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Intracellular Ca2+↑ Ca2+ Ca2+ overload Mitochondrial dysfunction →ATP production↓ Induction of apoptosis Impact of Myocardial Ischemia on Mitochondrial Function Impact of Opening Mt KATP Channel on IP K+ K+ K+ Nicorandil ( Mt KATP channel opener) ↓ Opening of Mt KATP Channel Depolarization of Mt membrane Ca2+ Reduce Ca2+ load Maintain Mt function Nicorandil, a Potent Cardioprotective Agents, Acts by Opening Mitochondrial KATP Channels 0 10 20 30 40 50 Control Nicorandil Nicorandil + 5HD Nicorandil + HMR1098 Cell Killed (%) * * *p0.05 vs Control Relative potency of nicorandil in opening surface KATP and mitochondrial KATP channels 5-HD: 5-hydroxydecanoate, mitochondrial KATP channel selective blocker HMR1098: sarcolemmal KATP channel selective blocker Cardioprotective effects of nicorandil Sato T et al. J Am Coll Cardiol, 2000; 35: 514 A Pharmacological preconditioning effect is induced by nicorandil Matsubara T et al. J Am Coll Cardiol 2000; 35: 345 PC60（n=12） PC180（n=12） Nicorandil（n=12） ISDN（n=10） 60sec Ischemic preconditioning Pharmacological preconditioning 120sec 180sec 120sec 1st inflation 2nd inflation 120sec 120sec 80μg/kg/min 40μg/kg/min 5min 5min 5min 5min 0 0.1 0.2 0.3 0.4 0.5 0.6 Control PC60 PC180 Nicorandil ISDN 0 0.1 0.2 0.3 0.4 0.5 0.6 Control PC60 PC180 Nicorandil ISDN Max ST elevation (After 30sec) Max ST elevation (After 60sec) (mV) (mV) p0.05 p0.05 p0.05 p0.05 Matsubara T et al. J Am Coll Cardiol 2000; 35: 345 A Pharmacological preconditioning effect is induced by nicorandil ?Clinical evidence in EU— IONA Study ?Clinical evidence in Japan— JCAD Study Clinical Evidence Clinical Application of Pharmacological Preconditioning (PC) Ischemic PC such as pre-infarction angina improves long-term mortality in patients with reperfused AMI It is impossible to induce anginal attacks before the onset of AMI Is it possible to protect myocardium from lethal ischemia and improve long-term mortality by pharmacological PC? IONA (Impact Of Nicorandil in An