Objective To evaluate the effect of smooth muscle cell transplantation on myocardial interstitial reconstruction shortly after myocardial infarction. Methods A total of 48 female Wister rats were randomly divided into two groups with the random number table, the control group (n=24) and the smooth muscle cell transplantation group (n=24). The left coronary artery was ligated to set up the myocardial infarction animal model. An amount of 05 ml phosphate buffered saline(PBS) containing 1×106 smooth muscle cells or 0.5 ml PBS without cells was injected into the injured myocardium immediately. By immunoblot and reverse transcriptionolymerase china reaction (RT-PCR), we observed the amount of protein and mRNA of matrix metalloproteinase2(MMP-2), matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloprotease-3 (TIMP-3) in the myocardium of the rats. Results The transplanted smooth muscle cells survived well. Compared with the control group, myocardial TIMP3 mRNA (1.06±0.22 vs. 0.81±0.19, t=－2.358, P=0.033) and protein content (3.33±0.53 vs. 1.63±0.47, t=－6.802, Plt;0.001) were significantly increased in the transplantation group. Myocardial MMP-2, MMP-9 mRNA (0.49±0.12 vs. 1.16±0.18, t=8.453, Plt;0.001; 0.45±0.12 vs. 0.80±0.11, t=5.884, Plt;0.001) and protein content (3.98±1.08 vs. 6.05±0.91, t=4.139, P=0.001; 0.39±0.14 vs. 0.57±0.17, t=2.409, P=0.031) [CM(1585mm]were significantly reduced in the transplantation group compared with the control group. Conclusion transplanted smooth muscle cells can survive well in the infarction myocardium and can increase the amount of myocardial TIMP-3 mRNA and protein content and reduce myocardial MMP-2, MMP-9 mRNA and protein content, which is an effective way to prevent harmful cardiac remodeling.
ObjectiveTo observe the changes of left atrial geometry before and after mitral valve replacement in patients with different types of mitral valve disease and different heart rhythm, and to identify factors determining left atrial remodeling after mitral valve replacement. MethodsA total of 215 consecutive patients of mitral valve replacement in Department of Thoracic and Cardiovascular Surgery of West China Hospital, Sichuan University from January 2003 to March 2008 were selected and followed up for this study. There were 52 male and 163 female patients with their age of 40.58±10.54 years (ranged, 18-67 years). St. Jude Medical mechanical valves were used. According to the type of mitral valve diseases (mitral stenosis (MS) or mitral regurgitation (MR)) and heart rhythm (atrial fibrillation (AF) or sinus rhythm (SR)), patients were divided into 4 groups. There were 54 patients with MS and SR (including 13 male and 41 female patients with their age of 39.31±9.46 years), 56 patients with MS and AF (including 14 male and 42 female patients with their age of 41.12±10.72 years), 52 patients with MR and SR (including 12 male and 40 female patients with their age of 39.71±10.09 years), 53 patients with MR and AF (including 13 male and 40 female patients with their age of 40.19±11.87 years). All patients had routine examinations and echocardiogram preoperatively and two years after surgery. Left atrial anteroposterior diameter (LAD), left atrial area (LAA), left atrial volume (LAV) and left atrial volume index (LAVi) were used to analyze the changes of left atrial geometry. ResultsThere was no in-hospital death. Major postoperative complications included low cardiac output syndrome in 5 patients, pneumonia in 6 patients. LAVi were lower in mitral stenosis patients than that in mitral regurgitation patients (P<0.05), LAVi were lower in patients with sinus rhythm than that in patients with atrial fibrillation (P<0.05). Two years after mitral valve replacement, the extent of left atrial reverse remodeling were significantly greater in mitral regurgitation patients than in mitral stenosis patients (P<0.05), and the extent of left atrial reverse remodeling were significantly greater in patients with sinus rhythm than that in patients with atrial fibrillation (P<0.05). ConclusionsAge, atrial fibrillation, preoperative left atrial volume, mitral regurgitation, left ventricle end-diastolic diameter are important influencing factors of left atrial reverse remodeling after mitral valve replacement.
