Effect Of Percutaneous Coronary Intervention On Left Ventricular Remodeling After Acute Myocardial Infarction

BackgroundsMany compensatory mechanisms start after acute myocardial infarction,and left ventricular remodeling begins at the same time,which includes that ventricular wall with the infarcted myocardium goes thin and stretched,then produces bulging,and ventricular wall without infarcted myocardium goes reactive hypertrophy and elongation,which results in left ventricular progressive expansion,deformation and cardiac insufficiency.In the process of left ventricular remodeling after acute myocardial infarction, not only the myocardial cell's structure, metabolism and function but also the extracellular matrix become abnormal. Extracellular matrix is hydrolyzed by the matrix etalloproteinases in the dynamic balance of degradation and reorganization,and tissue inhibitors of metalloproteinases is the endogenous specificity inhibitor to it.The therapy of coronary reascularization and myocardial reperfusion, including thrombolysis and acute percutaneous coronary intervention, have been implemented early,which can save ischemic myocardium, narrow infarction area and protect left ventricular function most effectively.The aim of the present study is to contrast different effect of primary percutaneous coronary intervention,delay PCI and conservative treatment on left ventricular remodeling and heart function after acute myocardial infarction.we reveal the expression of matrix etalloproteinases and tissue inhibitors of metalloproteinases after acute myocardial infarction,and the correlationship between MMPs and left ventricular remodeling and heart function, so as to explore predictive value of the MMP-9,TIMP-1 on left ventricular remodeling and heart function.What' more,we'll probe into other molecular biology mechanism in the precautionary effect of PCI on left ventricular remodeling,in terms of influence of PCI on the expression of MMPs and TIMPs.Objective1,To contrast different effect of primary PCI, delay PCI and conservative treatment on left ventricular remodeling after acute myocardial infarction, which can guide clinical treatment, and help us get a reasonable selection of treatment.2,To reflect the expression of matrix etalloproteinases and tissue inhibitors of metalloproteinases after acute myocardial infarction,and the correlationship between MMPs and left ventricular remodeling and heart function. Definitely, to explore the relationship of the MMP-9,TIMP-1 and index standing for left ventricular remodeling and heart function, for example, left ventricular end diastolic diameter (LVDD),left ventricular end diastolic and end systolic volume (EDV and ESV),left ventricular ejection fraction (LVEF) and the formation of ventricular aneurysm.So as to explore the predictive value of the MMP-9 and TIMP-1 on left ventricular remodeling and heart function. 3,To study other molecular biology mechanism in the precautionary effect of PCI on left ventricular remodeling,in terms of influence of PCI on the expression of MMPs and TIMPs. Reperfusion executed as soon as possible is the key to treat AMI. PCI can limit infarction range, restore hibernate myocardial reperfusion, promote the healing myocardial infarction and prevent infarcted myocardium extending and ventricular remodeling. What's more, we'll probe into other molecular biology mechanism in the precautionary effect of PCI on left ventricular remodeling,in terms of influence of PCI on the expression of MMPs. At last we'11 proclaim specific mechanism of left ventricular remodeling,which may be the new target of medication for the left ventricular remodeling.Methods1,Object of Study and Grouping Ninety-eight patients with a first acute myocardial infarction were enrolled from March 2010 to Novenber 2010 in Cardiology of Wuhan General Hospital. All of the ninety-eight cases contained seventy men (71.4%) and twenty-eight women (28.6%).Fifty-one patients (group A) were performed primary PCI before 12 hours from onset of symptoms. Twenty-two patients (group B) after 12 hours from onset of symptoms were performed delayed PCI, and twenty-five patients (group C) got conservative therapy. The other twenty patients (group D) composed control group with no obvious stenosis by