Xinmiao Huang

Plasma ghrelin and obestatin levels are increased in spontaneously hypertensive rats.

Obestatin, encoded by the same gene as ghrelin, was first described as a physiological opponent of ghrelin. We investigated fasting plasma ghrelin and obestatin levels in spontaneously hypertensive rats and Wistar-Kyoto rats. We found that ghrelin levels, obestatin levels and the ratio of ghrelin to obestatin were significantly higher in spontaneously hypertensive rats than Wistar-Kyoto rats. Systolic blood pressure and diastolic blood pressure were positively correlated; however, heart period and baroreflex sensitivity were negatively correlated with ghrelin levels. Systolic blood pressure was positively correlated, whereas baroreflex sensitivity was negatively correlated with obestatin levels. In addition, systolic blood pressure was a significantly independent variable of ghrelin levels, obestatin levels, and the ghrelin to obestatin ratio in a multiple regression analysis. Our data suggests that there is a disturbance of ghrelin and obestatin in the circulation of spontaneously hypertensive rats and the ghrelin/obestatin system might play a role in blood pressure regulation.

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.

Endothelial enriched microRNAs regulate angiotensin II-induced endothelial inflammation and migration

The initial stage of atherosclerosis is characterised by recruitment of leukocytes to activate endothelial cells (ECs). MicroRNAs (miRNAs) are a class of 19 to 25 nucleotides, non-protein-coding RNAs that repress target gene expression by translational inhibition or mRNA degradation. The link between miRNA and endothelial functions is largely unknown. Northern blot showed that miR-155 and miR-221 were highly expressed in human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs). Bioinformatics analysis proposed Ets-1, a key endothelial transcription factor for inflammation and tube formation, as a candidate target for miR-155 and miR-221/222 cluster. The effect was demonstrated by luciferase reporter assay and Western blot. By using Western blot, we also confirmed that angiotensin II type 1 receptor (AT1R) is a target of miR-155 in HUVECs. Quantitative PCR showed that Ets-1 and its downstream genes, including VCAM1, MCP1 and FLT1, were up-regulated in angiotensin II-stimulated HUVECs, and this effect was partially reversed by over-expression of miR-155 and miR-221/222. In addition, cell adhesion assay revealed over-expression of miR-155 and miR-221/222 effectively decreased the adhesion of Jurkat T cells to Ang II-stimulated HUVECs. Besides, by targeting AT1R, miR-155 can also decrease the HUVECs migration in response to Ang II. In summary, HUVECs highly expressed miR-155 may co-target AT1R and Ets-1 while miR-221/222 targets Ets-1, which indirectly regulate the expression of several inflammatory molecules of ECs, and therefore attenuate the adhesion of Jurkat T cells to activated HUVECs and reduce HUVECs migration. These findings present possible therapeutic targets in atherosclerosis.

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

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.

Reversal of the Activation Sequence along the Coronary Sinus during RF Application with a Single Left Lateral Pathway

A 16-year-old girl with a 4-year history of recurrent supraventricular tachycardia was referred for catheter ablation. A standard 12-lead electrocardiogram (ECG) during sinus rhythm revealed no abnormalities. Invasive electrophysiologic study was performed. Two quadripolar catheters were inserted via femoral venous access and placed in the high right atrium and right ventricle. A decapolar catheter was inserted via the right internal jugular vein into the coronary sinus with the proximal bipole at the os. Programmed atrial stimulation revealed a continuous atrioventricular (AV) node function curve. Right ventricular pacing at different cycle lengths (CLs) showed nondecremental ventriculoatrial (VA) conduction and the earliest atrial activation at the distal coronary sinus (CS). Rapid ventricular stimulation easily and repeatedly induced a regular narrow QRS complex tachycardia with a CL of 300 ms. The activation sequence on the CS leads during tachycardia is distal to proximal (Fig. 1). A diagnosis of orthodromic AV reentrant tachycardia (AVRT) using a left-sided free-wall accessory pathway (AP) was made. The retrograde transaortal approach was used. Due to difficulty in reaching a left anterolateral position beneath the mitral valve, the ablation catheter was positioned supra the mitral valve in a left anterolateral location. Radiofrequency (RF) energy was delivered to the earliest atrial activation site 4 mm above the distal CS catheter electrode at the mitral annulus. After 3 times RF energy application (10 second × 3) during sinus rhythm, another type of tachycardia was induced (Fig. 2). The catheter in CS were placed 1.5-cm distal to the original site. During tachycardia, CS3–4 electrodes showed double atrial potentials with an interval of 40 ms (Fig. 3). What has happened in Figures 2

