The Application and Teaching Value of a Ventricular Septal Defect Canine Model Established by Transcatheter Puncture.

This study aimed to improve and further explore a ventricular septal defect (VSD) canine model on the basis of the transcatheter puncture method and to evaluate its application and teaching value.In order to lessen the complications of VSD closure, it is necessary to improve the currently available treatment devices using appropriate animal models.In this study, we used 16 healthy adult canines as our models. After anesthesia, the VSD puncture was performed, followed by balloon dilatation of the perforation. VSD was confirmed by angiography. The venous-artery orbit was established, and the VSD was then closed once the catheter and occluder were across the defect.Of the experimental canines, 14 of the 16 canines were successfully modeled, giving a success rate of 87.5%. The canines underwent an immediate creation of a venous-artery orbit for teaching practice and were implanted with an occluder during the procedure. After 4 weeks, 13 canines survived. As per our findings, most VSD types established by the puncture were perimembranous (10 of 13, 77%).The current model has a high success rate. The model can not only avoid the risk of infection and hemodynamic disorders associated with an open thoracotomy, but can also be effectively used in evaluating the impact of occluders. It can also directly measure the parameters of the devices during the procedure, thus having a very high experimental and teaching value.

Percutaneous occlusion of transseptal puncture-related free wall perforation at the coronary sinus with a ventricular septal occluder during left atrial appendage closure: A case report.

Coronary sinus perforation is a life-threatening complication of transseptal puncture and needs to be repaired immediately. In this study, we report a case of a 74-year-old female patient with nonvalvular atrial fibrillation, who is a poor long-term anticoagulation candidate. During the manipulation of transseptal puncture, a perforation of the free right atrial wall at the coronary sinus ostium occurred, which was caused by the Brockenbrough needle and followed by the immediate advancement of an 8.5-French transseptal sheath. In consideration of the danger of cardiac tamponade after sheath removal, we decided to leave the 8.5-French sheath in the pericardial cavity. Then, we advanced a 6 mm ventricular septal occluder through the sheath. Finally, we achieved successful deployment of the device and closure of the perforation under the guidance of fluoroscopy and transthoracic echocardiography. Subsequently, the left atrial appendage orifice was occluded with a 21 mm Watchman device. This case illustrates that percutaneous device closure is feasible for inadvertent perforation of the free right atrial wall at the coronary sinus during transseptal puncture and should be considered as an alternative to surgery.

Plasma miR-451 with echocardiography serves as a diagnostic reference for pulmonary hypertension.

Due to the lack of typical clinical symptoms, the average delay time for diagnosis of pulmonary hypertension (PH) is longer than 2 years. It is urgent to find biomarkers for PH diagnosis. In this study we investigated whether plasma microRNAs (miRNAs) can be used as biomarkers for PH diagnosis. We used microarray to identify dynamic miRNAs between PH and non-PH patients. The candidate miRNAs were verified using qRT-PCR in a mouse model of PH, which was induced by monocrotaline (MCT) injection. We observed that miR-21, miR-126, miR-145, miR-191 and miR-150 had no differences between control mice and MCT-treated mice; but plasma miR-451 was significantly decreased in the 2wk-MCT group, with no further decrease in the 4wk-MCT group. Plasma miR-451 was also markedly decreased in PH patients, whereas miR-21, miR-126, miR-150 and miR-320 did not show differences between 53 PH patients and 54 non-PH patients. Receiver operating characteristic curves (ROCs) were constructed from the patient data to assess the clinical diagnostic values of circulating miR-451 and Doppler echocardiography (D-ECHO). The areas under the curve (AUCs) of ROCs for miR-451 and D-ECHO were 0.710 and 0.766, respectively. Combination of miR-451 and D-ECHO with AUC of 0.825 was superior to the use of either miR-451 or D-ECHO alone for PH diagnosis. In conclusion, plasma miR-451 has a moderate diagnostic value in PH comparable to that of D-ECHO, and the combination of miR-451 with D-ECHO has better diagnostic value than either method alone, which may have implications for PH diagnosis.

MicroRNA-126a Directs Lymphangiogenesis Through Interacting With Chemokine and Flt4 Signaling in Zebrafish.

