Functional BMP receptor in endocardial cells is required in atrioventricular cushion mesenchymal cell formation in chick

Transformation of atrioventricular (AV) canal endocardium into invasive mesenchyme correlates spatially and temporally with the expression of bone morphogenetic protein (BMP)-2 in the AV myocardium. We revealed the presence of mRNA of Type I BMP receptors, BMPR-1A (ALK3), BMPR-1B (ALK6) and ALK2 in chick AV endocardium at stage-14(-), the onset of epithelial to mesenchymal transformation (EMT), by RT-PCR and localized BMPR-1B mRNA in the endocardium by in situ hybridization. To circumvent the functional redundancies among the Type I BMP receptors, we applied dominant-negative (dn) BMPR-1B-viruses to chick AV explants and whole-chick embryo cultures to specifically block BMP signaling in AV endocardium during EMT. dnBMPR-1B-virus infection of AV endocardial cells abolished BMP-2-supported AV endocardial EMT. Conversely, caBMPR-1B-virus infection promoted AV endocardial EMT in the absence of AV myocardium. Moreover, dnBMPR-1B-virus treatments significantly reduced myocardially supported EMT in AV endocardial-myocardial co-culture. AV cushion mesenchymal cell markers, alpha-smooth muscle actin (SMA), and TGFbeta3 in the endocardial cells were promoted by caBMPR-1B and reduced by dnBMPR-1B infection. Microinjection of the virus into the cardiac jelly in the AV canal at stage-13 in vivo (ovo) revealed that the dnBMPR-1B-virus-infected cells remained in the endocardial epithelium, whereas caBMPR-1B-infected cells invaded deep into the cushions. These results provide evidence that BMP signaling through the AV endocardium is required for the EMT and the activation of the BMP receptor in the endocardium can promote AV EMT in the chick.     

Percutaneous mitral valve repair using the edge-to-edge technique in a high-risk population

Background. Percutaneous mitral valve (MV) repair using the edge-to-edge clip technique might be an alternative for patients with significant mitral regurgitation (MR) and an unacceptably high risk for operative repair or replacement. We report the short-term safety and efficacy of this new technique in a high-risk population. Methods. All consecutive high-risk patients who underwent percutaneous MV repair with the Mitraclip^® between January and August 2009 were included. All complications related to the procedure were reported. Transthoracic echocardiography for MR grading and right ventricular systolic pressure (RVSP) measurement were performed before, and at three and 30 days after the procedure. Differences in NYHA functional class and quality of life (QoL) index were reported. Results. Nine patients were enrolled (78% male, age 75.9±9.0 years, logistic EuroSCORE 33.8±9.0%). One patient developed inguinal bleeding. In one patient partial clip detachment occurred, a second clip was placed successfully. The MR grade before repair was ≥3 in 100%, one month after repair a reduction in MR grade to ≤2 was present in 78% (p=0.001). RVSP decreased from 43.9±12.1 to 31.6±11.7 mmHg (p=0.009), NYHA functional class improved from median 3 (range 3 to 4) to 2 (range 1 to 4) (p=0.04), and QoL index improved from 62.9±16.3 to 49.9±30.7 (p=0.12). Conclusion. In high-risk patients, transcatheter MV repair seems to be safe and a reduction in MR can be achieved in most patients, resulting in a short-term improvement of functional capacity and QoL. (Neth Heart J 2010;18:437-43.)     

