Acute atorvastatin treatment restores the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats

// Tao Sun 1 , Hong-Ju Zhang 2 , Chayakrit Krittanawong 3 , Su Wang 1 , Ying Tao 1 , Zhao Li 1 , Qiancheng Yin 1 , Donghua Zhang 1 , Qian Wang 1 , Ji Huang 1 , Jingmei Zhang 1 , Zhizhong Li 1 and Yutong Cheng 1 1 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 2 Division of Ultrasound, Fu Wai Hospital, National Center for Cardiovascular Diseases, Beijing, China 3 Department of Internal Medicine, Icahn School of Medicine at Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA Correspondence to: Yutong Cheng, email: stzhjszcn@163.com Keywords: ischemic postconditioning, statin, atorvastatin, hyperlipidemia, infarct size-limiting effect Received: November 24, 2016      Accepted: June 16, 2017      Published: July 14, 2017 ABSTRACT Background: Ischemic Postconditioning (IPC) reduces ischemia/reperfusion (I/R) injury under normal conditions. HMG-CoA reductase inhibitors (statins), which inhibit the synthesis of mevalonate, can interfere with the cardioprotective effect of IPC. However, the beneficial role of IPC in hyperlipidemic patients, post-acute administration of statins remains unknown. This study was to determine if acute administration of atorvastatin affect the infarct size-limiting effect of IPC in hyperlipidemic rats. Results: Compared to control group, infarct size decreased more significantly in atorvastatin+IPC and atorvastatin+IPC+wortmannin groups than IPC or atorvastatin+IPC+PD98059 groups. Phosphorylation of PI3K/Akt was attenuated in atorvastatin + IPC+ wortmannin group, phosphorylation of P42 MAPK/ERK was increased in atorvastatin+IPC and atorvastatin+IPC+wortmannin groups. Materials and Methods: Ninety four-weeks old male SD rats fed with cholesterol enriched diet for six weeks were randomized into nine groups ( n = 10/group) - sham group, control group, IPC group, atorvastatin group, wortmannin group, PD98059 group, atorvastatin+IPC group, atorvastatin+IPC+wortmannin group and atorvastatin+IPC+PD98059 group. Atorvastatin was administered orally 12 hours before myocardial reperfusion. Conclusions: Post-translational activation of P42 MAPK/ERK, rather than PI3K/Akt, participates in the net protective effect of IPC and atorvastatin in hyperlipidemia.