Successful catheter ablation of idiopathic premature ventricular contractions originating from the "right" ventricular outflow tract in a patient with dextrocardia and situs inversus viscerum.

Article history: Received 17 June 2015 Accepted 26 June 2015 Available online 2 July 2015 radiofrequency ablation with rare complications. However, after a review of the medical literature, and to our knowledge, there has been only one case report of catheter ablation of PVC in patients with dextrocardia and situs inversus published. Whats more, this is the first case of successful idiopathic “R”VOT-PVC ablation using a three-dimensional mapping system in an adult with dextrocardia and situs inversus viscerum. While the initial case of “R”VOT-PVC ablation in dextrocardia was reported by Bonnemeier et al. last A 65-year-old man was referred for catheter ablation of idiopathic premature ventricular contractions (PVC) because of severe palpitations for more than one year. No abnormality except for right-sided heart sounds was found in the physical examination and laboratory tests, which indicated likely dextrocardia. The chest radiogram and CT further confirmed it and abdominal ultrasound found situs inversus viscerum as well. Electrocardiogram indicated right axis deviation with an inversion of the electrical waves in I, aVR and aVL, as well as sustained ventricular bigeminy. The monomorphic PVC had left bundle branch block (LBBB) with inferior axis after V1–V6 inversed and positioned over the right chest (Fig. 1A). Transthoracic echocardiography revealed a normal “left” ventricular ejection fraction (LVEF 60%) without structural abnormality. The St. Jude Ensite 3000 mapping system was used to make a detailed electroanatomic map of his “right” ventricle. Activation mapping revealed the earliest site of ventricular activation 40 msec earlier than the QRS complex on surface electrocardiogram, which existed in the posterior septum of the “right” ventricular outflow tract (RVOT) (Fig. 2A). Pace mapping at this site showed a 12-lead match between paced beats and arrhythmia complexes. Radiofrequency ablation at this site resulted in PVC termination successfully (Fig. 2B–C) and no PVC could be induced by ventricular stimulation during the subsequent 30 min after the procedure, as well as for the rest of the hospital stay. There was no recurrence of PVC in subsequent 3 month follow-up according to the results of a 24 h-Holter.

Long noncoding RNA MALAT1 mediates cardiac fibrosis in experimental postinfarct myocardium mice model: HUANG et al.

Cardiac fibrosis is a pathological remodeling response to myocardial infarction (MI) and impairs cardiac contractility. Long noncoding RNA (lncRNA) metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is increased in patients with MI. However, the functions of MALAT1 in cardiac fibrosis have not been elucidated. This study elucidates the roles of MALAT1 in MI and the underlying mechanisms. The MI model was established by artificial coronary artery occlusion in mice. Western blot analysis and quantitative reverse transcription‐polymerase chain reaction were performed to analyze protein expression and RNA expression, respectively. Cardiac function was measured by echocardiography. Masson’s trichrome staining was used to exhibit the fibrotic area in MI hearts. Cardiac fibroblasts were isolated from newborn pups, and cell proliferation was determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Upregulation of MALAT1 and downregulation of microRNA‐145 (miR‐145) were induced in MI heart and angiotensin II (AngII)‐treated cardiac fibroblasts, and the inhibition of miR‐145 expression was reversed by MALAT1 depletion. Knockdown MALAT1 ameliorated MI‐impaired cardiac function and prevented AngII‐induced fibroblast proliferation, collagen production, and α‐SMA expression in cardiac fibroblasts. MALAT1 stability and transforming growth factor‐β1 (TGF‐β1) activity were regulated by miR‐145. AngII‐induced TGF‐β1 activity in cardiac fibroblasts was blocked by MALAT1 knockdown. Based on these results, we concluded that lncRNA MALAT1 promotes cardiac fibrosis and deteriorates cardiac function post‐MI by regulating TGF‐β1 activity via miR‐145.

