Pre-treatment of a single high-dose of atorvastatin provided cardioprotection in different ischaemia/reperfusion models via activating mitochondrial KATP channel

A number of clinical trials have shown that a high loading dose of atorvastatin (Ator) within 24 h before percutaneous coronary intervention (PCI) exerts protective effects on the cardiovascular system. However, the potential mechanisms regarding this rapid benefit of Ator remain elusive. Our study introduced three different ischaemia/reperfusion (I/R) models: I/R in vivo, I/R in vitro and oxygen–glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes to observe the protective effect of a single loading dose of Ator pre-treatment and further to explore the potential mechanisms of this protective effect with confocal laser scanning microscopy, flow cytometry, biochemical and morphology methods. We found that the pre-treatment of high-dose Ator decreased the cardiac injury and maintained the integrity of mitochondria in all three of the I/R models, which was similar to ischaemic pre-conditioning (IPC). We used the mitochondrial KATP channels (mitoKATP channels) inhibitor 5-hydroxydecanoate (5-HD) and the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) to analyse the underlying mechanisms. The results showed that the pre-treatment of Ator significantly decreased I/R-induced injury, and maintained the functional integrity of mitochondria through alleviating Ca2+ overload, reactive oxygen species burst, inhibiting the opening of mPTP and preventing mitochondrial membrane potential (ΔΨm) depolarisation. The present results demonstrated that a single dose of Ator might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening through activating the mitoKATP channels. This result may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury.