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

Abstract

Background: The use of percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is associated with a 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.

Results: 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 in 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, attenuates major adverse cardiovascular event and the no-reflow phenomenon, reduces infarct size, and decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction.

Conclusion: The cardioprotective effect of KCOs is mediated by the opening of mitochondrial K_ATP (mitoK_ATP ) and sarcolemmal K_ATP (sarcK_ATP ) channels, triggered free radicals' production, and kinase activation.

Keywords: KATP channels; cardiac remodeling; heart; microvascular obstruction; programmed cell death; reperfusion.