Nicorandil reduces myocardial infarct size by opening the KATP channel in rabbits

We examined whether nicorandil reduces myocardial infarct size (1) when administered before ischemia, and (2) when administered before reperfusion, and whether (3) infarct size is influenced by the plasma nicorandil concentration and the opening of the KATP channel. Anesthetized open-chest Japanese white male rabbits were subjected to a 30 min coronary occlusion (ischemia) and a 48 h reperfusion in the following six groups; Group 1 (n=9): control group, Group 2 (n=9): pre-ischemia to post-reperfusion group (nicorandil 10 mu g/kg/min, i.v.), Group 3 (n=7): pre-ischemia to post-reperfusion+glibenclamide group (glibenclamide 0.3 mu g/kg, i.v.+micorandil 10 mu g/kg/min, i.v.), Group 4 (n=8): pre-reperfusion to post-reperfusion group (nicorandil 10 mu g/kg/min, i.v.), Group 5 (n=8): pre-ischemia low-dose group (nicorandil 10 mu g/kg/min for 5 min i.v.), Group 6 (n=7): pre-ischemia high-dose group (nicorandil 100 mu g/kg/min for 5 min i.v.). The plasma nicorandil concentrations were measured from blood samples taken immediately before the ischemia. After the 48 h reperfusion, the size of the infarct was measured histologically with immunohistochemical actin staining and expressed as a percentage of the area at risk. Results: Infarct sizes were as follows; Group 1 (control): 41.0+/-3.5%, Group 2: 31.3+/-2.0% (P<0.05 vs. control), Group 3: 40.9+/-3.4%, Group 4: 45.2+/-4.4%, Group 5: 35.8+/-3.3%, Group 6: 25.2+/-3.9% (P<0.05 vs. control). Infarct size was inversely correlated with the plasma nicorandil concentrations (y=-0.031x+41.0, r=0.65, P<0.05). Conclusions: The pre-ischemic but not post-ischemic administration of nicorandil reduced the size of myocardial infarct by opening the KATP channels, and this effect was dependent on the plasma nicorandil concentrations immediately before the ischemia induced in rabbits. (C) 1997 Elsevier Science Ireland Ltd.