Experimental Studies On The Changes Of The Expression Of Angiotensin Ⅱ Receptor In Rat Hearts After Myocardial Stunning

BackgroundMyocardial ischemical reperfusion(IR) injury is a common phenomenon that severe injury occurs in ischemical cardiac muscle after reperfusion,even irreversible injury.It includes four phenomenons:1,reperfusion arrhythmia(RA);2,myocardial stunning(MA);3,injury of blood vessel;4,accelerated myocardiolysis.when myocardial ischemia occurs,local rennin-angiotensin system(RAS) produce more angiotensinⅡ(AngⅡ).It's function is mainly carried by angiotensinⅡtype 1 receptor AngiotensinⅡcan regulate coronary vessels tension,promote coronary vessels constriction and spasmodism,and degrade blood reservation of coronary vessels; increase the incidence and duration of reperfusion arrhythmia,aggravate heart function damage;increase the releasing of creatine phosphokinase(CPK) and lactate dehydrogenase(LDH),and also the accumulation of lactic acid;aggravate ischemical reperfusion injury.Left ventricle dysfunction after myocardial ischemia and myocardial ischemical reperfusion decrease quality of life and survival rate of patient.Researches have indicated that rennin-angiotensin system(RAS) is activated after myocardial ischemia and myocardial ischemical reperfusion which promote the pathological and physiological changes of ischemical reperfusion(IR) injury.Myocardial stunning is also called postischemic myocardial dysfunction.It is a constant state of myocardial chemical dysfunction after ischemical reperfusion notwithstanding coronary blood flow is normal or nearly normal,and irreversible injury isn't found id cardiac muscle.In clinical work myocardial stunning is often seen in some conditions:1,acute myocardial infarction(AMI) after early reperfusion:after successful thrombolysis or acute percutaneous transcoronary angioplasty(PTCA) or stent treatmemt,recovery of coronary blood flow can save some nearly necrotic cardiac muscle so that to decrease transmural myocardial infarction area or only display subendocardial myocardial infarction.Because of myocardial stunning,the recovery of heart function doesn't occur immediately but occurs gradually after some days;2,unstable angina pectoris(UAP):the patients often have transient but severe myocardial ischemia and can due to myocardial stunning;3,variant angina pectoris(VAP,Prinzmetal angina):signal attack and immediately receiving vasodilating agent can always lessen myocardial stunning;4,movement induced myocardial ischemia:additive effect of short period multiple myocardial ischemia can due to severe myocardial dysfunction;5,small area of acute myocardial infarction with unable explanatory left heart failure:the possible reason is one side coronary vessel obstruction due to reflected other side coronary vessel spasm,this may cause post-ischemic dysfunction;6,percutaneous transcoronary angioplasty(PTCA);the balloon can completely block coronary vessels and cause myocardial ischemia so that it may develop into myocardial stunning;7,after heart transplantation surgery:before heart transplantation surgery whole heart ischemia and myocardial ischemical reperfusion,after surgery transient hemodynamics instability is often seen,it is correlated with myocardial stunning.AgiotensinⅡtakes a diversify functions in many organs all over the body.This function is performed by AgiotensinⅡreceptor,it can regulate blood pressure, Water-Electrolyte metabolism and participate pathologic myocardial hypertrophy.Recently it can be classified into two subtypes:angiotensinⅡreceptor 1 and angiotensinⅡreceptor 2. This research aims to study the expression of angiotensinⅡreceptor and the change of it's function when myocardial stunning,classify it's molecule mechanism.This will not only give us a more clear knowledge of ischemical heart disease but also develop a prophylactic treatment.With the progress of molecular biology and pharmacology,we will have a clear recognition of angiotensin receptor's role in ischemical heart disease,and this will be profitable for the prevention and treatment of ischemical heart diseases.Objectives(1)To explore the method of preparation of experimental myocardial stunning mode in rats,;(2)divide into groups of different time after ischemical reperfusion;(3)detect the expression of angotensin receptor in stunned cardiac muscle through immunohistochemistry(IHC) method.This study is aimed at study the function, distribution and expression of angiotensinⅡand it's two subtypes angiotensinⅡreceptor 1 and angiotensinⅡreceptor 2.Methods:48 male SD rats were randomly divided into six groups:A group(negative control group),B group(1 hour after reperfusion in stunned myocardium),C group(4 hours after reperfusion in stunned myocardium),D group(8 hours after reperfusion in stunned myocardium),E group(24 hours after reperfusion in stunned myocardium) and F group(3 days after reperfusion in stunned myocardium).Before surgery we give rats normal diet and their weight ranges from 240 grams to 250 grams.Each rat receives general anesthesia and tracheal intubation,contacts synchronous electrocardiogram(BL—420E biologic functional experimental system).To make MS model,thorax was opened,and the LAD(left anterior descending coronary artery) was ligated.After 15 or 20 minutes' the ligature was removed.The successful sign was cyanosis in anterior wall of left vetrcular or tuned into amethyst,and S-T segment was raised or ORS wave was heightened in ECG..In each group,rats were killed to have for the heart sample.The section was stained by HE in order to observe myocardial muscle stucture.Immunohistochemical study have been done in order to determine dynamic expression of ATR1 and ATR1Results:There was no conspicuous change in myocardial muscle stucture in MS mode.The dynamic expression of ATR1 and ATR2 was heightened in early stage,but after 3 days there was a decreasing tendency.So it is possible beneficial fot the recovery of stunned myocardium to block up the function of ATR1Conclusions:After myocardial stunning in rats,ATR1 will achieve it's peak amplitude after 4 hours,and ATR2 will achieve it's peak amplitude after 1 hour,soon after there will be a descending tendency.