ObjectiveTo explore the possibility that GREM1, a bone morphogenetic protein (BMP) antagonist, is a mechanical explanation for BMP signal suppression in congenital heart disease associated pulmonary arterial hypertension (CHD/PAH) patients.MethodsSystemic-to-pulmonary shunt induced PAH was surgically established in rats. At the postoperative 12th week, right heart catheterization and echocardiography evaluation were performed to evaluate hemodynamic indexes and morphology of right heart system. Right heart hypotrophy index and pulmonary vascular remodeling were evaluated. Changes of BMP signal pathway related proteins and GREM1 in lungs and plasma GREM1 concentration were detected. The effect of GREM1 on the proliferation and apoptosis of pulmonary arterial endothelial cells (PAECs) was also explored.ResultsThe hypertensive status was successfully reproduced in rats with systemic-to-pulmonary shunt model. BMP signal pathway was suppressed but GREM1 was up-regulated with no change in hypoxia inducible factor-1 in lungs exposed to systemic-to-pulmonary shunt, while this trend was reversed by systemic-to-pulmonary shunt correction (P<0.05). Immunohistochemical staining demonstrated enhanced staining of GREM1 in remodeled pulmonary arteries. In vitro experiments found that BMP signal was down-regulated but GREM1 expression and secretion were up-regulated in proliferative PAECs (P<0.05). Furthermore, BMP2 significantly inhibited PAECs proliferation and promoted PAECs apoptosis (P<0.05), which could be antagonized by GREM1. In addition, plasma level of GREM1 in rats with systemic-to-pulmonary shunt was also increased and positively correlated with pulmonary hemodynamic indexes.ConclusionSystemic-to-pulmonary shunt induces the up-regulation of GREM1 in lungs, which promotes pulmonary vascular remodeling via antagonizing BMP cascade. These results present a new mechanical explanation for BMP pathway suppression in lungs of CHD/PAH patients.
Lung injury could be classified as acute and chronic injuries, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. Lung function recovery mainly depends on inflammation adjusting, lung and airway remodeling, endogenous stem cell proliferation and differentiation, and tissue repair. The principles of clinical therapy include inhibition of inflammation, balancing coagulation and fibrinolysis, and protective lung ventilation for acute lung injury; while reduction of hyper-secretion, bronchodilation, adjusting airway mucosal inflammation and immunity, as well as improving airway remodeling for chronic obstructive pulmonary disease. The functional recovery of lung and airway depends on endogenous stem cell proliferation and repair. The purpose of clinical treatment is to provide assistance for lung and airway repair besides pathophysiological improvement.
Craniofacial malformation caused by premature fusion of cranial suture of infants has a serious impact on their growth. The purpose of skull remodeling surgery for infants with craniosynostosis is to expand the skull and allow the brain to grow properly. There are no standardized treatments for skull remodeling surgery at the present, and the postoperative effect can be hardly assessed reasonably. Children with sagittal craniosynostosis were selected as the research objects. By analyzing the morphological characteristics of the patients, the point cloud registration of the skull distortion region with the ideal skull model was performed, and a plan of skull cutting and remodeling surgery was generated. A finite element model of the infant skull was used to predict the growth trend after remodeling surgery. Finally, an experimental study of surgery simulation was carried out with a child with a typical sagittal craniosynostosis. The evaluation results showed that the repositioning and stitching of bone plates effectively improved the morphology of the abnormal parts of the skull and had a normal growth trend. The child’s preoperative cephalic index was 65.31%, and became 71.50% after 9 months’ growth simulation. The simulation of the skull remodeling provides a reference for surgical plan design. The skull remodeling approach significantly improves postoperative effect, and it could be extended to the generation of cutting and remodeling plans and postoperative evaluations for treatment on other types of craniosynostosis.
