Slowly activating voltage-gated potassium current potentiation by ML277 is a novel cardioprotective intervention

Cardiovascular disease is thought to account for nearly a third of deaths worldwide, with ischemic heart disease, including acute coronary syndromes such as myocardial infarction, accounting for 1.7 million deaths per year. There is a clear need for interventions to impart cardioprotection against ischemia. Here, we show that the slowly activating voltage-gated potassium current (IKs) potentiator ML277 imparts cardioprotection against ischemia in cellular and whole-heart models by modulating the action potential duration. In three different metabolic inhibition and reperfusion models, an increased contractile recovery and cell survival was observed with ML277, indicative of protection. Finally, ML277 reduced infarct size in an ex vivo Langendorff coronary ligation model, including if only applied on reperfusion. In conclusion, potentiation of the IKs with ML277 imparted a cardioprotection that was equivalent to the protection reported previously by ischemic preconditioning. These data suggest that IKs potentiation may be therapeutically useful in acute coronary syndromes.

Automated summary

Cardiovascular disease is a major cause of global deaths, with ischemic heart disease, including myocardial infarction, leading to 1.7 million deaths annually. The study demonstrates that ML277, a potassium current modulator, provides cardioprotection against ischemia by modifying action potential duration. In various models, ML277 improves contractile recovery, cell survival, and reduces infarct size, suggesting its therapeutic potential in acute coronary syndromes.