| BACKGROUNDMyocardial stunning(MS),a post-ischemia myocardial malfunction,usually occurs after the attack by either unstable or overwork-induced pectoris angina.It also happens following various interventional cardiac operations.Lasting MS can eventually cause serious heart failure,even death.Thus,seeking for the effective therapies to prevent and treat MS has become a global hot focus.Previous studies showed that acupuncture can improve the myocardial ischemic injury.But it's difficult for acupuncture to exert its ameliorative effect on the myocardial ischemic damage due to that the patients attached acutely by myocardial ischemia such as coronary heart disease rarely came to see acupuncturist.Comparatively,MS is more operable to be treated by acupuncture as compared with other acutely-attacking myocardial ischemia because of that patients with MS are not acutely attacking and the state of the illness is relatively milder.However,no study has been reported so far on the improvement of MS by acupuncture.Researches on acupuncture analgesia suggested that acupuncture can increase opioids production and activate opioid receptor system.Furthermore,Modern medical studies have shown that there are a large number of opioid receptor systems mainly composed of K-opioid receptor(?-OR)in myocardial cell membrane and vascular wall.It was also found that ?-OR exogenous activation could inhibit myocardial infarction or myocardial arrest,?-OR agonist could mimic ischemic preconditioning to improve ischemic myocardial damage,and the antagonist of opioid receptor could block the protective effect of ischemic preconditioning.It's reasonable that acupuncture may activate opioid receptors and their signaling pathway to ameliorate the MS-induced myocardial ischemic malfunction.However,so far,the related research work mentioned above has not been reported.OBJECTIVE AND SIGNIFICANCEThe aim of the present study was firstly to confirm the ameliorative effect of electroacupuncture pretreatment on myocardial ischemic injury induced by MS in animal model and then to explore potential contribution of ?-OR in mediation of the effect.The completion of the study will not only provide the scientific basis on effective amelioration produced by acupuncture on the myocardial malfunction caused by MS but also provide a new idea or breakthrough point for the study of mechanism of acupuncture in improving ischemic myocardial injury.Therefore,it will create a new operable way for using acupuncture to treat myocardial ischemic disease in clinic.METHODSIn this study,myocardial stunning model induced by transient myocardial ischemia reperfusion was used as the research object,and the protective effect of electroacupuncture pretreatment on myocardial stunning was observed by electrocardiogram(ECG)and in vivo hemodynamic analysis.Furthermore,the effect of electroacupuncture pretreatment on myocardial stunning was further investigated by using ?-OR specific agonist to explore whether ?-OR receptor was involved in electroacupuncture pretreatment.Clean grade healthy SD rats were used in the experiment.They were randomly divided into normal control group(group N),myocardial stunning model group(group M),electroacupuncture pretreatment group(group EA)and nor-BNI group(group BNI)The rats in group EA was treated with electroacupuncture at both sides of'Neiguan acupoint(PC 6)for 30 minutes before myocardial arrest(EA parameter:0.5 mA,2/15 Hz).Nor-BNI was injected into the left femoral vein of rats in group BNI 10 minutes before electroacupuncture.In order to determine the protective effect of electroacupuncture pretreatment on myocardial ischemic injury induced by MS,ST segment in electrocardiogram(ECG)and Hemodynamic parameters such as left ventricular systolic pressure(LVSP),left ventricular ejection fraction,left ventricular stroke power and maximum rate of left ventricular pressure rise(dp/dt max)were measured,Moreover,combined with the application of ?-OR specific agonist,i.e.nor-BNI,the role of ?-OR receptor in ameliorating myocardial stunning was investigated.RESULTS1.Effects of electroacupuncture pretreatment on myocardial stunning.1.1 Changes of ST segment in ECG:There were no statistical differences in ST segment level at TO time point in each group(all P>0.05).The ST segment amplitudes in group N were relatively stable at each time point.The ST segment amplitude in group M was maintained in higher level at each time point after ligation compared with its own TO value.Compared with the corresponding ST segment amplitude in group N,the ST segment amplitude after T2 increased significantly(P<0.05 and P<0.01).The ST segment in group EA gradually returned to the corresponding level of group N at each time point after T2.The amplitude of ST segment in group EA was significantly lower than that in group M(P<0.05 and P<0.01).1.2 Changes in hemodynamic indicators1.2.1 There were no significant differences in the initial state of left ventricular systolic pressure in each group(P>0.05).There was no significant fluctuation of left ventricular systolic pressure in group N at every time point.The pressure increased slightly after ligation in group M from T3 onwards,but it remained at a lower level.Compared with its TO value,there was a significant decrease(P<0.01),and compared with group N,left ventricular systolic pressure also decreased significantly at corresponding time points(P<0.05 and P<0.01).Although there is a downward trend in group EA after ligation,only Tl,T2 and T3 are significantly different from their TO values(P<0.05 and P<0.01).On the other hand,the left ventricular systolic pressure continued to rise from T2 time point and gradually