Objective To analyze the clinical effect of partial aortic root remodeling for root reconstruction on Stanford type A aortic dissection. Methods From January 2010 to December 2015, 30 patients (25 males, 5 females) underwent partial aortic root remodeling for root reconstruction on Stanford type A aortic dissection with involvement of aortic root. The range of age was from 27 to 72 years, and the mean age was 51.2±8.0 years. The proximal aortic dissection received partial aortic root remodeling, and the operation procedures included partial aortic root remodeling+ascending aortic replacement in 9 patients, partial aortic root remodeling+ascending aortic replacement+hemi-arch replacement in 6 patients, partial aortic root remodeling+ascending aortic replacement+Sun's procedure in 15 patients. The patients were followed up for 10 to 60 months with a mean of 37.9±3.2 months. Preoperative and postoperative degrees of aortic regurgitation were compared. Results All patients survived from the operation, and one patient died from severe pulmonary infection 15 days after operation. The overall survival rate was 96.7% (29/30). One patient died during the follow-up. Two patients underwent aortic valve replacement in the 12th and 15th postoperative month respectively because of severe aortic regurgitation (AI). Up to the last follow-up, trivial or no aortic regurgitation was demonstrated in 24 patients, but mild aortic regurgitation occurred in 2 patients. Conclusion The surgical treatment for aortic root pathology due to Stanford type A aortic dissection is challenging, and partial aortic root remodeling operations could restore valve durability and function, and obtains the early- and mid-term results.
Objective To evaluate the effectiveness and prospect of nontransplantation surgical cardiac remodeling for endstage cardiac valve disease by performing the remodeling operation (including anatomical and functional remodeling) after strict perioperative adjustment for endstage cardiac valve disease. Methods We retrospectively analyzed the clinical data of 31 patients, including 14 males and 17 females, with endstage cardiac valve disease who were treated with surgical cardiac remodeling operation from December 2005 to July 2009 in the 2nd Hospital of Anhui Medical University . Their age ranged from 27 to 74 years with an average age of 40.4 years. Continuous renal replacement therapy (CRRT) was carried out 3 days before surgery in all patients and intraaortic balloon pumping (IABP) was performed 1-3 days before operation in 9 patients. Among the patients, there were 13 patients of mitral valve replacement (MVR), 7 patients of aortic valve replacement (AVR), 4 patients of tricuspid valve replacement (TVR), and 7 patients of double valve replacement (DVR). At the same time, all patients underwent ventricular or atrial volume reduction operation, including 19 patients of left atrial partial excision or plication, 7 patients of partial left ventricular excision, 5 patients of left atrial and left ventricular volume reduction operation, 21 patients of partial right atrial excision, and 3 patients of partial right ventricular excision. Besides, there were 5 patients of De Vega plasty, 14 patients of annuloplasty and3 patients of coronary artery bypass grafting (CABG). The echocardiogram was used to observe the change of heart function, atrium and ventricular in patients on postoperative and follow -up period. Results After surgery, one patient died of low cardiac output syndrome, and one other patient gave -up because of incision and mediastinum infection after reoperation for hemorrhage. Twentynine patients were followed -up for 3 to 12 months with 1 case lost. During the follow- -up, 3 patients died, of whom 2 died of deterioration of heart function and 1 died of sudden stroke. In the 12th month during the follow -up, heart function of all other 25 patients showed obvious improvements with 12 classⅠ, 7 classⅡ, 3 classⅢ and 3 classⅣ heart function according to NYHA classification. At the end of the follow -up, ejection fraction (5400%±800% vs. 2500%±300%) and cardiac index ［3.30±0.50 L/(min·m2) vs. 1.10±0.30 L/(min·m2)］ were significantly higher than those before operation (P＜0.05), whereas left ventricular end diastolic diameter (5200±1000 mm vs. 9500±1200 mm) and left atrial diameter (3900±800 mm vs. 7000±1200 mm) both decreased significantly than those before operation (P＜0.05). Conclusion Cardiac remodeling operation for endstage cardiac valve disease after active adjustment and preparation can achieve similar results to operation for severe valve diseases, providing a new choice for endstage heart disease.
