Experimental Study Of Evaluation Of Left Ventricular Systolic Function After Acute Myocardial Infarction In Rats And Intervene With 3-AB By Quantitative Tissue Velocity Imaging

BACKGROUND AND PURPOSE Acute Myocardial Infarction(AMI) is an important cardiovascular disease with high mortality and morbidity clinically.The morbility of AMI is the top1 reason account for cardiovascular disease.Survivor of the AMI may recurrence or come with serious complication such as heart failure.The mortality of AMI combined with heart failure may reach 80%.Studying on the myocardial function and its left ventricular(LV) global and regional function dynamic changing during ischemia is essential to diagnose coronary artery disease accurately in early stage and assess the prognosis of patients.Quantitative Tissue Velocity Imaging (QTVI) is one of the echocardiographic technique of Tissue Doppler Imaging, it can apply different myocardial segments velocity trace in the whole cardiac cycle synchronously.It is a promising measuring that can acquire the velocity data of myocardial segments non-invasive and quantitatively.Poly(ADP-ribose) polymerase(PARP) is a nuclear enzyme present in eukaryotes, functions as a DNA damage sensor and a signal transduction molecular,has been implicated in DNA repair and maintenance of genomic integrity.Cellular ischemia and anoxia causes DNA damage,then PARP activation.Severe DNA damage leads to overactivation of PARP,resulting ATP depletion and necrotic cell death. PARP inhibitors,such as 3-Aminobenzamide(3-AB), can depress the ATP consuming during DNA repairing, may prove useful for the therapy of multiple organ ischemic diseases,as has been shown in preclinical animal models.At present,the model of myocardial infarction in rats is a ripe animal model that used for the basic study of pathophysiology and the evaluation of drug effect on ischemic heart disease. In this study,we analyzed the QTVI patterns and regional myocardial velocity trace in myocardial infarction rats model,PARP inhibitor 3-AB was used during ischemia process,and its potential myocardial protective functions against ischemia injury was evaluated by QTVI.The aims are to establish the feasibility of QTVI evaluation in myocardial infarction rats model,and assessing the drug effect.at the same time,to provide experiment evidence of 3-AB as therapeutic candidates for the management of myocardial ischemia injury.This thesis is composed of two parts:PART 1. Experimental study of evaluation on left ventricular regional function by quantitative tissue velocity imaging after myocardial infarction in ratsTo investigate the value of QTVI in evaluating LV morphological and function changes in rats before and post myocardial infarction. Myocardial infarction group, female Wistar rats(n=12), ligation of the main branch of left coronary artery; sham-operated group (n=10),before and 1 week after the operation, echocardiaogra -phy scan was performed in each group. All the rats are sacrificed to measure the LV end-diastolic diamete(rLVEDD)and LV end-diastolic volume(EDV).Results Compared with sham-operated group, the LV end-systolic diameter(LVESD)in the myocardial infarction group were significantly increased (P<0.01), The LV anterior wall end-diastolic diameter(LVAWd), the parameters of LV systolic function(FS),ejection fraction(EF) and sphericity index(SI) were all significantly decreased (P<0.01). The peak radial velocity at the segment of anterior interventricular septum significantly decreased (P<0.01).The peak systolic longitudinal velocity at mitral annulus and segments of left ventricular lateral wall in infarcted group were also significantly decreased (P<0.01).The mean peak systolic velocity at mitral annulus correlated positively to left ventricular ejection fraction and sphericity index(r=0.88,0.79,P<0.01).The LV end-diastolic diameter(LVEDD) and LV end-diastolic volume (EDV)measured by ultrasound and those measured by autopsy both match well. PART 2. Experimental study of evaluation of the effects of 3-Aminobenzamide on left ventricular systolic function after acute myocardial infarction in rats by quantitative tissue velocity imagingTo assess the effects of 3-Aminobenzamide(3-AB) on LV systolic function after acute myocardial infarction in rats by quantitative tissue velocity imaging and two-dimensional echocardiography.After ligation of the main branch of left coronary artery,24 female Wistar rats were finally assigned to two groups:3-AB group (n=14), acute myocardial infarction control group (n=10).Two weeks after treatment with 3-AB, echocardiography was performed in each group.The heart was to dissected weigh the leftventricle in the scales.Results Compared with 3-AB group, the LV end-diastolic diameter(LVEDD)and LV end-diastolic volume(EDV) in the control group were significantly increased (P<0.05), The LV anterior wall end-diastolic diameter(LVAWd), the parameters of LV systolic function(FS) and ejection fraction(EF) were all significantly decreased (P<0.05). The peak radial velocity at the segment of anterior interventricular septum significantly decreased (P<0.05).The peak systolic longitudinal velocity at mitral annulus and segments of left ventricular lateral wall in infarcted group were also significantly decreased (P<0.05). The mean peak systolic velocity at mitral annulus and the peak radial velocity at the segment of anterior interventricular septum both are correlated negtively to pathologic scores(r=-0.92,-0.78,P<0.001).Left vetricular weight measured by ultrasound and those measured by autopsy match well. CONCLUSIONS:Under the conditions of the present experiments,our conclusions are:1. Using quantitative tissue velocity imaging combined with two-dimensional echocardiography, we can assess LV global and regional systolic function after myocardial infarction rats comprehendsively, quantitatively and noninvasively.2. 3-AB has beneficial effects on preventing LV remodeling and improving LV global and regional systolic function after acute myocardial infarction in rats.