OBJECTIVE: MicroRNA-126 (miR-126) is an endothelium-enriched miRNA and functions in vascular integrity and angiogenesis. The application of miRNA as potential biomarker and therapy target has been widely investigated in various pathological processes. However, its role in lymphatic diseases had not been widely explored. We aimed to reveal the role of miR-126 in lymphangiogenesis and the regulatory signaling pathways for potential targets of therapy. APPROACH AND RESULTS: Loss-of-function studies using morpholino oligonucleotides and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system showed that silencing of miR-126a severely affected the formation of parachordal lymphangioblasts and thoracic duct in zebrafish embryos, although their development in miR-126b knockdown embryos was normal. Expression analyses by in situ hybridization and immunofluorescence indicated that miR-126a was expressed in lymphatic vessels, as well as in blood vessels. Time-lapse confocal imaging assay further revealed that knockdown of miR-126a blocked both lymphangiogenic sprouts budding from the posterior cardinal vein and lymphangioblasts extension along horizontal myoseptum. Bioinformatics analysis and in vivo report assay identified that miR-126a upregulated Cxcl12a by targeting its 5' untranslated region. Moreover, loss- and gain-of-function studies revealed that Cxcl12a signaling acted downstream of miR-126a during parachordal lymphangioblast extension, whereby Flt4 signaling acts as a cooperator of miR-126a, allowing it to modulate lymphangiogenic sprout formation. CONCLUSIONS: These findings demonstrate that miR-126a directs lymphatic endothelial cell sprouting and extension by interacting with Cxcl12a-mediated chemokine signaling and Vegfc-Flt4 signal axis. Our results suggest that these key regulators of lymphangiogenesis may be involved in lymphatic pathogenesis of cardiovascular diseases.

Transcatheter Closure of Perimembranous Ventricular Septal Defects Using Dual Wire-Maintaining Technique.

OBJECTIVE: The present study was designed to evaluate the safety and feasibility of transcatheter closure of perimembranous ventricular septal defects (PmVSDs) with dual wire-maintaining technique (DWMT). PATIENTS/METHODS: From January 2010 to December 2013, a total of 241 patients (men: 109, women: 132; mean age: 22.2±15.4 years) with congenital PmVSDs were randomised to either the conventional technique (CT) group (n=118) or the DWMT group (n=123). RESULTS: In the CT group, the track wire was withdrawn before occluder insertion. In the DWMT group, the track wire was maintained in the delivery sheath during the procedure. Both the procedure time and fluoroscope time were reduced significantly in the DWMT group patients who required device replacement compared with CT group patients (median time: 46.0±14.8min vs. 56.0±15.2min, p<0.05; 15.0±11.6min vs. 22.0±10.1min, p<0.05). There was no difference in the incidence of complications between the two groups. CONCLUSION: The DWMT is safe and feasible for transcatheter treatment of PmVSDs, especially in patients requiring device replacement, for it avoids reconstruction of the "arteriovenous wire loop", left ventriculography from the contralateral femoral route, or the use of a larger femoral artery short sheath.

Decreased tricuspid regurgitation following percutaneous closure of congenital perimembranous ventricular septal defect: immediate and 6-month echocardiographic assessment.

As a common concomitant performance and the most frequent complications of transcatheter perimembranous ventricular septal defect (VSD) closure, tricuspid regurgitation (TR) has rarely been concerned. From January 2008 to December 2012, a total of 70 patients (men: 33, women: 37; mean age: 30.0 ± 17.1 years) with at least mild TR before VSD closure were examined in 508 consecutive congenital perimembranous VSD patients to investigate the outcomes of TR. After VSD closure, the jet area decreased from 3.4 ± 2.5 to 1.2 ± 2.5 cm(2) (p < 0.001); however, no significant decrease was found in 3 patients (mean age 59.7 ± 2.5 years) with severe TR (12.0 ± 1.2 versus 11.2 ± 3.2 cm(2), p = 0.668). Compared to the early outcome after VSD closure, the jet area detected by TTE at 6-month follow-up had further decreased (1.2 ± 2.5 versus 0.9 ± 2.2 cm(2), p < 0.001). In 6 patients, a slight residual shunt was detected immediately after VSD closure and diminished in 3 patients at 6-month follow-up. The hemolysis occurred in one of these six patients and recovered after 3 days. In conclusion, functional TR was ameliorated after percutaneous VSD closure, although persistent abundant TR was common in patients with severe TR before procedure.

Symptomatic sinus tachycardia with perpetuating slow pathway: successful treatment with radiofrequency ablation.

We report a case of sinus tachycardia with perpetuating slow pathway (SP) conduction in a 42-year-old woman who developed severe symptoms as a result of atrioventricular (AV) desynchronization. The restoration of an AV synchrony, achieved with selective radiofrequency ablation of the SP, eliminated the symptomatic arrhythmia and may represent a reasonable therapeutic option despite the fact that the patient has no AV-node reentrant tachycardia. This case demonstrates the importance of AV timing.

Comparison of medium-term results of transcatheter correction versus surgical treatment for secundum type atrial septal defect combined with pulmonary valve stenosis.

This study was undertaken to compare the clinical results of traditional surgery and a percutaneous procedure for secundum type atrial septal defect (ASD) combined with pulmonary valve stenosis (PS). A total of 78 consecutive patients were identified between March 2004 and July 2012 in our institution. Thirty-five patients (44.9%) underwent percutaneous correction and the remaining 43 patients (55.1%) were treated surgically. All patients had simultaneous complete correction in both groups and no serious complications occurred. The surgical group was significantly younger (13.9 ± 13.0 versus 31.0 ± 17.5 years, P < 0.001) and had a longer mean hospital stay (12.6 ± 4.7 versus 5.3 ± 1.5 days, P < 0.001). There were no significant differences in defect size (18.0 ± 7.9 versus 16.9 ± 8.4 mm, P = 0.553) and transvalvular gradient detected by transthoracic echocardiography (TTE) (74.7 ± 28.3 versus 87.6 ± 37.8 mmHg, P = 0.089) between the two groups. Significant tricuspid regurgitation (TR) decreased from 66% to 14% in the transcatheter group and from 40% to 9% in the surgical group. Mild pulmonary regurgitation was detected in 8 patients in the transcatheter cohort and in 6 patients in the surgical cohort after the procedure. At last follow-up, 83% and 93% of the patients in the transcatheter and surgical groups, respectively, were free of any symptoms, and a significant improvement from preprocedure was observed in the transcatheter group but not in the surgical group (P = 0.005 and P = 0.062). In conclusion, transcatheter correction is a valuable alternative to surgery and allows more patients to be effectively treated in China.

Simultaneous transcatheter treatment of perimembranous ventricular septal defect and other congenital cardiopathies.

OBJECTIVE: To assess the efficacy and safety of simultaneous transcatheter corrections of perimembranous ventricular septal defect (VSD) and other congenital cardiopathies. PATIENTS/METHODS: From 2004 to 2012, 56 patients (25 male, 31 female), aged 14.2±10.1, with compound congenital cardiovascular abnormalities underwent simultaneous transcatheter interventional procedure. Of the 56 patients, 32 had VSD and atrial septal defects (ASD); 17 had VSD and patent ductus arteriosus (PDA); and seven had VSD and pulmonary valve stenosis (PS). Percutaneous balloon pulmonary valvuloplasty (PBPV) was performed before the closure of VSD, PDA, or ASD. RESULTS: The combined transcatheter interventional procedure was successfully performed in all patients. Among these, two occluders were implanted in each of 49 patients, seven patients with VSD combined with PS underwent successfully balloon valvuloplasty and VSD closure. The size of VSD, ASD and PDA detected by TTE was 4.8±1.7 mm, 9.0±5.0 mm and 4.5±2.5 mm, respectively. The occluder diameter of VSD, ASD and PDA was 7.6±2.2 mm, 14.3±6.2 mm and 7.9±3.2 mm, respectively. The peak-to-peak transpulmonary gradient decreased from 60.4±19.7 mmHg to 15.0±5.0 mmHg (p<0.001) in seven patients with VSD combined with PS. One patient with VSD and ASD had a permanent pacemaker implanted because of third-degree atrioventricular block two months after the procedure. There were not serious adverse events in relation to the combined procedures during the 23.8±20.7 months of follow-up in other 55 patients. CONCLUSION: The simultaneous treatment of VSD and other congenital cardiopathies using transcatheter-based procedures is safe and effective, which can provide satisfactory results.

Development and preclinical evaluation of a biodegradable ventricular septal defect occluder.

OBJECTIVES: This study evaluated the feasibility, effectiveness, and safety of a biodegradable (BD) occluder for closure of ventricular septal defect (VSD) in an acute canine model. BACKGROUND: All current available VSD occluders are permanent implants which consist of a metal framework and synthetic fabrics. However, the septal occluder in vivo plays the role of a temporary bridge that facilitates the ingrowth of fibrous connective tissue and endothelialization. The ideal occluder may be a temporary scaffold which can be gradually absorbed in vivo and replaced by "native" tissue. METHODS: The BD VSD occluder consists of a polydioxanone (PDO) framework and two pieces of poly-L-lactic acid (PLLA) fabrics. Percutaneous transcatheter closure of interventionally created VSDs was performed in 16 dogs using the BD occluders. Follow-up consisted of electrocardiography, transthoracic echocardiography, and fluoroscopy from 1 week to 24 weeks post-implantation. Gross pathology and histopathology were obtained at 6, 12, and 24 weeks follow-up. RESULTS: Implantation of the BD occluders was successful in 15 animals. The devices became well integrated into the ventricular septum with complete endothelialization at 12 weeks after implantation. After 24 weeks in vivo, the PDO framework of devices was largely absorbed and replaced by the ingrowth of collagenous fibers, and the PLLA fabric within disks was partly degraded. Neither occluder dislocation nor VSD recanalization occurred during follow-up. CONCLUSIONS: The BD occluder proved safe and effective for VSD closure. This device is characterized by compatible mechanical properties, a fully BD property, and a good match between the degradation of occluder and the healing response of organism.

Two functional microRNA-126s repress a novel target gene p21-activated kinase 1 to regulate vascular integrity in zebrafish.

RATIONALE: MicroRNAs (miRNAs) are key regulators of vascular development and diseases. The function and underlying mechanism of endothelial miRNAs have not been fully defined. OBJECTIVE: To investigate the role of endothelial miR-126 in zebrafish vascular development. METHODS AND RESULTS: Two homologs of miR-126, miR-126a (namely miR-126 in previous literature) and miR-126b, with only 1 nucleotide difference in their mature sequences, were identified in zebrafish genome. In vitro analysis showed that both precursors could sufficiently produce mature functional miRNAs. Expression analyses by Northern blot and quantitative RT-PCR showed that both miR-126s accumulated significantly 12 hours after fertilization and were specifically expressed in endothelial cells of zebrafish. Inhibition of miR-126a or miR-126b with specific morpholinos caused cranial hemorrhage, and simultaneous inhibition of both miR-126s resulted in a pronounced hemorrhage in higher percentage of embryos. Bioinformatics prediction showed that the targets of miR-126a/b partially overlapped but essentially differed. p21-activated kinase1 (pak1) was identified as a novel target of miR-126a/b, and pak1 3' untranslated region was differently regulated by these 2 miRNAs. Quantitative RT-PCR, in situ hybridization, and Western blot analyses showed that the level of pak1 was reduced when miR-126a/b were overexpressed. Notably, pak1 expression in endothelial cells was increased when miR-126a/b were knocked down. Furthermore, overexpression of the active form of human pak1 caused cranial hemorrhage, and knockdown pak1 effectively rescued the hemorrhage caused by inhibiting miR-126a/b. CONCLUSIONS: Two functional endothelial cell-specific miRNAs, miR-126a and miR-126b, synergistically regulate zebrafish vascular integrity, and pak1 is a critical target of miR-126a/b in vascular development.

Percutaneous valved stent implantation in the ascending aorta for the treatment of very high-risk aortic regurgitation: an animal study.

PURPOSE: We investigated the effects of percutaneous valved stent implantation in the ascending aorta as an alternative treatment for aortic regurgitation in a canine model. MATERIALS AND METHODS: A total of 16 healthy dogs weighing an average of 18.3 ± 2.1 kg were used for the establishment of animal models of chronic aortic regurgitation by percutaneous aortic valve perforation and balloon dilation. At 2 mo after successful model establishment, all experimental animals underwent valved stent implantation in the ascending aorta and then were followed up for 3 mo. RESULTS: Experimental models of chronic aortic regurgitation were successfully established in 10 dogs. Surviving dogs underwent successful valved stent implantation in the ascending aorta and were subsequently followed up for 3 mo. The level of instantaneous aortic regurgitation at 3-mo follow-up was significantly reduced compared with that before valved stent implantation (2.4 ± 0.9 versus 10.6 ± 2.1 mL/s, P < 0.05). The left ventricular ejection fraction was significantly increased (53.8 ± 4.2% versus 37.8 ± 3.7%, P < 0.05), and the left ventricular end-diastolic volume was also significantly reduced (30.3 ± 2.2 versus 40.1 ± 3.6 mL, P < 0.05). No paravalvular leak, stroke, atrioventricular block, or other complications occurred in dogs undergoing valved stent implantation. CONCLUSIONS: Percutaneous valved stent implantation in the ascending aorta is feasible, effective, and safe as an alternative treatment for very high-risk aortic regurgitation in a canine model.

Uracils at nucleotide position 9-11 are required for the rapid turnover of miR-29 family.

MicroRNAs are endogenous small RNA molecules that regulate gene expression. Although the biogenesis of microRNAs and their regulation have been thoroughly elucidated, the degradation of microRNAs has not been fully understood. Here by using the pulse-chase approach, we performed the direct measurement of microRNA lifespan. Five representative microRNAs demonstrated a general feature of relatively long lifespan. However, the decay dynamic varies considerably between these individual microRNAs. Mutation analysis of miR-29b sequence revealed that uracils at nucleotide position 9-11 are required for its rapid decay, in that both specific nucleotides and their position are critical. The effect of uracil-rich element on miR-29b decay dynamic occurs in duplex but not in single strand RNA. Moreover, analysis of published data on microRNA expression profile during development reveals that a substantial subset of microRNAs with the uracil-rich sequence tends to be down-regulated compared to those without the sequence. Among them, Northern blotting shows that miR-29c and fruit fly bantam possess a relatively rapid turnover rate. The effect of uracil-rich sequence on microRNA turnover depends on the sequence context. The present work indicates that microRNAs contain sequence information in the middle region besides the sequence element at both ends.

Attenuation of microRNA-22 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy.

Cardiac hypertrophy, which is characterized by the enlargement of cell size, reactivation of fetal genes, remains one of the most important triggers to heart failure. Increasing evidence shows that microRNA (miRNA) is extensively involved in the pathogenesis of cardiac hypertrophy. But the effects of miRNAs on cardiomyocyte hypertrophy have not been completely solved yet. Here, we showed that a collection of miRNAs was aberrantly expressed in hypertrophic cardiomyocytes induced by phenylephrine (PE) or angiotensin II (Ang II). Among them, miR-22 was the most strikingly up-regulated miRNA. To investigate the role of miR-22 in hypertrophy, both over-expression and knock-down assays were performed on cardiomyocytes. The results showed that up-regulation of miR-22 significantly increased the cell size and markedly influenced the expression of hypertrophic markers, including induction of nppa and reduction of myh6. In contrast, reduction of miR-22 level attenuated either PE- or Ang II-induced hypertrophic reaction. Furthermore, several genes, including PTEN, were identified as potential targets of miR-22 by bioinformatic algorithms. Using luciferase analysis, miR-22 could significantly suppress the luciferase activity of reporter fused with 3' untranslated region of PTEN mRNA. Furthermore, up-regulation of miR-22 could suppress the protein level of PTEN and reduction of miR-22 level markedly increased the protein level of PTEN in cardiomyocytes by Western blot analysis, suggesting that the contribution of miR-22 to cardiomyocyte hypertrophy may be partially through targeting PTEN. Taken together, miRNAs were dynamically regulated in cardiomyocyte hypertrophy and attenuation of miR-22 in rat cardiomyocytes efficiently protected from hypertrophic effects through derepressing PTEN.

Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy.

MicroRNAs are involved in several aspects of cardiac hypertrophy, including cardiac growth, conduction, and fibrosis. However, their effects on the regulation of the cardiomyocyte cytoskeleton in this pathological process are not known. Here, with microRNA microarray and small RNA library sequencing, we show that microRNA-1 (miR-1) is the most abundant microRNA in the human heart. By applying bioinformatic target prediction, a cytoskeleton regulatory protein twinfilin-1 was identified as a potential target of miR-1. Overexpression of miR-1 not only reduced the luciferase activity of the reporter containing the 3' untranslated region of twinfilin-1 mRNA, but also suppressed the endogenous protein expression of twinfilin-1, indicating that twinfilin-1 is a direct target of miR-1. miR-1 was substantially downregulated in the rat hypertrophic left ventricle and phenylephrine-induced hypertrophic cardiomyocytes, and accordingly, the protein level of twinfilin-1 was increased. Furthermore, overexpression of miR-1 in hypertrophic cardiomyocytes reduced the cell size and attenuated the expression of hypertrophic markers, whereas silencing of miR-1 in cardiomyocytes resulted in the hypertrophic phenotype. In accordance, twinfilin-1 overexpression promoted cardiomyocyte hypertrophy. Taken together, our results demonstrate that the cytoskeleton regulatory protein twinfilin-1 is a novel target of miR-1, and that reduction of miR-1 by hypertrophic stimuli induces the upregulation of twinfilin-1, which in turn evokes hypertrophy through the regulation of cardiac cytoskeleton.

