Inhibition with NCO-700, a protease inhibitor, of degradation of cardiac myofibrillar proteins during ischemia in dogs

NCO-700 is a newly synthesized inhibitor of both Cathepsin B and calcium-activated neutral protease. We examined whether NCO-700 inhibits degradation of myofibrillar proteins induced by cardiac ischemia in dogs anesthetized with pentobarbital. Cardiac ischemia was produced by complete occlusion of the left anterior descending coronary artery (LAD) for 3 or 6 hr. Myofibrils were prepared from the ischemic myocardium, in which LAD was occluded, and from the nonischemic myocardium, in which LAD was not occluded. Electrophoresis of myofibrils prepared from the ischemic myocardium revealed that there were many degradation bands of myofibrillar proteins as well as the bands corresponding to alpha-actinin (AN), the 55 kDa protein (55 K), actin (A), tropomyosin (TM), troponin I (TN I), Myosin light chain 1 (LC1) and Myosin light chain 2 (LC2). In addition, the content of AN, 55 K, A, TM, TN I, LC1 and LC2 in the ischemic myofibrils was lower than that in the nonischemic myofibrils. Treatment with NCO-700 at the total dose of 20 mg/kg, which was injected intravenously before and during ischemia, inhibited both appearance of the degradation bands and the decrease in the content of A, TM, TN I, LC1 and LC2 being produced by cardiac ischemia. NCO-700, however, did not inhibit the decrease in the content of 55K and AN being induced by ischemia.