80岁以上老年人冠状动脉旁路移植术合并瓣膜置换手术的临床分析

目的：总结老年患者行冠状动脉旁路移植术（CABG）合并瓣膜置换（VR）手术的特点及经验。方法：上海交通大学附属第一人民医院心血管外科2001年11月至2010年3月对60例年龄大于80的患者施行冠状动脉搭桥＋瓣膜置换手术,男33例,女27例。年龄80-87岁,平均年龄（83.77±2.45）岁。均为冠心病合并瓣膜病变患者。其中36例患者行冠状动脉旁路移植＋二尖瓣置换手术,15例患者行冠状动脉旁路移植＋主动脉瓣置换手术,9例患者行冠状动脉旁路移植＋双瓣置换手术,同时8例患者行三尖瓣成形手术,3例患者行射频消融手术,1例升主动开成形术。置换生物瓣膜者51例,置换机械瓣膜者9例。CABG平均搭桥（2.13±0.75）根,搭桥材料为左乳内动脉与大隐静脉。结果：全组早期死亡9例（15%）,1例死于术后出血,1例死于多器官功能衰竭,7例死于术后心衰。早期生存51例（85%）,出现术后并发症10例,其中2例发生胸腔积液,1例心包填塞,3例肺部感染,1例心房扑动后发生室颤,3例二次开胸止血。给予相应对症治疗后痊愈出院。门诊随访49例,随访时间1～60个月,心功能I级2例、Ⅱ级29例、Ⅲ级18例、Ⅳ级0例（NYHA分级）。结论：对老年患者行冠脉搭桥＋瓣膜置换手术,只要掌握手术适应证,充分作好术前准备、术中及术后处理,手术治疗可以取得良好效果。     

Molecular mechanisms of congenital heart block

Autoantibody-associated congenital heart block (CHB) is a passively acquired autoimmune condition associated with maternal anti-Ro/SSA antibodies and primarily affecting electric signal conduction at the atrioventricular node in the fetal heart. CHB occurs in 1–2% of anti-Ro/SSA antibody-positive pregancies and has a recurrence rate of 12–20% in a subsequent pregnancy. Despite the long-recognized association between maternal anti-Ro/SSA autoantibodies and CHB, the molecular mechanisms underlying CHB pathogenesis are not fully understood, but several targets for the maternal autoantibodies in the fetal heart have been suggested. Recent studies also indicate that fetal susceptibility genes determine whether an autoantibody-exposed fetus will develop CHB or not, and begin to identify such genes. In this article, we review the different lines of investigation undertaken to elucidate the molecular pathways involved in CHB development and reflect on the hypotheses put forward to explain CHB pathogenesis as well as on the questions left unanswered and that should guide future studies.     

一次性可调压限压式灌肠器的实验研究

目的:研究一次性可调压限压式灌肠器的性能。方法:建立模型,测定模拟体内环境下灌肠治疗时肠管各点的压力和灌肠器可调压限压阀开启时的压力是否一致。结果:测定模拟肠管各点压力与灌肠器的可调压限压阀开启时压力一致。结论:一次性可调压限压式灌肠器的性能达到设计要求,操作简便,具有科学性、稳定性、安全性,值得推广。     

Arterio-venöse Kurzschlüsse mit Klappenmechanismen im Bereich der dorsalen Haut der Rattenhinterpfote

Zusammenfassung In der dorsalen Haut der Hinterpfoten von Ratten wurden Klappen am Abgang kleinerer Gefäße von großen Arterien beobachtet. Diese Arterien verlaufen in einer subkutanen, größere Gefäße und Nerven führenden Bindegewebsschichte über den Streckersehnen.Die kleineren Gefäße haben den Wandbau einer Vene und zweigen etwa im rechten Winkel von der Arterie ab. An ihrer Abgangsstelle ist neben den Klappen manchmal ein sphinkterartiger Muskelring ausgebildet.Diese Gefäßabschnitte werden für arterio-venöse Anastomosen gehalten und auf die Bedeutung solcher an dieser Stelle bisher nicht beschriebenen Verschlußeinrichtungen für die Regulation der Kurzschlüsse wird hingewiesen.