Animal experimental study of the fully biodegradable atrial septal defect (ASD) occluder.

This study was conducted to evaluate the feasibility, safety, biocompatibility, and degradation features of a fully biodegradable occluder for closure of atrial septal defect (ASD) in an acute canine model. The ASD was created in 20 healthy mongrel dogs by the brockenbrough needle, and the fully biodegradable occluders were implanted by self-made delivery system. The success rate and complications were observed. Acute ASD models were successfully created in 18 dogs, and 16 occluders were successfully implanted in the ASD models. Animals were sacrificed at different times after procedure. The cardiac gross anatomy showed that all occluders were stable in the interatrial septum, no vegetation or thrombus formation was observed on the surface of all occluders. They were embedded into endogenous host tissue gradually at 12-week follow-up. Different periods of pathological observations suggested that the occluders degraded gradually over about 24 weeks and essentially became an integral part of the septum. Transcatheter closure of ASD in acute canine model using the fully biodegradable ASD occluder has the potential of a high successful rate of technique, excellent biocompatibility, and fewer complications with adequate, immediate, and short-term results.

Arrhythmias after transcatheter closure of perimembranous ventricular septal defects with a modified double-disk occluder: early and long-term results.

With the development of interventional techniques and devices, transcatheter closure of perimembranous ventricular septal defect has been widely performed. However, there has been a lack of long-term follow-up results about postoperative ECG changes of PmVSD patients. We report our experience of early and late arrhythmias after transcatheter closure of PmVSD with a modified double-disk occluder (MDVO). We performed a retrospective review of 79 patients (47 males, 32 females) between September 2002 and May 2007 who underwent transcatheter closure of perimembranous ventricular septal defect. Symmetric and asymmetric PmVSD occluders were used. The diameter of the evaluated defects ranged from 3 to 12 mm, as measured by TTE and 3 to 15 mm by left ventriculography. Most cases of PmVSD were treated successfully with a single procedure, resulting in a successful closure rate of 97% (77/79 patients). There was no death in any of the patients. After the operation, 79 patients were followed-up for a range of 10-76 months (35.3 ± 17.4 months). In this series, 11 cases of incomplete right bundle branch block and five cases of complete right bundle branch block occurred during the early period after operation. During long-term follow-up, these issues declined in prevalence to five and four cases, respectively. Moreover, reversible third-degree AVB occurred during closure or after the procedure, and two of the three patients with reversible AVB received a temporary heart pacemaker implantation. These patients recovered 1 h, 6 days, and 9 days later, respectively. During 10-76 months of follow-up, no complications occurred in any of the patients, including residual shunt, severe aortic valve, or tricuspid valve regurgitation. Device closure of perimembranous ventricular septal defects with a modified double-disk occluder (MDVO) resulted in excellent closure rates and acceptably low arrhythmia rates.

Intracoronary infusion of bone marrow-derived mononuclear cells contributes to longstanding improvements of left ventricular performance and remodelling after acute myocardial infarction: a meta-analysis.

BACKGROUND: Conflicting results exist now on the sustained effects of intracoronary bone marrow-derived mononuclear cells (BMMNCs) infusion in patients with acute myocardial infarction (AMI). METHODS: Systematical literature search of PubMed, ISI Web of Science, and Cochrane databases was conducted. We included the randomised controlled trials with at least 12-month follow-up data for AMI patients receiving primary percutaneous coronary intervention in addition to intracoronary BMMNCs transfer or not (the control). Summary statistics were calculated using random-effects models. RESULTS: A total of 10 trials with 757 patients were available for analysis. The pooled statistics showed intracoronary administration of BMMNCs significantly improved post-infarction left ventricular ejection fraction (weight mean differences [WMD]=4.04%, 95% confidence intervals [CI], 3.01-5.07%; p<0.01), and attenuated the enlargement of left ventricular end-diastolic volume (WMD=-6.13 ml, 95%CI, -10.56 ml to -1.69 ml; p=0.007) as well as infarct size (WMD=-2.47%, 95%CI, -3.79% to -1.15%; p=0.0002). However, for the major adverse clinical events (MACEs), there appeared to be neutral results (between-group differences of p>0.10). CONCLUSIONS: Intracoronary BMMNCs infusion leads to longstanding and moderate improvements of post-infarction left ventricular performance as well as remodelling. Meanwhile, the procedure did not increase the risk of MACEs.