Transthoracic left atrial appendage reverse occlusion:instrument development and in vitro animal experiment

Objective To design and prepare a glass-shaped transthoracic left atrial appendage(LAA)reverse occluder and delivery system,and to evaluate the feasibility of transthoracic left atrial appendage reverse occlusion by in vitro reverse occlusion experiment.Methods We used fresh canine heart specimens and measured the anatomical parameters,including the long diameter,short diameter and perimeter of atrial appendage opening,the thickness of upper 1/3left atrial appendage,the shortest distances from the edge of the opening of the atrial appendage to the left superior pulmonary vein,the left inferior pulmonary vein,and the mitral valve.A new glass-shaped left atrial appendage occluder was designed using nitinol wire,and the appendage occluder opening disk diameter and waist height were designed according to the average diameter of the opening of the atrial appendage and the thickness of upper 1/3left atrial appendage.The delivery system comprised 9Fdelivery sheath,expansion sheath,preload sheath and a pushing cable.Delivery sheath was scaled which can be used to control the depth into the left atrial appendage,and expansion sheath head end had smooth transition shape which exposed only about 0.8cm when inserted into the delivery sheath to prevent damage internal of tissue of heart.Ten isolated dog hearts were punctured at the center of the upper 1/3axis of left atrial appendage outside under direct vision,and 9Fsheath with scale was used to complete in vitro experiment of occlusion.The location and effect of the occluder were observed.Results Nine of the 10 heart specimens successfully underwent the occluding tests in vitro.It was showed that the occluder was well located,with the disc of the opening of left atrial appendage porting into the opening a little and the opening in an overdistraction state,and there was no influence on blood flow of pulmonary vein or function of the mitral valve.The ideal point of puncture was at the upper 1/3long axis of left atrial appendage outside,and the purse-string suture should focus on this point.The puncture points located at the center of the left atrial appendage opening after removing the occluder postoperatively.Only 1case failed because of low puncture point and unsuitable location of the occluder.Conclusion The glass-shaped transthoracic reverse occluder is welldesigned and matched the anatomy of left the atrial appendage in experimental canine.The occluding effects are exact and meet the requirements of animal experiments in vivo.

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.

A new coated nitinol occluder for transcatheter closure of ventricular septal defects in a canine model.

Aims. This study evaluated feasibility and safety of implanting the polyester-coated nitinol ventricular septal defect occluder (pcVSDO) in the canine model. Methods and Results. VSD models were successfully established by transseptal ventricular septal puncture via the right jugular vein in 15 out of 18 canines. Two types of VSDOs were implanted, either with pcVSDOs (n = 8) as the new type occluder group or with the commercial ventricular septal defect occluders (VSDOs, n = 7, Shanghai Sharp Memory Alloy Co. Ltd.) as the control group. Sheath size was 10 French (10 Fr) in two groups. Then the general state of the canines was observed after implantation. ECG and TTE were performed, respectively, at 7, 30, 90 days of follow-up. The canines were sacrificed at these time points for pathological and scanning electron microscopy examination. The devices were successfully implanted in all 15 canines and were retrievable and repositionable. There was no thrombus formation on the device or occurrence of complete heart block. The pcVSDO surface implanted at day 7 was already covered with neotissue by gross examination, and it completed endothelialization at day 30, while the commercial VSDO was covered with the neotissue in 30th day and the complete endothelialization in 90th day. Conclusion. The study shows that pcVSDO is feasible and safe to close canine VSD model and has good biocompatibility and shorter time of endothelialization.