Effects of High Potassium Cardioplegia and ATP-Sensitive Potassium Channel Openers on Endothelial Cells Against Ischemia-Reperfusion Injury

Background: The roles of hyperkalemic cardioplegia (CPG) and endothelial ATP-sensitive potassium (KATP) channels in endothelial protection against ischemia-reperfusion injury (IRI) during cardiac surgery remain unclear. Objectives: This study aimed to investigate the impacts of KATP channel openers (KCOs) on endothelial cell viability and nitric oxide (NO) production under normal conditions and cardioplegia exposure after short and long reperfusion. Methods: Human endothelial cells (EA.hy926) were subjected to ischemia-reperfusion (IR), with or without the KCOs, including pinacidil, diazoxide, nicorandil, and ZD0947. The effects of nicorandil and ZD0947 were also evaluated in conjunction with cardioplegia. The KCOs preserved endothelial cell viability against IRI under standard conditions at both time points. Results: Ischemia-reperfusion significantly reduced NO production at 24 hours, while ZD0947 maintained early NO levels and improved NO production at 24 hours, comparable to nicorandil. Cardioplegia alone did not affect cell viability or NO production; however, its application under IR conditions was more detrimental than IR alone. Notably, nicorandil and ZD0947 preserved cell viability in this context. Nitric oxide levels at 30 minutes remained at basal levels in the cardioplegia, IR, and cardioplegia with IR groups. However, treatment with nicorandil and ZD0947 in the cardioplegia with IR condition significantly increased NO levels compared to the control. Conclusions: ZD0947 and nicorandil effectively mitigated endothelial cell damage in response to IR with cardioplegia.