A protease inhibitor, NCO-700, improves the contractile function in stunned canine myocardium

To explore the role of calcium-dependent protease in the stunned myocardium, open-chest dogs underwent 15 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. Dogs received a single bolus intravenous injection of either the protease inhibitor NCO-700 (n = 6) or saline (n = 6) 1 min before reperfusion followed by a 30-min infusion at the same dose. Regional myocardial function was assessed in terms of systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesis during occlusion. After reperfusion, recovery of contractile function, expressed as a percentage of the baseline value, was significantly greater in NCO-700-treated dogs as than in control dogs: -14.3 +/- 10.6 vs -48.9 +/- 7.2 (p < 0.05) at 15 min, 10.8 +/- 10.3 vs -31.1 +/- 9.0 (p < 0.05) at 30 min, 42.5 +/- 10.1 vs -16.4 +/- 9.1 (p < 0.005) at 1 h, and 47.5 +/- 8.3 vs -14.9 +/- 9.4 (p < 0.001) at 2 h. The data suggest that the protease inhibitor markedly improved contractile function in stunned myocardium by inhibiting intracellular protease activity.