Objective To explore the role of thrombus precursor protein(TPP) in the monitoring of anticoagulation in the patients with atrial fibrillation (Af) after mechanical heart valve replacement, and suggest the reasonable anticoagulant range. Methods Ninety patients were divided into Af group (n=45), sinus rhythm group (SR group, n=45), and control group (20 patients with non-valvular heart diseases), according to whether Af exist after mitral valve replacement. TPP concentrations and International Normalized Ratio(INR) in the anticoagulant patients were analyzed. Results In patients after mechanical mitral valve replacement, plasma TPP concentrations in both SR group and Af group were lower than that in control group (Plt;0.05,0.01), their INR value were higher than that in control group (Plt;0.01), and Af group had higher plasma TPP concentrations than that in SR group((Plt;)0.05). It was found that there existed contradictions between INR and plasma TPP concentrations in Af group. There were 28 patients with plasma TPP concentrations below 6 μg/ml and without spontaneous bleeding complications in the group with Af, who might be at the optimal anticoagulant status. Their 95% confidence of INR value was 1.90-2.30 and their plasma TPP concentration was 4.29±0.75μg/ml. Conclusion Patients with Af after mechanical heart valve replacement might have higher risk of thromboembolism, INR between 1.90 - 2.30 and plasma TPP concentration between 2.84-6.00 μg/ml might be the optimal anticoagulant therapeutic range.
OBJECTIVE: To explore the possibility of detergent acellularized porcine heart valve serving as a scaffold for tissue engineering valve. METHODS: The porcine aortic valves were acellularized by use of trypsin-EDTA. Triton X-100, RNase and DNase treatment. Biomechanical characteristics of fresh valves and acellularized valve were tested; also fresh valves, acellularized valve and valves treated with method of bioprothetic treatment were implanted subcutaneously in rats; frequently seeded with bovine aortic endothelial cells(BAECs), and then cultured for 7 days. RESULTS: The acellularization procedure resulted in complete removal of the cellular components while the construction of matrix was maintained. The matrix could be successfully seeded with in vitro expanded BAECs, which formed a continuous monolayer on the surface. There is no significant difference of PGI2 secretion of BAECs between cells seeded onto the acellular leaflets and that onto the wells of 24-wells plate (P gt; 0.05). CONCLUSION: Acellularied porcine aortic valve can be applied as a scaffold to develop tissue engineering heart valve.
Abstract: Objective Using Amplex red fluorometric assay to detect the lysyl oxidase (LOX) enzyme activity in tissue engineered heart valve (TEHV). Methods Porcine aortic valves were decellularized with trypsin+ethylene diaminetetraacetic acid(EDTA), TritonX-100, and RNaseⅠ＋DNaseⅠ, then they were seeded by myo-fibroblasts that harvested from rats. Then they were fed with Dulbecco’s modified Eagle medium (DMEM) which contained high glucose for 27 days, they were fed with phenol red-free and serumfree DMEM for 24 hours, and the medium was harvested and used for LOX enzyme activity assays with the Amplex red fluorometric assay. And reverse transcription-polymerase chain reaction (RT-PCR) technique was used to analyze the expression of LOXmRNA in TEHV. Results All the samples produced measurable amounts of active LOX enzyme. The fluorescence units were 45.60±1.66, and the corresponding concentration of LOX enzyme were 0.123±0.003μg/ml. At the same time, all the samples expressed LOXmRNA. The expression of LOXmRNA was corresponding to the results of the Amplex red fluorometric assay. Conclusion It is feasible to detect the LOX enzyme activity in TEHV with the Amplex red fluorometric assay. And this assay gives a way to reflect that LOX plays an important role in collagen cross-linking of extracellar matrix in TEHV.
Based on the analysis of the influence of the valve pivot distance on the performance of mechanical heart valve (MHV), such as the valve opening and closing features, flow field characteristics and the valve assembly properties, value constraints of the valve pivot distance were established, and the reasonable valve was obtained by means of the finite element method. It can be shown that the central flow characteristics of the valve could be enhanced with the increasing of the ratio of pivot distance to valve inner diameter, but the plastic deformation of the ring could be liable to occur in the MHV assembly process. It is proved that the valve of specifications can be designed in similar ratio of pivot distance to valve inner diameter according to the result of the valve performance experiment.
Objective To develop a tissue engineering scaffold by using 4arm branched polyethylene glycol-VS (PEG-VS) crosslinked with decellularized valved conduits (DVC), and to research on its mechanical and biological functions. Methods The valved aortic conduits of rabbits were taken and decellularized by trypsin method and then were crosslinked with 4arm branched PEG-VS to construct the composite scaffolds (CS). The functions of decellularized valved conduits and the composite scaffolds were tested by mechanics test system. Thirty New Zealand white rabbits were equally and randomly assigned to one of the three groups: the control group, the DVC group, and the CS group. Valved aortic conduits, decellularized valved conduits and composite scaffoldswere transplanted into the common carotid artery of the abovementioned three groups of rabbits respectively. Twentyeight days after the operation, patency of the transplants was tested by Color Doppler ultrasound; micromorphology and inflammatory infiltration were observed by hematoxylin eosin（HE） staining andscanning electron microscope (SEM)，and endothelialization of composite scaffolds was detected by immunofluorescent staining. Results A series of biomechanical analyses revealed that the composite scaffolds had highly similar mechanical properties as fresh tissue, and had superior elastic modulus (P=3.1×10-9) and tensile strength (P=1.1×10-6) compared with decellularized valved conduits. Color Doppler ultrasound revealed that the graft patency for the CS group was better than the control group (P=0.054) and the DVC group (P=0.019), and the intraaortic thrombosis rate and distortion rate decreased significantly. HE staining and SEM showed that the endothelialization of composite scaffolds in the CS group was significantly higher than the other two groups with the endothelial cells evenly distributed on the scaffolds. The [CM(159mm]immunofluorescent staining indicated that the positive rate of the endothelial cell marker CD34 was higher than the other two groups. Conclusion The composite scaffolds using 4arm branched PEGVS crosslinked with DVC have great mechanical and biological properties.
