Mikihiko Yokoyama

Acid Hydrolases in the Initiation of Ischemic Myocardial Necrosis

Alterations in myocardial acid hydrolases in acute ischemia were studied in relation to the evolution of cardiac cellular necrosis by the determination of cathepsin D, acid phosphatase (AcPase), and beta-glucuronidase activities of the myocardial fractions and by electron microscopic cytochemical studies on AcPase in the canine heart. In the normal myocardium, the same level of activity of acid hydrolases was found in sarcoplasmic reticulum (SR) as in the lysosome fraction. In electron microscopy, AcPase reaction products were observed markedly in SR and moderately in lysosomes, in residual bodies, and in Golgi apparatus. In the ischemic myocardium, at 20 to 30 min after coronary ligation, activation of these enzymes was observed in both SR and lysosomes, and at 60 to 90 min they were decreased in the particles and, in turn, increased in the cytoplasm accompanying the ischemic fine structural changes. At 2 to 3 hr those acid hydrolase activities in the cytosol were decreased, indicating the loss of enzymes from necrotic myocardial cells. Acid hydrolases are the most important factor for the evolution of ischemic myocardial necrosis by being activated not only in lysosomes but also in SR and by being released to the cytoplasm to disintegrate the cellular structures.