Preliminary study on the protective effect of electroacupuncture Neiguan acupoint pretreatment on rats with myocardial ischemia-reperfusion injury:role of the miR-214-3p/NCX1 axis

Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.

Mechanism of the protective effects of noninvasive limbs preconditioning on myocardial ischemia-reperfusion injury

Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning （IPC）.Methods Forty Wistar rats were randomly divided into four experimental groups. In Group I , the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group I. In Group PL-N and Group PL-,, we administered L-nitro-arginine methyl ester （L-NAME） 10 mg/kg or hexamethonium chloride 20 mg,/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was determined by triphenyhetrazolium chloride staining.Results There were no statistically significant differences in mean arterial pressure and heart rate among these groups at any time point during the experiment （ P〉0. 05 ）. The myocardial infarct size （IS） was decreased significantly in Group PL and Group PL-U compared with Group I , and the IS/AAR was 34. 5%± 7.6%, 35.9%±8.6% and58.5%±8.5%, respectively （P〈0.05）. The IS/AAR was 49.1%±6.5% in Group PEN, and there was no significant difference compared with Group I （P〉0. 05 ）.Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important role in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.

Cardio-Protective Effects of Oral Nicorandil in Patients Undergoing Cardiac Valve Surgery

Background: Reduction of myocardial reperfusion injury during cardiopulmonary bypass is an essential requirement for increasing the success rate, decreasing morbidity and mortality of open-heart surgery. Aim: To study the role of pre-operative oral nicorandil in decreasing reperfusion cardiac injury in patients subjected to cardiac valve surgery. Patients and Methods: The study included 62 patients, who were equally randomized into two groups: nicorandil group and control group. Pre-operative, intra-operative and post- operative data were reported and analyzed. Left Ventricle Ejection Fraction (LVEF) was estimated pre-operatively and postoperatively for both groups. Troponin I, creatine kinase-muscle/brain (CK-MB), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured before surgery by 24 hours then 4, 12 and 48 hours after aortic cross clamp removal. Results: Nicorandil considerably decreased TNF-α and IL-6 after 4 and 12 hours following the removal of aortic clamping. It also reduced troponin-I and CKMB at the same time points. However, there were no important changes in IL-6, TNF-α, troponin-I and CK-MB levels in control group in comparison to nicorandil group in the next 48 hours following the removal of aortic clamping. Conclusions: Pre-operative oral nicorandil expressively decreased myocardial reperfusion damage during open heart valve operations, this evidenced by the decrease in the postoperative use of inotropic drugs, considerable reduction of postoperative elevation of cardiac enzymes and inflammatory cytokines with no reported complications.