Potential candidate genes for alveolar hypoxia identified by transcriptome network analysis.

BACKGROUND. Alveolar hypoxia is an important condition related to many disorders such as chronic pulmonary hypertension, pulmonary vasoconstriction, and pulmonary vascular remodeling. The aim of present study was to disclose the biological response and the potential transcriptome networks regulating the hypoxia response in the lungs. MATERIALS AND METHODS. In this study, the microarray dataset GSE11341 was used to construct a regulatory network and identify the potential genes related to alveolar hypoxia. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term enrichment analyses were also performed. RESULTS. Hypoxia inducible factor 1 alpha (HIF-1α), peroxisome proliferator-activated receptor gamma (PPARγ), and nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-кB) were to be the hub nodes in the transcriptome network. HIF-1α may regulate potassium voltage-gated channel, shaker-related subfamily, member (5KCNA5), solute carrier family 2 (facilitated glucose transporter), member (1SLC2A1), and heme oxygenase (decycling) 1 (HMOX1) expression through the regulation of membrane potential, glucose metabolism, and anti-inflammation pathways. HMOX-1 mediates signaling pathways that relate to NF-кB. CCND1 (cyclin D1) expression could be regulated by PPARγ and HIF-1α via the cell cycle pathway. In addition, new transcriptional factors and target genes, such as phosphofructokinase (PFKL, liver), aldolase A (ALDOA, fructose-bisphosphate), and trefoil factor 3 (intestinal) (TFF3), were also identified. CONCLUSIONS. Transcriptome network analysis is a helpful method for the identification of the candidate genes in alveolar hypoxia. The KEGG pathway and GO term analysis are beneficial in the prediction of the underlying molecular mechanism of these identified genes in alveolar hypoxia.

[Safety and efficacy of a domestic made small-waist ventricular septal defect occluder for transcatheter closure of ruptured aneurysm of the sinus of Valsalva].

OBJECTIVE: To evaluate the safety and efficacy of transcatheter closure of ruptured aneurysm of the sinus of Valsalva (RAVS) using a domestic made small-waist ventricular septal defect occluder. METHODS: Between September 2005 and December 2010, transcatheter closure of RAVS was randomly performed in 7 patients of (43.5 ± 13.0) years old using domestic made small-waist ventricular septal defect occluder in our department. RAVS was diagnosed by color Doppler echocardiography. The size of the small-waist double-disk occlude selected was 4 to 6 mm larger than the narrowest diameter of the opening of aneurysm. After establishment of the arteriovenous wire loop, the device was deployed by retrograde venous approach in all patients. All patients were followed up in terms of rhythm change, residual shunt, shape of occlude, and possible valve regurgitation by echocardiography for 6 to 12 months. RESULTS: All RAVS were confirmed by aortography. Aortography showed rupture of right coronary sinus into the right ventricle in 6 patients and non-coronary sinus ruptured into right ventricle in another patient. The estimated size of the defect was 4 to 7 (5.0 ± 1.3) mm by aortogram. Ventricular septal defect was evidenced in 2 patients. All defects were successfully occluded without complication. Two patients with ventricular septal defect received combined percutaneous ventricular septal defect closure. After transcatheter RAVS occlusion, pulmonary artery systolic pressure decreased from (35.6 ± 12.7) mm Hg (1 mm Hg = 0.133 kPa) to (27.4 ± 6.2) mm Hg (P < 0.05), and mean pulmonary artery pressure decreased from (21.9 ± 8.0) mm Hg to (16.1 ± 5.3) mm Hg (P < 0.05). Cardiac murmur disappeared right after successful occlusion. Echocardiography detected a trace of residual shunt in one patient after occlusion which disappeared the next day. There was no aortic regurgitation, hemolysis and arrhythmia during hospitalization. There was no device embolization, infective endocarditis, right heart failure and death during the 6 to 12 months follow-up. CONCLUSION: Transcatheter closure of RAVS with the domestic made small-waist ventricular septal defect occluder is safe and effective.