| Myocardium ischemia/reperfusion (I/R) injury is a phenomenon often happened in clinical practice. Although ischemic preconditioning (IPC) and remote ischemic preconditioning (RPreC) can decrease the myocardial injury significantly, intensive research had shown that they were elicited by a variety of chemical and physical stimuli. It is not fit for application in clinic. Ischemia postconditioning (PostC) can be triggered during the clinically applicable time period of reperfusion, but it also has the major limitation as an invasive protocol.Remote ischemic postconditioning (RPostC) is another endogenous cardioprotective method. Brief ischemia stimulus on organ or tissue outside of heart would render the heart more tolerant to the subsequential prolonged ischemia. RPostC doesn't need invasive intervention as others do, which may have a promising future in clinical practice. Therefore, the mechanism research of remote ischemic postconditioning induced cardioprotection against ischemia/reperfusion injury is beneficial for the further study and according to which will be helpful to find a new interventions.Myocardium ischemia/reperfusion injury leads to oxidative stress, calcium homeostasis imbalance and cell apoptosis, thereby increasing tissue damage. The normal structure and function of mitochondria have a key role during. the cell apoptosis. Mitochondrial permeability transition pore (MPTP) is one kind of pore on the mitochondrial inner and outer membranes which are involved in the mechanisms of cardioprotection. Opening of the MPTP is thought to be a critical event in mediating the damage to hearts that accompanies their reperfusion following prolonged ischemia. However, the mechanisms of cardioprotection induced by RPostC have not been extensively studied. Here we investigate whether RPostC may as the target for inhibiting apoptosis through the mitochondrial to protect rat heart againist ischemia and reperfusion injury.In the present study, we used two layers (in vivo and in mitochondria) of experimental models to investigated the role of cardioprotection of RpostC and the the mechanism of MPTP, which can offer a few clues to the treatment for clinical ischemia/reperfusion injury.Objective: To observe the effect of RPostC in cardioprotection and investigate the modulation of mitochondrial permeability transition pore.Methods: Anesthetized male Sprague Dawley rats were randomly allocated into the five groups, which are Sham group (n=12), ischemia/reperfusion (I/R, n=12), remote ischemic postconditioning group (RPostC, n=12), remote ischemic postconditioning+ Atr group (RPostC+Atr, n=12) and I/R+Atr group (I/R, n=12). The left anterior descending coronary arteries (LAD) of all rats were encircled with a suture to make a snare after their chests being opened. Except for the Sham group, in the other groups, LAD was ligated for 45min (ischemia) followed by a l80min LAD open (reperfusion) in vivo. In RPostC group,three 5min cycles of lower limb ischemia/reperfusion (femoral artery clamping and declamping) were administered before the onset of myocardial reperfusion. In RPostC+Atr group, atractyloside (Atr, 5mg/kg, a MPTP opener) was intravenously administered 30s before myocardial reperfusion to RPostC group. In I/R+Atr group, Atr was administered for 30s via intravenous before myocardial reperfusion to I/R group. Throughout the experiment, mean arterial pressure (MAP), heart rate (HR), rate pressure product (RPP), and a leadⅡelectrocardiogram were continuously monitored. At the end of reperfusion, arterial blood sample was obtained to quantify plasma activity of lactate dehydrogenase (LDH), creatine kinase (CK). Also, the infarct size was evaluated using the Evans blue and triphenyltetrazolium chloride (TTC) staining. The absorbance of mitochondria at 520nm (A520) which reflects the opening degree of mitochondrial permeability transition was measured by spectrophotometer. Reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression of Bcl-2 and Bax mRNA.Results: Except the Sham group, MAP for other groups, there were no significant differences. However, HR and RPP were significantly decreased at 180 mins, and the levels of ST segment and ventricular arrhythmia during myocardial ischemia/ reperfusion were significantly increased in the I/R group. Myocardial infarct size (percentage infarct size/ area at risk, mean±SD) was reduced by 56% in RpostC (54.6±8.9) compared to I/R (30.6±6.9, p﹤0.05), consistent with a reduction in plasma CK activity (356.5±10.7 vs. 395.7±21.9 U/L, p﹤0.05) and LDH activity (103.0±18.6 vs. 139.7±15.3 U/L, p﹤0.05).However, atractyloside (Atr), a MPTP opener, abrogated the myocardial infarct size reduction in RpostC. The mitochondria were isolated from hearts were treated with each groups. The mitochondria decrease rate in RPostC group at A520 in the mitochondria suspension was remarkably attenuated compared with that of mitochondria from I/R group. However, Atr reduced the effects of RPostC. The reverse transcription-polymerase chain reaction (RT-PCR) technique detected the expression of Bcl-2/ Bax mRNA in I/R (0.21±0.05) and RPostC+ Atr (0.29±0.07) compared with RpostC (0.53±0.07, p﹤0.05), which RPostC and Atr have similar influence on the trend.Conclusions: Remote ischemic postconditioning has the significant protective effect on rat against myocardial ischemia and reperfusion injury, the mechanisms of mitochondrial permeability transition pore might be a pathway for cardioprotection.
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