the CAG (coronary arteriongraphy). There were no significant difference between four groups in sex,age,complication,risk factors,the proportion of two kinds of AMI and locations of myocardial infarction,which were comparable.Diagnostic criteria:1,AMI:any two of the following three requirements:the typical symptoms of chest pain; st-segment elevation is equal or greater than 0.2 mV in thoracic lead or 0.1 mV in limb lead in two nearby leads in electrocardiogram; Phosphoric acid creatine kinase isozyme is more than twice the normal value; (2) Diabetes is diagnosed according to the ADA 2007 version of standard treatment: Patients with past use of oral hypoglycemic agents and insulin or secondary insulin fasting plasma glucose≥7.0mmol/L, then diagnosed diabetes; (3) Diagnostic criteria for Hypertension adopted in 1999 the World Health Organization/International Society of Hypertension League (WHO/ISH) standard:Without the use of antihypertensive drugs, the systolic blood pressure≥140mmHg, diastolic blood pressure≥90mmHg; past history of high blood pressure, antihypertensive drugs currently in use are not up to the level of blood pressure should be diagnosed as having hypertension; (4) Diagnostic criteria of Hyperlipidemia adopted the Dyslipidemia Control Strategies Thematic Group "proposed standard for prevention and treatment of dyslipidemia":TC≥5.72 mmol/L, TG≥1.7 mmol/L, LDL≥3.64 mmol/L, HDL≤0.91 mmol/L.Exclusion criteria:except for the patients with recurrence of AMI, thrombolysis, co-nnective tissue disease,secondary cardiac rupture, myocardial perforation, rupture of chordae tendinca, serious valvular disease, a traumatic cardiopulmonary resuscitation (CPR),severe liver and kidney dysfunction,active hemorrhage, hypersensitive to co-ntrast agent, trauma, cancer, major surgery, varieties of infections or it's not clear when persistent chest pain begins,etc.Success Criteria of PCI:It is compared to a successful operation when the residual stenosis<20% by visual after stenting and the blood level was TIMI3 (CAG assess-ment),and there are no serious complications.2. Definite Methods2.1 All patients admitted to hospital were timely collected their medical history and symptoms, and examined physical, serum myocardial enzyme and electrocardiogram. If there is no contraindication, everyone should be given Strengthening medications, containning aspirin, clopidogrel, nitrates, angiotensin 1-converting enzyme inhibitors or angiotensin receptor inhibitors,beta blockers, statins etc.Group A was given aspirin tablets 300mg and clopidogrel 600mg oral before coronary arteriography and emergency PCI(Innova 2000 Cardiovascular Im aging System)。Group B was given delay PCI; Group C was given conservative treatment. All patients after PCI got Aspirin Enteric-coated Tablets 300mg and clopidogrel 75mg oral once a day,and from 3 months after PCI got Aspirin Enteric-coated Tablets 100mg and clopidogrel 75mg oral once a day at least one year.(insist on taking in the Follow-up period)2.2 Observation and evaluationVenipuncture for collection blood 6ml at hospitalization, onset 1 hour,7d and 90d, then centrifuge at 3000r/min about ten minutes;the plasma levels of MMP assay were analyses.Immediately sent them to our laboratory department, and detected the relevant indicators by qualified automatic biochemical locator:Plasma total cholesterol (TC), Triglycerides (TG), high-density lipoprotein cholesterol (hdl-c), low density lipoprotein cholesterol (LDL-C),fasting plasma glucose (FPG),etc.Preservat-ed supernatant in refrigerator at -80℃, then detected serum MMP-9(examination area0-10ng/ml) and TIMP-1(examination area0-10ng/ml), in strict accordance with operating instructions,in enzymoimmunoassay. Wuhan Boster bio-engineering limited company offered the reagent. All of the patients were detected related indicators expressing cardiac function by echocardiography at 7 to 10 days after admission and 3 months(instruments is Agilent HP5500 echocardiographic diagnosis, Probe frequency2-4MHz). Bi-planar or Simpson methodcalculate left ventricular end diastolic diameter (LVDD),left ventricular end diastolic and end systolic volume (EDV and ESV),left ventricular ejection fraction (LVEF) and the formation of ventricular aneurysm.2.3,Percutaneous Coronary