The effect of NCO-700 (1), a protease inhibitor, on subcellular distribution of lysosomal enzymes was studied in the ischemic perfused rat heart. Ischemia was induced by lowering the afterload pressure of the working heart preparation. The subcellular distribution of lysosomal enzymes was estimated by the ratio of the activities of cathepsin D, beta,N-acetylglucosaminidase, and acid phosphatase in the cytoplasm to the total enzyme activities. Ischemia caused subcellular redistribution of lysosomal enzymes from the lysosomes to the cytoplasm, indicating the rupture of lysosomes. Compound 1 (1.75 x 10(-4) M) was provided for the heart 5 min before the onset of ischemia. Compound 1 appeared to inhibit the rupture of lysosomes being caused by ischemia. The mechanism by which 1 protects the myocardium against ischemic injury may involve the inhibition of lysosomal rupture in the ischemic myocardium.
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