KATP channels are regulators of programmed cell death and targets for creation of novel drugs against ischemia/reperfusion cardiac injury.

The use of percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is associated with mortality rate of 5-7%. It is clear that there is an urgent need to develop new drugs that can effectively prevent cardiac reperfusion injury. ATP-sensitive K + (K ATP ) channel openers (KCOs) can be classified as such drugs. KCOs prevent irreversible ischemia and reperfusion injury of the heart. K ATP channel opening promotes inhibition of apoptosis, necroptosis, pyroptosis and stimulation of autophagy. KCOs prevent the development of cardiac adverse remodeling and improve cardiac contractility during reperfusion. KCOs exhibit antiarrhythmic properties and prevent the appearance of the no-reflow phenomenon in animals with coronary artery occlusion and reperfusion. Diabetes mellitus and a cholesterol-enriched diet abolish the cardioprotective effect of KCOs. Nicorandil, a KCO, attenuate major adverse cardiovascular event and the no-reflow phenomenon, reduces infarct size, decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction. The cardioprotective effect of KCOs is mediated by opening of mitochondrial K ATP (mitoK ATP ) and sarcolemmal K ATP (sarcK ATP ) channels, triggered free radicals' production, and kinases activation.