As a new discipline, the cardiac surgery has a great development in the modern age, but still faces many problems and disputes. The emergence of the evidence-based medicine(EBM),which emphasizes the best evidence, and combines the doctor’s clinical experience to make the best judgment, gives the development of the cardiac surgery a new thinking . Four systematic reviews published in The Cochrane Library (Issue 3, 2004) have interprated the importance of EBM on how to resolve the actual problems in different field of the cardiac surgery.
Objective To explore the feasibility of tissue-engineered heart valve （TEHV） reconstructed on acellularized porcine aortic valve and rabbit bone marrow stromal cells （BMSCs） in vitro. Methods Acellularized was performed in porcine aortic valve by the detergent and enzymatic extraction process . Morphological and biomechanical properties were compared between the decellularized scaffolds and the fresh valves. Rabbit BMSCs were seeded on the scaffolds. The TEHV were analyzed by light microscopy, electron microscopy and immunohistochemistry. Results Almost complete removal of the cellular components and soluble protein of valves were observed , while the construction of matrix was properly maintained. Biomechanical tests demonstrated no statistically significant change in the breaking intensity （642 ± 102 g/mm2 vs. 636 ± 127g/mm2） and breaking extensibility （62. 2%± 18. 1% vs. 54. 4%±16. 0%） in the porcine values before and after decellularization. Subsequent seeding with rabbit BMSCs on the matrix was so successful that the surface of the scaffold had been covered with a continuous monolayer cells through light microscopy and electron microscopy. Positive of α-smooth muscle actin and negative of CD31 were observed after rabbit BMSCs seeded on the matrix through immunohistochemistry. Conclusion It is feasible to reconstruct TEHV in vitro on acellularized porcine aortic valve scaffold and rabbit BMSCs.
Objective To introduce a new type of bileaflet mechanical prosthetic heart valve （GK bileaflet valve）and evaluate clinically the early hemodynamic effect and short term follow-up after its replacement. Methods Sixty-one patients with heart valve diseases were operated upon. The mitral valve replacement was performed in 34 patients, aortic valve replacement in 16 patients and double valve replacement in 11 patients. A total of 72 GK bileaflet mechanical valves were implanted, 45 in mitral position, and 27 in aortic position. Blood consistency and hemodynamics were monitored. Follow-up was carried out routinely to check whether there were some valve-related complications. Results There was no early mortality （〈30 d）. Only one patient died of trauma 2 months after the operation. Follow-up was 100% and extended 1 to 2. 5 years. Without valve-related complications all patients had lived for more than 1 to 2.5 years. In 98% （60/61） of survivors heart functional performance had improved to New York Heart Association class Ⅰ or Ⅱ . Conclusion Early clinical results and short term follow up demonstrate that GK bileaflet prosthetic heart valve exhibits excellent hemodynamic properties, satisfied blood consistency and a low incidence of valve-related complications. Midterm and long-term results should be observed further.
The engineered heart tissues (EHTs) is regarded as a hope for myocardial repair and regeneration. But a series of " bottleneck” problems, such as vascularization, hinder their clinical translation. This review focuses on the strategies to vascularization of EHTs and encourages the emergence of novel EHTs that can meet clinic requirement properly.
With the development of molecular and cellar cardiology, gene therapy to cardiovascular disease has become the hot spot and the direction of study. Now, preclinical studies on ultrasound-mediated gene delivery (UMGD) in cardiovascular disease have achieved some success, but it is still hindered by a series of practical challenges for clinical translation. Even so, UMGD still holds the promise to cardiovascular disease in gene therapy for its non-invasiveness, accuracy, safety and ability to deliver multiple genes with repeated deliveries. In this review, we will focus on the basic principle, the current development, the future prospect and drawbacks of UMGD in the therapeutic applications of cardiovascular disease.
