| BackgroundThe ischemic heart disease is the leading cause of death worldwide, and 3.8 million men and 3.4 million women die of the disease each year. After an acute myocardial infarction, early and successful myocardial reperfusion is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. However, numerous studies have shown that reperfusion itself may enhance the injury, resulting in extension of infarct size after ischemia (ie, ischemia-reperfusion [IR] injury). Despite optimal myocardial reperfusion, the rate of death after an acute myocardial infarction approaches to 10%, and the incidence of cardiac failure after an acute myocardial infarction is almost 25% of myocardial reperfusion. So,the most difficult problem is how to gain the best efficacy from reperfusion in ischemic myocardium.Myocardial IR injury causes four types of cardiac dysfunction.â‘ Myocardial stunning:the myocardium usually recovers from this reversible form of injury after several days or weeks.â‘¡No-reflow phenomenon:while the recovery of the blood perfusion of the organs, but the perfusion area organizations have emerged the phenomenon of non-reperfusion.â‘¢Reperfusion arrhythmias:refers to that the blood flow in acute ischemic myocardium can be restored once again appeared in a few seconds which may lead to a brief acceleration of idioventricular rhythm, ventricular tachycardia, atrioventricular or bundle branch block suddenly disappeared or a transient sinus bradycardia, sinoatrial block, etc. These arrhythmias, especially ventricular arrhythmias, can often lead to patient's hemodynamic change which is one of the causes of death broken and is potentially harmful, but effective treatments are available.â‘£Lethal reperfusion injury:refers to reperfusion leading the survival of cardiac cell to death. Lethal reperfusion injury independently mediated cardiac cell death, and increased the size of myocardial infarction,which was the most serious type in myocardial ischemia/reperfusion injury, so it prompted us to study the myocardial ischemia/reperfusion injury-related cell death.The programmed cell death is a kind of gene regulation, highly ordered, active cell death process and thus programmed cell death is considered controllable. So, programmed cell death may be inhibited. Therefore, programmed cell death in myocardial ischemia/reperfusion injury attracts everyone's attention. 1. Single-use blocking agents against each of the three kinds of programmed cell death can be significantly reduced infarct area. This shows that all three kinds of programmed cell death in rat myocardium/ischemia-reperfusion injury play an important role. Among them, using z-VAD-fmk can most obviously reduced infarct size of myocardial infarction, indicating that apoptosis may play the most an important role, roles of autophagy and necroptosis have no significant difference.2. There was no statistical difference of the myocardial infarct area between respectively combined blocking two kinds of programmed cell death and separated blocking apoptosis, but there was a trend to further reduce myocardial infarction size.3. Joint blocking apoptosis, autophagy and necroptosis can significantly reduce infarct size.4. Joint blocking apoptosis, autophagy and necroptosis can significantly improve the cardiac function in 48 hours after rat myocardium ischemia/reperfusion, but the remaining blocker group had improved cardiac function trend.Conclusion:1. The occurring of autophagy is the earliest of the three types of programmed cell death caused by rat myocardial ischemia/reperfusion injury. In the period of ischemia it increased, and further increased during reperfusion; in the early period of reperfusion, apoptosis occurred. It reached the peak at 1 hour after reperfusion, then began to decline. Necroptosis is the latest, and it happened about 12 hours after reperfusion,24 hours later reached the peak,48 hours after the reperfusion still did not return to the normal.2.In myocardial ischemia/reperfusion of rats, the inhibition of apoptosis may contribute to autophagy and necroptosis; inhibiting autophagy may promote apoptosis; inhibiting necroptosis might had no significant effect on the other two kinds of programmed cell death.3. Three kinds of programmed cell death all play important role in rat myocardium/ ischemia-reperfusion injury, and the role of apoptosis may be the most important. The roles of autophagy and necroptosis have no significant difference.4. Jointing blocking of apoptosis, autophagy and necroptosis can reduce infarct size and improve cardiac function in the rat myocardium/ischemia-reperfusion more effectively than the single blocking of one programmed cell death of them. |
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