Ischemia/reperfusion injury (myocardial stunning) may be mediated by oxygen derived-free radicals. Sodium nitroprusside (SNP), NO-donor, is known to reduce superoxide concentrations in isolated vascular tissue. To explore the efficacy of SNP on myocardial reperfusion injury, 23 halothane-anesthetized dogs underwent 15 minutes of left anterior descending coronary ary (LAD) occlusion and 3 hours of reperfusion. Animals were randomly assigned to receive either saline (n=11) or SNP infusion (n= 10, 10 ug/kg/min) through intracoronary catheter (24G) for 60 minutes beginning 15 minutes before LAD occlusion. Time course of recovery of regional myocardial function (calculated as Mw, slope of the preload recruitable stroke work curve,% SS, percent systolic shortening ; IMP, peak systolic intramyocardial tissue pressure; RSW, regional stroke work) and LAD coronary blood flow (CBF) as well as global myocardial functions were determined in SNP-treated and control groups. The results are as follows; 1) LAD occlusion produced a significant reduction (p<0.01) in Mw, % SS, IMP, and RSW in both the saline and SNP groups without significant differences between two groups except IMP. 2) Mw and IMP recovered to the baseline value by 15 and 60 min of reperfusion in the SNP group, whereas 120 and 180 min in the saline group, respectively. 3) At 3 hrs of reperfusion, % SS were 20% and 56% of the baseline values in the saline and SNP groups, respectively. The degree of recovery in % SS in the SNP group was greater than that in the saline group during early reperfusion. 4) CBF was higher in the SNP group as compared with the saline group throughout the reperfusion period. 5) Global myocardial function showed no significant differences between the two groups except a lower mean arterial pressure during SNP infusion in the SNP group. These findings suggest that intracoronary adminstration of SNP significantly attenuates regional regional myocardial dysfunction associated with transient episodes of ischemia. The protective mechanism of SNP may be related to attenuation of endothelial dysfunction and to decreased consumption during coronary occlusion.