Atrial fibrillation(AF) is the most common disorder of cardiac rhythm. It has a high morbidity, mortality and disability, and serious impact on quality of life of patients. It is demonstrated that atrial remodeling which includes atrial electrical remodeling and structural remodeling,are the central contributors to the development and selfperpetuating of AF. However, The mechanisms that underlie the atrial remodeling process in AF have not yet been completely elucidated. New strategies for the prevention and termination of AF should build on our knowledge of the mechanisms of atrial remodeling. Medication for the reversal of atrial remodeling may be the new target for the treatment of AF. At present, drugs that target atrial remodeling have already obtained fruitful results in the experimental and clinical investigations. Now some recent advancements of this area is reviewed in this article.
Objective To observe the protective effects of simvastatin at different stages on monocrotaline (MCT) induced pulmonary arteral hypertension (PAH) in rats and evaluate the early preventive effect of simvastatin. Methods Twenty-four male SD rats were randomized into a control group, a PAH group, an early intervention group, and a late intervention group, with 6 rats in each group. The rats in the control group received intraperitoneal injection of normal saline (NS) on d0. The rats in the PAH group received one-off intraperitoneal injection of MCT (50 mg/kg) on d0. The rats in the early intervention group were pretreated with oral gavage of simvastatin (20 mg·kg–1·d–1)(d–7––1) before the intraperitoneal one-off injection of MCT (50 mg/kg, d0) and continued with oral gavage of simvastatin for 14 days (d1~14). The rats in the late intervention group received one-off intraperitoneal injection of MCT (50 mg/kg)(d0) and oral gavage of simvastatin (20 mg·kg–1·d–1) for the next 21 days (d15~35). Thirty-five days after the MCT injection (d36), mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) were measured by right heart catheter. Then the rats were sacrificed for separating the heart and lung, the right ventricular hypertrophy index (RVHI) and percentage of small pulmonary arteries media thickness (WT%), the inflammation score around the small pulmonary arterial were recorded. Results Compared with those in the PAH group, RVSP, mPAP, RVHI and WT% in two simvastatin interventiongroups got much better (P＜0.01), and the inflammation score around the small pulmonary arterial declined (P＜0.05). Compared with those in the late intervention group, RVSP, mPAP in the early intervention group improved (P＜0.05) and WT% decreased more significantly (P＜0.01). However RVHI and the inflammation score around the small pulmonary arterial were not different between two simvastatin intervention groups. Conclusions Both early intervention and late intervention with simvastatin can reduce RVSP, mPAP and WT% in MCT induced PAH rats. Compared with later intervention, early intervention can prevent PAH more remarkably.
Astronauts who are exposed to weightless environment in long-term spaceflight might encounter bone density and mass loss for the mechanical stimulus is smaller than normal value. This study built a three dimensional model of human femur to simulate the remodeling process of human femur during bed rest experiment based on finite element analysis (FEA). The remodeling parameters of this finite element model was validated after comparing experimental and numerical results. Then, the remodeling process of human femur in weightless environment was simulated, and the remodeling function of time was derived. The loading magnitude and loading cycle on human femur during weightless environment were increased to simulate the exercise against bone loss. Simulation results showed that increasing loading magnitude is more effective in diminishing bone loss than increasing loading cycles, which demonstrated that exercise of certain intensity could help resist bone loss during long-term spaceflight. At the end, this study simulated the bone recovery process after spaceflight. It was found that the bone absorption rate is larger than bone formation rate. We advise that astronauts should take exercise during spaceflight to resist bone loss.