Font Size: a A A

Omentopexy Combined With Autologous Atrial Tissue Patch Cardiomyoplasty Improves Cardiac Performance Of Rats With Chronic Myocardial Infarction

Posted on:2012-01-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:C W ZhangFull Text:PDF
GTID:1114330335981907Subject:Cardiovascular surgery
Abstract/Summary:PDF Full Text Request
Objectives:Regional application of tissue engineered cardiac patch can alleviate ventricular remodeling and improve functional recovery in experimental models of ischemia. However, the size of the engineered patch is limited due to the insufficient vascularization. The present study evaluated the effects of autologous atrial tissue patch cardiomyoplasty and/or omentopexy in rat models of myocardial infarction (MI).Methods:Myocardial infarction was induced by left coronary artery ligation in Sprague-Dawley rats. The qualified animals would be allocated randomizedly to four groups three weeks post operatively. The animals in control group only received re-thoracotomy. The autologous atrial tissue patch was harvested from the left atrial appendage along its long axis and was transplanted to the infracted zone in autologous atrial tissue patch cardiomyoplasty group. The omentum was transplanted to the same zone through the diaphragm. In the combined group, these two procedures were completed. The echocardiogram (UCG) was used to evaluate the cardiac remodeling and heart function. The infracted size and scar thickness were assessed by histological study. The angiogenesis and survival of the transplanted atrial tissue were estimated by the immunohistochemistry. Western blot was employed to evaluate the expression of VEGF, MMPs and TIMP3. The activities of MMPs were identified by gelatin zymography. Programmed electrical stimulation was utilized to assess the susceptibility of arrhythmia.Results:After 4 weeks, surviving myocardium was only visualized in the OA group as indicated by immunolabeling cardiac troponin-I. Histological study showed that the infracted size did not decreased in any treatment group while the scar thickness was increased in OA group compared with Con group (391±31μm vs 329±33μm, P<0.05). Only the animals in OA group showed improved heart function assessed by LVEF (57.9±5.8%vs 47.5±4.5%, P<0.05) and LVFS (25.2±3.6%vs 20.7±2.0%, P<0.05). The immunohistochemistry study demonstrated the angiogenesis was improved in the group O and OA (49/0.2mm2 vs 33/0.2mm2, P< 0.01 and 48/0.2mm2 vs 33/0.2mm2, P< 0.01) companied by increased expression of VEGF by western blot. Western blot revealed the expression of MMPs decreased significantly in the OA group while the TIMP3 did not change. The activities of MMP2 and MMP9 were decreased by 68% and 64% respectively by gelatin zymography. The ELISA showed the endothelin-1 level in group O and OA decreased significantly (4.69±0.47 pg/mg vs 5.95±0.55 pg/mg, P<0.01 and 4.79±0.57 pg/mg vs 5.95±0.55 pg/mg; P<0.05). The programmed electrical stimulation demonstrated the arrhythmia score in group O and OA decreased significantly (0.46±0.31vs2.10±0.60, P<0.05 and 0.50±0.34 vs 2.10±0.60, P<0.05).Conclusions:The omentopexy supported the survival of transplanted autologous atrial tissue patch, which resulted in attenuated ventricular remodeling and restoration of heart function in rats with experimental MI. In addition, the omentopexy and combined surgery could decrease the susceptibility of arrhythmia. Our findings might represent a novel therapeutic strategy for heart failure after myocardial infarction. Objectives:The cardiac nerve remodeling plays a key role in the ventricular arrhythmia after myocardial infarction. Our previous research has indicated that the omentopexy could decrease the susceptibility of the ventricular arrhythmia in rats with chronic myocardial infarction. This study aimed to test the hypothesis that this benefit effect is partly attributed to the attenuation of the cardiac nerve remodeling.Methods:The Sprague-Dawley