ObjectiveTo construct a cationic microbubble (CMB), and investigate the enhancement of gene transfection efficiency and therapeutic effect of ultrasound-targeted microbubble destruction (UTMD) in vivo with CMB compared to definity MB (DMB).Methods In vitro, the CMB was prepared by the method of thin film hydration. The morphology, size, zeta potential, and gene-carrying capacity of CMB were compared with the DMB. In vivo, the firefly luciferase gene which was used as a reporter gene was targeted transfected into myocardium of 16 rats with CMB and DMB, respectively. The gene transfection efficiency and targeting were observed dynamically. Then, ischemia-reperfusion (I/R) model was performed on 64 rats. The models of 60 rats were successfully confirmed by using ultrasonography at 5 days after I/R. The rats were divided into 3 groups (n=20) randomly. The control group received DMB carrying empty plasmid for transfection; DMB group received DMB carrying AKT plasmid for transfection; and CMB group received CMB carrying AKT plasmid for transfection. The cardiac perfusion, cardiac function, infarct size, and infarct thickness were measured by ultrasonography and histological observations after treatment. In addition, the capillary and arteriolar densities were measured with immunohistochemical staining. The myocyte apoptosis was measured with TUNEL staining. The protein expressions of AKT, phospho-AKT (P-AKT), Survivin, and phospho-BAD (P-BAD) were measured by Western blot.ResultsThe size of CMB was uniformly. The zeta potential of CMB was significantly higher than that of DMB (t=28.680, P=0.000). The CMB bound more plasmid DNA than the DMB (P<0.05). The luciferase activity of myocardium were higher in CMB group than in DMB group bothin vitro and in vivo measurements (P<0.05). There was no significant difference between groups in the ratio of signal intensity in anterior wall to posterior wall, ejection fraction (EF), and fractional shortening (FS) at 5 days after I/R (P>0.05), but the above indexes were significant higher in CMB and DMB groups than in control group at 21 days after I/R (P<0.05). Besides, the above indexes were significant higher in CMB group than in DMB group at 21 days after I/R (P<0.05). The infarct size was the smallest and infarct thickness was the thickest in the CMB group, followed by DMB group, control group at 21 days after I/R. The capillary and arteriolar densities of CMB and DMB groups were significant higher than those of control group at 21 days after I/R (P<0.05). Besides, the capillary and arteriolar densities of CMB group were significant higher than those of DMB group (P<0.05). The apoptotic cells were the most in the control group, followed by DMB group, CMB group at 3 days after gene transfection, showing significant differences between groups (P<0.05). The protein expressions of AKT, P-AKT, Survivin, and P-BAD were significant higher in CMB and DMB groups than those in control group at 3 days after gene transfection (P<0.05). Besides, these protein expressions were significant higher in CMB group than those in DMB group (P<0.05).ConclusionThe DNA-carrying capacity and gene transfection efficiency are elevated by CMB, although its physicochemical property is the same as DMB. When ultrasound-targeted AKT gene transfection is used to treat myocardial I/R injury in rats, delivery of AKT with the CMB can result in higher transfection efficiency and greater cardiac functional improvements compared to the DMB.
ObjectiveTo investigate the feasibility of animal model of the reconstruction of right ventricular outflow tract in rats.MethodsA total of 15 female Sprague-Dawley (SD) rats underwent right ventricular outflow tract reconstruction surgery. Before the operation, the collagen scaffolds were treated with g 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride chemistry (EDC), and seeded with human bone marrow stem cells (h-MSCs). Three days after the surgery, 3 rats were randomly sacrificed to evaluate the transmural resection of right ventricular outflow tract. One or 3 months later, other 3 rats at each timepoint were sacrificed, stained with Masson’s Trichrome to observe the degradation of scaffold. Furthermore, 4 weeks after the surgery, 4 rats were sacrificed and the hearts were sliced. Anti-human mitochondria staining was used to identify the survival of seeding cells.ResultsThe transmural resection of right ventricular outflow tract was feasible in rats at an acceptable mortality (13.3%). After EDC treatment, the degradation rate of collagen scaffold was extended greatly. The seeding cells were detected by anti-mitochandria immunofluorescent staining in all patches 4 weeks after the operation.ConclusionRat model of right ventricular outflow tract reconstruction could be a stable, reliable and economical screening model for engineered heart tissue research.