Objective To observe whether Cyclo-RGDfK (Arg-Gly-Asp-D-Phe-Lys) could enhance the adhesion of myofibroblast to decellularized scaffolds and upregulate the expression of Integrin αVβ3 gene. Methods Myofibroblast from the rat thoracic aorta was acquired by primary cell culture. The expression of Vimentin and α-smooth muscle actin(α-SMA) has been detected by immunoflurescent labeling. Decellularized valves have been randomly divided into three groups (each n=7). Group A (blank control): valves do not receive any pretreatment; Group B: valves reacted with linking agent NEthylN(3dimethylaminopropyl)carbodiimide hydrochloride (EDC) for 36 hours before being seeded; Experimental group: Cyclo-RGD peptide has been covalently immobilized onto the surface of scaffolds by linking agent EDC. The fifth generation of myofibroblast has been planted on the scaffolds of each group. The adhesion of myofibroblast to the scaffolds was evaluated by HE staining and electron scanning microscope. The expression of Integrin αVβ3 was quantified by halfquantitative reverse transcriptionpolymerase china reaction (RT-PCR). Results We can see that myofibroblast has exhibited b positive staining for Vimentin and α-SMA. Besides, it has been shown that the expression of Integrin αVβ3 was much higher in the experimental group than that of the group A and group B(Plt;0.05). There was no statistically difference in group A and group B (P=0.900). Conclusion RGD pretreatment does enhance the adhesive efficiency of seeding cells to the scaffolds and this effect may be related to the upregulation of Integrin αVβ3.
The management of women with mechanical heart valves during pregnancy remains difficult and controversial. The selection of prosthetic heart valve, management during pregnancy and delivery period, guidelines and anticoagulation strategy used in patients with a mechanical heart valve in China are summarized in this review.
Abstract: Objective To investigate the anticoagulation effect of warfarin on pregnant women with prosthetic mechanical heart valves during the whole course of pregnancy and their fetuses. Methods Followup survey was carried out on 103 pregnant women with prosthetic mechanical heart valves treated in the Second Xiangya Hospital of Central South University from April 1998 to June 2010. Their age ranged from 19 and 38 years (26.4±3.8 years). All the 103 pregnant women were given oral administration of warfarin during the whole course of pregnancy. The average dose of domestic warfarin was 3.30±0.43 mg/d (87 cases), while the average dose of imported warfarin was 2.90±1.05 mg/d (16 cases). Results None of the patients suffered from serious embolic events. One patient suffered from spontaneous peritoneal hemorrhage. There were 4 cases of intrauterine deaths, and 5 cases of fetal malformation including 1 case of Down’s syndrome and 4 cases of hydrocephalus. Six cases of low birth weight infants and 1 case of ABO hemolytic disease were also found. All the other neonates were healthy with normal weight. No pregnant women suffered from postpartum hemorrhage. Conclusion Oral administration of low dose warfarin (lt;5 mg/d) during the whole course of pregnancy is a relative safe and effective anticoagulation protocol.
Objective To investigate the role of clinical pharmacists in warfarin therapy. Methods A total of 134 patients underwent prosthetic heart valve replacement and had warfarin for life from March 2013 to October 2013 in Fujian Medical University Union Hospital. All patients were equally divided into two groups (an intervention and a non-intervention group) crosswise by sequence. There were 67 patients in each group. The anticoagulant effects of the two groups were compared. Results There was no statistical difference in the patients' demographic information between the two groups. However, the time for the patients to reach the target international normalized ratio(INR) values for the first time (7.1±3.3 dvs. 10.5±5.0 d,P=0.000) and time of INR in the therapy range (46.3%±18.8%vs.19.0%±16.2%,P=0.000) during their hospitalization, proportion of time of under anticoagulation (47.5%±19.5%vs. 71.2%±22.9%,P=0.000), proportion of time of anticoagulation overdose (5.3%±8.2%vs. 9.9%±16.7%,P=0.002) were significantly different. While there was no statistical difference in postoperative hospitalization time between the two groups (19.9±6.6 dvs. 18.1±7.0 d,P=0.137). There were 4 patients (6.0%) with minor hemorrhage and no severe complication was found in the intervention group. There were seven patients (10.4%) with mild hemorrhage, two patients with stroke, one patient with mild pulmonary embolism, and severe complication rate of 4.5% in the non-intervention group. Conclusion With clinical pharmacists involved in the whole anticoagulation therapy progress of patients after mechanical heart valve replacement, the time to achieve the therapeutic window for the first time is effectively shorten, and the time of the INR value controlled in therapeutic range is highly improved during hospitalization time. Moreover, the patients' risk of thrombosis and bleeding is eventually reduced.
In recent years, the field of transcatheter heart valve interventional therapy has developed rapidly. Valvular thrombosis is a rare postoperative complication, which can affect valvular function early or lead to clinical embolic events, and is gradually being valued by surgeons. The clinical manifestations of thrombosis after different types of interventional valve replacement are different. Although anticoagulant therapy is believed to be effective for valve thrombosis, the selection of anticoagulant drugs and the duration of anticoagulation are still controversial. This article reviews the definition, clinical features, prevention and treatment of valve thrombosis after several types of transcatheter heart valve replacement, mainly related to transcatheter aortic valve replacement and transcatheter mitral valve replacement, and aims to provide a reference for the diagnosis and treatment of valve thrombosis after transcatheter heart valve replacement.