LIMITATION OF MYOCARDIAL INFARCT SIZE BY NICORANDIL AFTER SUSTAINED ISCHEMIA IN PIGS

Nicorandil is a compound with hybrid properties of nitrates and adenos ine triphosphate (ATP)-sensitive potassium channel (K-ATP) opening. Th e effects of nicorandil and isosorbide dinitrate (ISDN) were investiga ted in a model of 60-min coronary occlusion/180-min reperfusion in ope n chest pigs. Three groups of 10 pigs were randomly assessed to receiv e saline or equihypotensive doses of nicorandil or ISDN. Drug infusion was started at 30 min of ischemia and continued throughout reperfusio n. Area at risk (AAR) and infarcted area (IA) were assessed by monastr al blue dye-triphenyltetrazolium dual staining technique and calculate d by planimetry. Myeloperoxidase concentration (MPO) in the nonischemi c area and in the IA was assessed as an index of presence of neutrophi ls. Measurements of reduced glutathione (GSH), oxidized glutathione (G SSG), lipofuscine, and malondialdehyde were performed on coronary vein blood as indexes of oxidative stress. IA, as a percentage of AAR, was 78 +/- 10% after saline, 61 +/- 12% after N (p < 0.05 vs. saline), an d 69 +/- 14% after ISDN (not significant vs. saline). Cardiac output a nd left ventricular dP/dt were depressed during coronary occlusion in all groups and their recovery during reperfusion was earlier in the mi crorandil group. In the saline group, MPO was increased in the IA comp ared to the nonischemic area (78 +/- 63 vs. 21 +/- 21 mu g/mg prot, p = 0.02). In the ISDN group and in the nicorandil group, the increase o f MPO concentration in the IA compared to the nonischemic area was not statistically significant (44 +/- 27 vs. 25 +/- 20 mu g/mg prot, p = 0.09 and 43 +/- 39 vs. 34 +/- 51 mu g/mg prot, p = 0.47, respectively) . No differences were observed on the indexes of oxidative stress amon g groups. Thus, nicorandil, administered after a prolonged period of c oronary occlusion, reduced IA and improved the recovery of hemodynamic s during the course of reperfusion compared to saline and ISDN. Nicora ndil and ISDN tended to reduce neutrophils infiltration in IA. The mec hanism of the protective effect of nicorandil is elusive and may be re lated to a direct activation of myocardial K-ATP channels and/or to th e antineutrophil activity.