| Background:Perioperative cardiac complications such as myocardial ischemia and infarction, is the main cause of increased morbidity and mortality in cardiac surgery patients.As soon as possible to restore the blood supply of myocardial ischemia area after acute myocardial infarction occurred, ischemic myocardial injury in ischemia period can aggravate instead., This phenomenon is called as myocardial ischemia-reperfusion injury (IRI). Myocardial ischemia-reperfusion injury is a common clinical anesthesia work of pathological process, especially in heart surgery under extracorporeal circulation, thrombolytic therapy in patients with myocardial infarction and non cardiac surgery in patients with coronary heart disease (CHD) tend to be more rare. Therefore, how to control and manage patients with acute myocardial ischemia-reperfusion injury to save life in perioperative has become an important topic. So far, the mechanism of IRI is not very clear, it consists of three:oxygen free radical, calcium overload and activation of neutrophils. In addition to the three mechanisms, mitochondria damage and energy metabolism disorder are also the important reason of myocardial ischemia-reperfusion injury.Tntracellular ATP level is the main factor of decide cells apoptosis or necrosis. As Murry first proposed myocardial ischemia preadaptation (isehemie preconditioning, IPC) concept in1986, and thinks that the IPC is currently one of the most effective mechanism of endogenous protection..Myocardial ischemic preconditioning is considered as the most iconic gold characteristics of the myocardial ischemia preadaptation protect myocardial. But it is a kind of damage process, and ischemic preconditioning in the best time and number of time limit, safety, and the problem of individual differences that limits its clinical application value. So people put forward to reducing organ damage and producing preconditioning effect of drugs (pharmacologic preconditioning PPC), namely according to IPC mechanism, by the drugs or endogenous substances to decrease IRI simulation method.Dexmedetomidine (DEX) is a new high selective agonists of a2epinephrine. It can inhibite sympathetic nerve excitability, enhance the vagus nerve excitability, with sedation, analgesia, anti anxiety and hypnotic amnesia, hemodynamic stability, and reduce the dosage of anesthetic and opioids and chills, and so on, is widely used in the ICU and the process of operation. In addition to the above role, with in-depth study of the Dexmedetomidine, the researchers confirmed the Dexmedetomidine can support organism to organism many important organs such as heart, brain, kidney, liver, lungsand gastrointestinal tract, has a protective effect. In the process of its protection mechanism, many people think that the Dexmedetomidine play a role mainly through central a2adrenaline receptors. There are also people who believe the Dexmedetomidine protective effect of organism can play by acting on peripheral a2adrenaline receptors, but it is still a lack of reliable basis. Exactly Dexmedetomidine organism is the central or the role in peripheral has not been clearly determined.In a clinical trial v iew of the surgical patients with cardiovascular disease,, the study found that in surgical patients with cardiovascular disease during a given Dexmedetomidine organism can maintain hemodynamic stability, be convenience of intraoperative management, and reduce the occurrence of serious accidents such as myocardial ischemia heart. Some animal experimental study also reported the Dexmedetomidine can reduce the myocardial ischemia-reperfusion injury in votro, playing a role of protection for the heart. But at the moment, the myocardial full-thickness ischemia of special heart protection still of Dexmedetomidine has a lot of controversy. In2007, Hisako Okada et al. In vitro cardiac ischemia rats before25min to Dexmedetomidine and Dexmedetomidine alone or in combination mitotally give Yohimbine (a2) receptor antagonists, show That the Dexmedetomidine can reduce coronary arterial blood flow and myocardial infarct size, the rats in vitro heart plays a protective role, and the cardiac protective effect by a2adrenaline receptor mediated. Similarly, in2010, Soichiro Mimuro in rats in vitro heart after25min to give right before filling the Dexmedetomidine alone or in combination supporting mi totally give yohimbine. Results show that the Dexmedetomidine not only has no effect on hemodynamics and coronary blood flow, increase the myocardial infarction area. Also, Dexmedetomidine in vivo heart ischemia-reperfusion injury of protection is also controversial. Hisako Okada and Hasan Kocoglu think Dexmedetomidine pretreatment reduce myocardial infarction size, may be because the Dexmedetomidine cannot totally reduce coronary outflow caused by myocardial hypoperfusion, triggering the myocardial ischemia preconditioning mechanism. Mauricio Ibacache study also found that the Dexmedetomidine can reduce the ischemia-reperfusion myocardium of rats myocardial infarction area, protect the rat myocardial from damage in vivo and in vitro. He thinks Dexmedetomidine pretreatment could increase the phosphorylation of Erk1/2, Akt and eNOS in pretreatment and reperfusion, the activation of PI3K/Akt/eNOS channel indirectly induced myocardial protection. Specific mechanisms now there is no clear conclusion. Currently, there is no a clear conclusion whether Dexmedetomidine on myocardial ischemia-reperfusion injury is protective, and through what kind of mechanism to play a role, whether peripheral can also play a role.. In order to make it to show the superiority and application value in many fields of clinical practice, and work in clinical anesthesia and CUI plays a more and more important role, our topics as a starting point.Yohimbine (Yohimbine, YOH) is a kind of a2adrenergic receptor antagonist, is the Dexmedetomidine in the high specific antagonists. It prevents the brain center a2adrenergic receptor, so as to prevent and reduce the a2adrenergic agonists. A2adrenergic agonists calm and respiratory inhibition effect can be yohimbine reversal. Yohimbine