Intervention Surgical MethodsPCI is completed by cardiology specialist according to the The American College Of Cardiology and the American Heart Association (ACC/AHA) guidelines coronary angiography using Judkins method, conventional multi-position (left anterior oblique, right anterior oblique, and axial position cephalopods) projection, in order to make the paragraphs of coronary fully display. Vascular will be judged as target lesion vessel when visually diameter stenosis≥70%, usually through the femoral artery approach, according to standard methods of drug-eluting coronary stent implantation. It is compared to a successful operation when the residual stenosis<20% by visual after stenting and the blood level was TIMI3 (CAG assessment).3.Statistical AnalysisDatas was processed and analysed by SPSS 13.0 statistical software. All measurement datas were expressed by mean±SD. One-Way ANOVA was used to compare the mean among the three groups as measurement data; multiple comparison by Games Howell (Heterogeneity of variance)或LSD (homogeneity of variance);Paired-Samples T Test or Repeated Measures was used to compare the mean before and after treat; chi-square test was used in enumeration data; the Pearson line correlation analysis was used to detect correlation between index. P<0.05 indicated that the difference was statistically significant. The experimental results were described by tabulation.Results1.Comparison of baseline clinical datas between the four groupsThe sex, age, proportion of complicating with diabetes, hypertension, hyperlipe-mia and patients with a history of smoking,the proportion of two kinds of AMI and locations of myocardial infarction were not significantly different between the four groups before PCI (P>0.05).2. Results of Serum MMP-9 and TIMP-1The concentration of serum MMP-9 and TIMP-1 at hospitalization were significant-ly different between the three groups and the control group (P<0.05).Serum MMP-9 in group A increased again after PCI, and decreased to near normal level at 7d, which was significantly different to B and C groups. But Serum TIMP-1 still exceeded to the control group at 7d,and decline at 90d. Serum MMP-9 in group B at 7d exceeded it significantly at the time of admission,and fell to the level of admission at 90d,which was significantly different to group C (P<0.05), serum TIMP-1 exceeded to the control group all along, the concentration of serum.MMP-9 and TIMP-1 in group C passed the control group significantly (P<0.05)3.Results from echocardiography.There were no significant difference among group A,B and C in LVEF,EDV,ESV and LVDd by echocardiography at 7d.The improvement of EDV,ESV,LVDd and LVEF at 90d were statistically significant between A and C groups, the same to B and C groups,but there was no difference between A and B groups (P>0.05). The improvement of EDV,ESV,LVDd in group A and B at 90d were statistically significant to them at 7d,but LVEF wasn't although it got better.The enlargement of EDV,ESV,LVDd in group C at 90d were statistically significant to them at 7d,and LVEF was declined significantly.Ratio of ventricular aneurysm formation increased in group A,B and C at 90d than at 7d,but there was no significance among the three groups.4. The correlation between density of MMP-9 and results by echocardiographicThe correlation between average serum level of MMP-9 at 7d and EDV,ESV at 90d was positive(r值0.261, P<0.05;r值0.340, P<0.05),and it was negative between average serum level of MMP-9 and LVEF(r值-0.218,P<0.05),and there was no relevance between it and LVDd(r值0.118,P>0.05).Conclusion1.Serum MMP-9 in patients with AMI increases and lasts for one week or several months, but PCI can lower it and shorten the time of it;2.During LVRM after AMI,the correlation between average serum level of MMP-9 and EDV,ESV is positive,and the correlation between average serum level of MMP-9 and LVEF is negative. Serum level of MMP-9 become a predictor of heart attack and LVRM after AMI; 3. Direct PCI openning infarct-related artery as early as possible can improve heart function, and delayed PCI can also inhibit left ventricular remodeling;4. EDV,ESV,LVDd are more sensitive than LVEF and ratio of ventricular aneurysm formation in the early stage of left ventricular remodeling after AMI.