Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease

Abstract

OBJECTIVESThis study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a Katpchannel opening effect, during a percutaneous transluminal coronary angioplasty (PTCA) model in humans.BACKGROUNDThe ischemic PC effect is induced in 180 s ischemia, but not in 120 s ischemia in rabbit hearts. However, the duration of ischemia that induces PC effect and the role of the Katpchannel in the PC effect in humans are still unclear.METHODSForty-six patients with stable angina were randomly allocated to four groups: the duration of the first inflation as PC ischemia was 60 s in the PC60 group (n = 12), and 180 s in the PC180 group (n = 12). In the other groups, NC (80 μg/kg) was intravenously given for 1 min in the NC group (n = 12), and isosorbide dinitrate (ISDN) (40 μg/kg) was given in the ISDN group (n = 10). Five minutes after first inflation or drug administration, a second inflation was conducted for 120 s in each group. In the ECG, the lead with the largest shift in ST segment (deltaST max), and the sum of elevated ST levels in all leads (sigmaST) were determined.RESULTSIn the PC60 group, no significant difference was observed in either deltaST max or sigmaST between the first and second inflation. However, the second inflation in the PC180 group showed significantly lower levels of deltaST max and sigmaST compared with those of the first inflation. In the NC group, both deltaST max and sigmaST measured at 30 s and 60 s after balloon inflation were significantly lower than those of the first inflation in the PC60 and PC180 control groups. In the ISDN group, no significant difference was observed in deltaST max or sigmaST.CONCLUSIONIn human PTCA models, a PC effect is observed in 180 s ischemia, but not in 60 s ischemia. A pharmacological PC effect is induced by NC, a Katpchannel opener with a nitrate-like effect but not ISDN. This suggests that the opening of Katpchannels plays an important role in the protecting effect of NC.