can also anti-diuretic effect, and increases the heart rate and blood pressure. This experiment using specific a2adrenergic receptor antagonist, yohimbine to explore whether Dex play a protective role by excited a2adrenergic receptors.Objective①Through a variety of indicators to assess damage caused by ischemia reperfusion in rats②Explore the effect of Dexmedetomidine pretreatment on myocardial ischemia-reperfusion injury in rats.Methods①Experimental model Healthy250-300g male SD rats were anesthetized and fixed at the laboratory bench, received endotracheal intubation and mechanical ventilation.Separation the right carotid artery, carotid left ventricular catheter, recording the left ventricular function in rats, and selecting standard II lead connection to record the electrocardiogram, computer software recorded waveform. The left edge of the sternum in the left chest wall intercostal3,4distance of about0.5cm thoracotomy, drill blunt dissection exposed the heart as a symbol to the left coronary vein. Sentenced to6-0without injury sutures in the bottom of the left atrial appendage1-2mm for line knot, about the depth of the needle1.5mm, tighten the ligature so that the left coronary artery occlusion is caused by myocardial ischemia. release ligature reperfusion120min.after myocardial ischemia30min②Groups60healthy male SD rats were randomly divided into six groups (n=10):Sham group (CS group), Ischemia-reperfusion injury group (IR group), Ischemic preconditioning group (IP group), Dexmedetomidine preconditioning group (DP group), Dexmedetomidine+Yohimbine pretreatment group (DY group), Yohimbine pretreatment group (YP group).③Detection Indicators Hemodynamic Parameters (HR and MAP) and Heart Function Parameters (LVDP, LVEDP and±dp/dtmax in) are recorded at different time points before and after ischemia-reperfusion. detect the incidence of arrhythmia and calculate the score; observe myocardial histopathological changes of each group; detect CK and LDH of serum at the end of the perfusion; detect myocardial tissue content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity; calculate myocardial infarct size at the end of reperfusion.Results①hemodynamic changes After thoracotomy, with the extension of experimental time, heart rate and mean arterial pressure in each group are reduced. Compared with CS group, the IR group heart rate and mean arterial pressure decreased significantly (P<0.05), the DP group heart rate began to significantly decline after Dexmeditomidine preconditioning, but the decline in mean arterial pressure is not so obvious relative to the IR group, especially mean arterial pressure DP group is higher than the IR group at the end of reperfusion.There is a statistically significant difference between the two groups, while no statistically significant difference between the average DY group and YP group arterial pressure with IR group group.②Changes in left ventricular function After thoracotomy, with the extension of the experimental time, the left ventricular of each group function will reduce. Compared with the CS group, IR group left heart function indicators suggest that left ventricular function reduce a statistically significant difference between the CS group and IR group group. Relative to the IR group, the DP groups LVDP and±dp/dtmax increased, LVEDP decreased (P<0.05). Relative to the DP group, DY group and YP group±dp/dtmax reduce, LVEDP increased (P<0.05), Dexmedetomidine specific antagonist-yohimbine reversed right Dexmedetomidine protection effect (P<0.05), the experimental results with statistical significance.③The incidence of arrhythmia and arrhythmia score Relative to CS group, IR group arrhythmia incidence and increased severity of arrhythmias. Relative to the IR group, the DP groups arrhythmia incidence and arrhythmia score lower statistically significant difference between the groups, and specific antagonists right Dexmedetomidine-yohimbine reversed Dexmedetomidine protection effect (P<0.05), the experimental results with statistical significance.④Myocardial histopathological changes Compared with the CS group, IR group biopsy was regional degeneration and necrosis of the muscle fibers arranged in disorders of the lesion, myofilament fracture dissolution, cell swelling, some karyopyknosis even fragmentation, interstitial edema, myocardial tissue inflammatory cell infiltration; compared with IR group,DP group rats myocardial biopsy is closely connected to the myocardial tissue structure clear muscle fibers, tissue congestion, edema, inflammatory cells decreased.⑤CK and LDH levels in serum Compared with CS group, IR serum CK and LDH content increased (P<0.05); compared with IR group, DP serum cardiac enzymes CK and LDH decreased (P<0.05). Dexmedetomidine specific antagonist Yohimbine can reverse Dexmedetomidine protective effect (P<0.05), and the experimental results are statistically significant.⑥Myocardial tissue MDA content of myocardial tissue homogenates increased SOD activity decreased (P<0.05) in IR group; compared with IR group, DP group myocardial tissue homogenate MDA content increased, SOD activity decreased (P <0.05). Dexmedetomidine specific antagonist-Yohimbine can reverse protective effect of Dexmedetomidine (P<0.05), and the experimental results are statistically significant.⑦Myocardial infarct size Compared with CS group, myocardial infarct size of IR group at the end of reperfusion was significantly increased (P<0.05); compared with IR group, DP group at the end of reperfusion, infarct size was significantly reduced (P<0.05). Dexmedetomidine specific antagonist-Yohimbine can reverse protective effect of Dexmedetomidine (P<0.05), and the experimental results are statistically significant.Conclusion①Myocardial ischemiareperfusion lead to myocardial injury rats in vivo;②Dexmedetomidine pretreatment can effectively reduce ischemia-reperfusion injury of the rat in vivo, have a protective effect on rat heart;③Dexmedetomidine specific antagonist-Yohimbine can reverse effect of dexmedetomidine on myocardial ischemia-reperfusion injury in rats. |
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