returned to the level in group N(all P>0.05),and at each time point after T3,the left ventricular systolic pressure increased significantly compared with that at corresponding time point in group M.1.2.2 Changes of left ventricular ejection fraction:There were no significant differences in left ventricular ejection fraction at TO time point in each group(all P>0.05).The left ventricular ejection fraction in group N had relatively stable at each time point.The left ventricular ejection fraction level in group M stayed in low level which compared to its own TO time point after ligation(all P<0.01),and compared with group N,there were significant decrease at each time point(all P<0.01).The left ventricular ejection fraction in group EA increased gradually after T2,and there was no significant difference between group N and group EA(all P>0.05),and at each time point after T2,they were significantly higher than that in group M(all P<0.01).1.2.3 Changes of maximum rate of rise in left ventricular pressure:There were no significant differences in the maximum rate of rise in left ventricular pressure at TO time point in each group(all P>0.05)and no significant fluctuation of the maximum rate of rise in left ventricular pressure in group N at every time point.The maximum rate of rise in left ventricular pressure in group M continuous decreased,and this declination was an obviously declination compared with group M at TO and group N at each time after ligation(all P<0.01).The maximum rate of rise in left ventricular pressure in group EA increased gradually after ligation.Although compared with group N was still declined,however,at the T5 time point,the maximum rate of rise in left ventricular pressure of group EA was significantly higher than that in group M(P<0.05).1.2.4 Changes of left ventricular stroke work:There was not any statistical difference in left ventricular stroke work at TO time point in each group(all P>0.05).The left ventricular stroke work in group N remains relatively stable at each time point.The left ventricular stroke work in group M were significantly lower than that in group N at each time point after ligation(all P>0.01).The left ventricular stroke work in group EA rose continuously after T2,and gradually returned to its the base value,and compared with the corresponding time points in group M,there were significant improvements(all P<0.01).2.Effects of ?-opioid receptor specific antagonist on protective effects of electro-acupuncture pretreatment with myocardial stunning2.1 Changes of ST segment in ECG:There were no significant differences in the initial state of ST segment between group EA and group nor-BNI(P>0.05).The ST segment in group nor-BNI stayed at a higher level at each time point after ligation,and there were significantly higher than its own TO value(all P<0.01).After T2,there were significant differences in ST segment level at each time.point compared with EA group(all P<0.01).2.2 Changes in hemodynamic indicators:2.2.1 Change of left ventricular pressure:The left ventricular systolic pressure in the group in nor-BNI maintained at a low level at all time points after ligation and there were significantly different compared with its own TO value(all P<0.01).After T3,the left ventricular systolic pressure at each time point were significantly lower than that in group EA(all P<0.05).2.2.2 Changes of left ventricular ejection fraction:The maximum rate of rise in left ventricular pressure at all time points after ligation in group nor-BNI was significantly reduced,and there were significant differences between its own TO value(P<0.05 and P<0.01).However,the maximum rate of rise in left ventricular pressure at each time point after T3 had a downward trend compared with the corresponding values of group EA,but there were no statistical differences between the two groups(all P>0.05).2.2.3 Changes of the maximum rate of rise in left ventricular pressure:The maximum rate of rise in left ventricular pressure was significantly decreased at different time points after ligation in the nor-BNI group.There was significant difference between the two groups in resting state(P<0.05 and P<0.01).However,the maximal rate of left ventricular pressure at each time point after T3 time point had a downward trend compared with the corresponding values of EA group,but there was no significant difference between the two groups(P>0.05).2.2.4 Changes of left ventricular stroke work:The changes in left ventricular stroke work at different time points after ligation were lower than its own TO value(P<0.05 and P<0.01).Furthermore,compared with EA group,the left ventricular stroke work in group nor-BNI at each time point after T2 were also significantly decreased(P<0.05 and P<0.01).CONCLUSION1.Electroacupuncture pretreatment can obviously inhibit the abnormal elevation of ST segment in ECG,increase left ventricular ejection fraction,increase left ventricular contractility,and improve left ventricular power.It has certain protective effect on myocardial ischemic injury induced by myocardial stunning.2.Nor-BNI,the specific antagonist of Kappa-opioid receptor,could partially block the protective effect of electroacupuncture pretreatment on myocardial stunning,especially for ST segment and left ventricular pressure at every time point after 60 minutes of reperfusion.The inhibitory effects of four indexes of left ventricular stroke work and left ventricular ejection fraction were significant,suggesting that ?-opioid receptor signal transduction system may be involved in electroacupuncture pretreatment to ameliorate ischemic injury induced by myocardial stunning. |
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