerobic metabolism and contractile function. However, if the period of ischemia is more prolonged, restoration of the blood supply is not followed by restoration of function, since the affected cells are either dying or dead. The severely ischemic viable cells are reversibly injured, whereas the severely ischemic dead cells are irreversibly injured. Our chief interest has been in determining what event or series of events within the cells dictates the onset of irreversible injury.' Our studies are predicated on the assumption that intracellular events discoverable by direct analysis of the tissue lead to the development of the irreversible state. Tissue known to be severely ischemic and fairly uniformly injured is required for analysis in direct studies of early changes in structure and/or function during ischemic injury. One must be able to identify and sample the affected tissue even though it appears normal upon gross examination. We have found that the posterior papillary muscle is an area of maximum ischemia in the large posterolateral infarct resulting from high occlusion of the circumflex branch of the left coronary artery in the dog heart.2 The posterior papillary muscle is easily identified, and the upper two-thirds of the muscle are uniformly injured in those dogs in which the cyanosis extends to the apex of the heart posteriorly. The muscle is ultimately almost completely replaced by scar tissue. The anterior superior portion of the septum of the left ventricle is not involved in this infarct; therefore it is used as a source of nonischemic control tissue.