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Arteriovenous anastomoses with valve mechanisms in the dorsal skin of the hindpaw of rats

Summary In the dorsal skin of the hindpaws of rats valves were observed at those sites where smaller vessels branched from larger arteries. These arteries run in a subcutaneous layer of connective tissue, which lies above the extensor tendons and in which the larger vessels and nerves are found.These smaller vessels, the walls of which resemble those of veins, were seen branching off at approximate right angles to their artery of origin. Besides the valves a sphincterlike muscle ring was observed in some cases at the point of branching.These vascular segments are held to be arteriovenous anastomoses. Such locking devices at these points have not been described until now and seem to be important in the regulation of arteriovenous shunts.

     

Dynamic changes in endoglin expression in the developing mouse heart

Endoglin (ENG) is essential for cardiovascular development and is expressed in the heart from its earliest developmental stages. ENG expression has been reported in the cardiac crescent, endocardium, valve mesenchyme and coronary vascular endothelial cells. However, its expression in these cell types is non-uniform and the dynamic changes in ENG expression during heart development have not been systematically studied.Using immunofluorescent staining we tracked ENG protein expression in mouse embryonic hearts aged from 11.5 to 17.5 days, and in postnatal and adult hearts. ENG is expressed in the endocardium and in venous endothelial cells throughout these developmental stages. ENG protein is down-regulated by approximately two-fold as a subset of early coronary veins reprogram to form arteries within the developing myocardium from E13.5. This two-fold higher ratio of ENG protein in veins versus arteries is maintained throughout cardiac development and in the adult heart.ENG is also down-regulated two-fold following mesenchymal transition of endocardial cells to form cardiac valve mesenchyme, whilst expression of the pan-endothelial marker CD31 is completely lost. A subset of epicardial cells (which do not express ENG protein) delaminate and undergo a similar mesenchymal transition to form epicardially derived cells (EPDCs). This transient intra-myocardial mesenchymal cell population expresses low levels of ENG protein, similar to valve mesenchyme.In conclusion, ENG shows dynamic changes of expression in vascular endothelial cells, endocardial cells and mesenchymal cells in the developing heart that vary according to cardiovascular cell type.     

Engineering Fibrin-based Tissue Constructs from Myofibroblasts and Application of Constraints and Strain to Induce Cell and Collagen Reorganization

Collagen content and organization in developing collagenous tissues can be influenced by local tissue strains and tissue constraint. Tissue engineers aim to use these principles to create tissues with predefined collagen architectures. A full understanding of the exact underlying processes of collagen remodeling to control the final tissue architecture, however, is lacking. In particular, little is known about the (re)orientation of collagen fibers in response to changes in tissue mechanical loading conditions. We developed an in vitro model system, consisting of biaxially-constrained myofibroblast-seeded fibrin constructs, to further elucidate collagen (re)orientation in response to i) reverting biaxial to uniaxial static loading conditions and ii) cyclic uniaxial loading of the biaxially-constrained constructs before and after a change in loading direction, with use of the Flexcell FX4000T loading device. Time-lapse confocal imaging is used to visualize collagen (re)orientation in a nondestructive manner.Cell and collagen organization in the constructs can be visualized in real-time, and an internal reference system allows us to relocate cells and collagen structures for time-lapse analysis. Various aspects of the model system can be adjusted, like cell source or use of healthy and diseased cells. Additives can be used to further elucidate mechanisms underlying collagen remodeling, by for example adding MMPs or blocking integrins. Shape and size of the construct can be easily adapted to specific needs, resulting in a highly tunable model system to study cell and collagen (re)organization.     

Usefulness Of Ivabradine To Treat "unexpected" Heart Failure Caused By "acute" Right Ventricular Pacing

We present the case of a patient with a heart failure episode induced by acute right ventricular pacing. After reversal of beta-blockers because of chronic obstructive pulmonary disease (COPD) exacerbation, the following sinus tachycardia caused a 2:1 atrioventricular block and consequent continuous right ventricular pacing. He was treated with the selective I(f) inhibitor ivabradine, that reduced both ventricular pacing percentage and heart rate without affecting atrioventricular conduction. Ivabradine may be a valuable option in treatment of patients with atrioventricular conduction disturbances.