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Evaluating Systolic Function Of Post-infarction Heart Failure Rats By Echocardiographic Imaging Technology And The Possible Mechanism Of Ventricular Remodeling Of Post-infarction

Posted on:2011-06-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:W H ZhuFull Text:PDF
GTID:1114360305992750Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Heart failure is a complicated pathophysiologic process, and is a common pathway at the end stage of many diseases. Researches based on heart failure animal models provided abundant information of its mechanism. Rat model become the most common choice of heart failure animal models, for many advantages such as good tolerance to experiment, the similarity in heart anatomy and physiology.The falling of heart function is a very important step in the pathophysiologic process of heart failure. The heart function is the most important index to evaluate the extent of heart failure; its variation can reflect the pharmacological effect of medicine, and make a prognosis of heart failure patient. Echocardiography has its specific advantages in the evaluation of heart function, for it is a convenient, noninvasive and repeatable way. Along with the development of Tissue Doppler Imaging technology, several new technologies emerge and become new methods to evaluate the systolic and diastolic heart function and ventricular remodeling.Ventricular remodeling is the key process in development of congestive heart failure post infarction. Matrix metalloproteinases play an important role in the remodeling of myocardium via degradation of extracellular matrix. Thus, the variation in systolic function and ventricular remodeling of post-infarction heart failure rats are studied in this research in two aspects:ultrasonic research and experimental research. This research provides new thoughts and experimental evidences for the quantitative evaluation of heart function post heart failure. Objective:Apply quantitative tissue velocity imaging (QTVI), tissue tracking imaging (TVI), strain imaging (SI) and strain rate imaging (SRI) to evaluate variation in regional myocardial systolic function quantitatively in post-infarction heart failure rat model. Provide theoretical evidence for researches in heart function post infarction.Methods:70 2-month-old male SD rats (body mass 200-220g) were randomly divided into 4 groups:operation group was divided into 2 groups:4 weeks group and 8 weeks group, including 25 rats in each group。Each group underwent thoracotomy and ligation of anterior descending branch of left coronary artery; sham operation group, including 10 rats, underwent thoracotomy without ligation of coronary artery; control group, including 10 rats, did not receive any treatment. General healthy states of rats were observed every day. Echocardiography technologies, including QTVI, TTI, SI and SRI, were used to evaluate variations in regional systolic function quantitatively in three time point: one day before surgery, the end of the 4th week and the end of 8th week after surgery. Repeatability and variance of all results were analyzed.Result:①Obvious heart failure symptoms were observed in survived rats in operation group about 10 days after surgery.②Compared with control group and sham operation group, fraction shortening (FS) and ejection fraction (EF) decreased significantly in 4 weeks group (P<0.05)and 8 weeks group (P<0.01). FS and EF were significantly lower in the 8 weeks group than 4 weeks group (P<0.05). Left ventricle index (LV) was increased, left ventricle posterior wall index (LVPW) and interventricular septum index (IVS) were decreased in 8 weeks group (P<0.05).③No significant differences in systolic peak velocity (Vs) were found between corresponding segments in control group and sham operation group. Vs in basal, middle, apical segments of anterior and septal wall, middle and apical segments of lateral wall were significantly lower in 4 weeks group than corresponding segments in control group and sham operation group(P<0.05). Vs in basal, middle and apical segments of inferior wall, basal segments of lateral wall were lower in 4 weeks group than that in control group and sham operation group, but there were no significances(P>0.05). Vs in all segments of left ventricle were significantly lower in 8 weeks group than corresponding segments in 4 weeks group(P<0.05).④No significant differences in systolic peak displacement (Ds) were found between corresponding segments in control group and sham operation group. Ds in basal, middle segments of anterior and septal wall were significantly lower in 4 weeks group than corresponding segments in control group and sham operation group(P<0.05). Ds in basal, middle segments of inferior and lateral wall were lower in 4 weeks group than corresponding segments in control group and sham operation group, but there were no significances(P>0.05). Ds in all segments of left ventricle were significantly lower in 8 weeks group than corresponding segments in 4 weeks group(P<0.05).⑤Except for basal and middle segments of inferior wall, peak of strain in systolic(Ssys), peak of strain rate in systolic(SRsys) and strain in end systolic in all segments in operation group were significantly lower than corresponding segments in control group and sham operation group(P<0.05). These three indexes in basal and middle segments of anterior wall, basal segments of lateral wall were significantly lower in 8 weeks group than corresponding segments in 4 weeks group(P<0.05). Except for middle and basal segments of inferior wall, post-systolic strain index (PSI) in all segments in operation group were significantly higher than corresponding segments in control group and sham operation group (P<0.05). PSI in basal, middle segments of anterior wall, basal lateral wall in 8 weeks group were significantly higher than corresponding segments in 4 weeks group(P<0.05).⑥Variances in all indexes within researchers or between researchers were lower than 20%.Conclusion:Post-infarction heart failure rat model can successfully be formed by ligation of descending branch of left coronary artery. Echocardiography technologies such as QTVI, TTI, SI and SRI, in different aspects, can evaluate the variation of regional myocardial systolic function quantitatively in long-axis of the left ventricle in post-infarction heart failure rat model; also, it can reflect the extent of ventricular remodeling. The repeatability of these technologies is well. Objective:Observe the variation in myocardium morphology and collagen volume fraction (CVF) in post-infarction heart failure rats. Detect MMP-2, MMP-9 expression in each group in protein level and mRNA level. Explore the relationship between MMP expression and the progression in myocardium remodeling in post-infarction heart failure rats.Methods:Experimental animals and their groups were the same as research in part one. General health states of rats were observed everyday. Rats were killed at the end of 4 weeks and at the end of 8 weeks. Myocardium tissues were stained by HE and Masson stain, myocardium morphology was observed under microscope and collagen volume fraction was measured. MMP-2 and MMP-9 protein expression in each group were analyzed by Western blot, and their mRNA expressions were analyzed by RT-PCR.Result:①. Obvious heart failure symptoms were observed in survived rats in operation group about 10 days after surgery.②. Compared with rats in control group and sham operation group, Total heart mass index (THMI) and left ventricular mass index (LVMI) in 4 weeks group and 8 weeks group were significantly increased(P<0.05). THMI and LVMI in 8 weeks group were higher than 4 weeks group (P<0.05).③. Compared with rats in control group and sham operation group, severe myocardium fibrosis was found under microscope in operation groups, especially in 8 weeks group.④. Compared with rats in control group and sham operation group, CVF in 4 weeks group and 8 weeks group were significantly increased(P<0.05). CVF in 8 weeks group were higher than in 4 weeks group (P<0.05).⑤. Only few MMP-2 and MMP-9 expression were detected in control group and sham group. MMP-2 and MMP-9 expression in protein level and mRNA level were higher in 4 weeks group and 8 weeks group than in control group and sham operation group. MMP-9 expression in protein and mRNA level was higher in 8 weeks group than 4 weeks group, in contrary, MMP-2 expression was lower in 8 weeks group than 4 weeks group.Conclusion:Along with the progression of heart failure post infarction in 8 weeks after operation, collagen over accumulation, increased myocardium stiffness, dilated ventricle and gradually deteriorated heart function were detected in operation groups. MMP-2 and MMP-9 expression were up regulated in myocardium in protein level and mRNA level, both MMP-2 and MMP-9 took part in the progression of ventricular remodeling.
Keywords/Search Tags:Quantitative tissue velocity imaging, Tissue tracking imaging, Strain and strain rate, Myocardial infarction, Myocardial infarction, Left ventricular mass index, Total heart mass index, Collagen volume fraction, Matrix metalloproteinase
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