rats were allocated randomizedly to three groups:the sham group without myocardial infarction or omentopexy; the isolated myocardial infarction group without omentopexy and the omentopexy group. Four weeks after the operation, the electrophysiological characteristics were assessed by the electrophysiological techniques. The new and sympathetic nerves in the border zone were analyzed by immunohistochemistry. The expressions of NGF and Connexin43 were manifestated by western blot. The ELISA was utilized to evaluate the expression of the ET-1 of the cardiac tissue.Results:After four weeks, the arrhythmia score of the rats in omentopexy group was significantly less than those in isolated myocardial infarction group(0.9±0.2 vs 3.5±1.2, p<0.05). Meanwhile, the electrical transduction improved significantly in the omentopexy group compared with isolated myocardial infarction group (spontaneous signal ampti tude:3.4±0.3mv vs 1.5±0.2mv,p<0.05; capture threshold:2.2±0.2mv vs 5.5±0.3mv,p<0.05). The immunihistochemisty staining by GAP43 and TH showed that densities of the new and sympathetic nerves decreased remarkably in the omentopexy group (GAP43:768.6±144.1μm2/mm2 vs 1388.4±244.9μm2/mm2, p<0.05; TH:1018.5.±124.7μm2/mm2 vs 1552.4±270.3μm2/mm2, p<0.05). The western blot showed that the expression level of NGF was down-regulated while that of Connexin43 was up-regulated. The ELISA study demonstrated the expression of ET-1 decreased significantly (4.5±0.3pg/mg vs 5.8±0.4 pg/mg,p<0.05).Conclusions:The omentopexy could decrease the susceptibility of ventricular arrhythmia after myocardial infarction by attenuation of the cardiac nerve remodeling. The ET-1-NGF pathway may play a key role in this beneficial effect. Objectives:The risk evaluation model possesses great importance for the cardiac surgeons and the administrative department of health. Our previous research has convinced that the European System of Cardiac Operative Risk Evaluation (EuroSCORE) overestimated the risk of Chinese patients with coronary artery bypass grafting(CABG) and we constructed the Sino System of Coronary Operative Risk Evaluation (SinoSCORE) based on the data from Chinese Coronary Artery Bypass Grafting Registry. This study aimed to compare the predictive values of SinoSCORE and EuroSCORE in the patients undergone isolated off-pump coronary artery bypass grafting (OPCAB) in Fuwai hospital.Method:The clinical data of 1966 consecutive patients undergone isolated OPCAB in Fuwai hospital between Jan.2004 and Dec.2008 was retrospectively collected. The endpoint event was defined as the in-hospital mortality. The score values of all patients were calculated according to the SinoSCORE and EuroSCORE additive model respectively. The areas under the receiver operator curves (ROC) were computed to evaluate the two models'discriminatory ability in predicting in-hospital mortality. The univariate logistic regression and Hosmer-Lemeshow (HL) chi-square test was utilized to assess the calibration of the two models.Results:The mean age of all patients was 61.6±9.3 years and 80.5% were male. Mean SinoSCORE and EuroSCORE of the 1966 patients were 1.6±3.7 and 2.9±2.2 with an observed mortality of 1.1%. The areas under the ROC curves for SinoSCORE and EuroSCORE were 0.76 (95%CI 0.66 to 0.87,P<0.01) and 0.68 (95%CI 0.52 to 0.84,.P<0.05). P values of the HL chi-square test were 0.80 and 0.63, respectively.Conclusions:The present single center study demonstrated that the SinoSCORE is superior to EuroSCORE in predicting the in-hospital mortality in patients undergoing isolated OPCAB. SinoSCORE is an accurate and objective risk stratification model for Chinese OPCAB patients.
Keywords/Search Tags:Myocardial infarction, heart failure, arrhythmia, omentom transplantation, Omentopexy, myocardial infarction, nerve remodeling, off-pump coronary artery bypass grafting, risk evaluation model, European System of, Cardiac Operative Risk Evaluation
PDF Full Text Request
Related items