Progress of Transmural Healing in Crohn’s Disease

Recently transmural healing (TH) has become a subject of increasing interest as a potential therapeutic purpose for inflammatory bowel disease (IBD). Crohn’s disease (CD) is characterized by chronic inflammation of the gastrointestinal tract, which can involve any part of the digestive tract, and the lesions are usually discontinuous, with progressive and destructive transmural lesions that can lead to irreversible damage such as fibrotic strictures, complications such as fistulas and abscesses. Disease remission remains the primary goal of therapeutic management;however transmural healing is a very promising endpoint for monitoring treatment response. Along with small bowel imaging tests such as computed tomography scans Intestinal imaging (CTE), magnetic resonance intestinal imaging (MRE), intestinal ultrasound (IUS) and other related imaging technologies are popularized in CD diagnosis and treatment benefit. Transmural healing has been initially used in clinical practice and the correlation between its rules and long-term clinical remission has been explored.

Short-and long-term results of endoscopic ultrasoundguided transmural drainage for pancreatic pseudocysts and walled-off necrosis

AIM To evaluate the short-and long-term results of endoscopic ultrasound-guided transmural drainage(EUS-GTD) for pancreatic fluid collection(PFC) and identify the predictive factors of treatment outcome for walled-off necrosis(WON) managed by EUS-GTD alone.METHODS We investigated 103 consecutive patients with PFC who underwent EUS-GTD between September 1999 and August 2015. Patients were divided into four groups as follows: WON(n = 40), pancreatic pseudocyst(PPC; n = 11), chronic pseudocyst(n = 33), and others(n = 19). We evaluated the short-and long-term outcomes of the treatment. In cases of WON, multiple logistic regression analyses were performed to identify the predictor variables associated with the treatment success. In addition, PFC recurrence was examined in patients followed up for more than 6 mo and internal stent removal after successful EUS-GTD was confirmed.RESULTS In this study, the total technical success rate was 96.1%. The treatment success rate of WON, PPC, chronic pseudocyst, and others was 57.5%, 90.9%, 91.0%, and 89.5%, respectively. Contrast-enhanced computed tomography using the multivariate logistic regression analysis revealed that the treatment success rate of WON was significantly lower in patients with more than 50% pancreatic parenchymal necrosis(OR = 17.0; 95%CI: 1.9-150.7; P = 0.011) and in patients with more than 150 mm of PFC(OR = 27.9; 95%CI: 3.4-227.7; P = 0.002).The recurrence of PFC in the long term was 13.3%(median observation time, 38.8 mo). Mean amylase level in the cavity was significantly higher in the recurrence group than in the no recurrence group(P = 0.02).CONCLUSION The reduction of WON by EUS-GTD alone was associated with the proportion of necrotic tissue and extent of the cavity. The amylase level in the cavity may be a predictive factor for recurrence of PFC.

Nomogram for predicting transmural bowel infarction in patients with acute superior mesenteric venous thrombosis

BACKGROUND The prognosis of acute mesenteric ischemia(AMI)caused by superior mesenteric venous thrombosis(SMVT)remains undetermined and early detection of transmural bowel infarction(TBI)is crucial.The predisposition to develop TBI is of clinical concern,which can lead to fatal sepsis with hemodynamic instability and multi-organ failure.Early resection of necrotic bowel could improve the prognosis of AMI,however,accurate prediction of TBI remains a challenge for clinicians.When determining the eligibility for explorative laparotomy,the underlying risk factors for bowel infarction should be fully evaluated.AIM To develop and externally validate a nomogram for prediction of TBI in patients with acute SMVT.METHODS Consecutive data from 207 acute SMVT patients at the Wuhan Tongji Hospital and 89 patients at the Guangzhou Nanfang Hospital between July 2005 and December 2018 were included in this study.They were grouped as training and external validation cohort.The 207 cases(training cohort)from Tongji Hospital were divided into TBI and reversible intestinal ischemia groups based on the final therapeutic outcomes.Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for TBI using the training data,and a nomogram was subsequently developed.The performance of the nomogram was evaluated with respect to discrimination,calibration,and clinical usefulness in the training and external validation cohort.RESULTS Univariate and multivariate logistic regression analyses identified the following independent prognostic factors associated with TBI in the training cohort:The decreased bowel wall enhancement(OR=6.37,P<0.001),rebound tenderness(OR=7.14,P<0.001),serum lactate levels>2 mmol/L(OR=3.14,P=0.009)and previous history of deep venous thrombosis(OR=6.37,P<0.001).Incorporating these four factors,the nomogram achieved good calibration in the training set[area under the receiver operator characteristic curve(AUC)0.860;95%CI:0.771-0.925]and the external validation set(AUC 0.851;95%CI:0.796-0.897).The positive and negative predictive values(95%CIs)of the nomogram were calculated,resulting in positive predictive values of 54.55%(40.07%-68.29%)and 53.85%(43.66%-63.72%)and negative predictive values of 93.33%(82.14%-97.71%)and 92.24%(85.91%-95.86%)for the training and validation cohorts,respectively.Based on the nomogram,patients who had a Nomo-score of more than 90 were considered to have high risk for TBI.Decision curve analysis indicated that the nomogram was clinically useful.CONCLUSION The nomogram achieved an optimal prediction of TBI in patients with AMI.Using the model,the risk for an individual patient inclined to TBI can be assessed,thus providing a rational therapeutic choice.

Experimental Study of the Effect of Autonomic Nervous System on the Transmural Dispersion of Ventricular Repolarization under Acute Myocardial Ischemia in Vivo

Summary: The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization (TDR) under acute myocardial ischemia in intact canine was investigated. Using the monophasic action potential (MAP) recording technique, MAPs of the epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs. MAPD 90 and TDR among three myocardial layers as well as the incidence of the early afterdepolarization (EAD) before autonomic nervous stimulation and during autonomic nervous stimulation were compared. It was found that 10 min after acute myocardial ischemia, TDR was increased from 55±8 ms to 86±15 ms during sympathetic stimulation (P<0.01). The TDR (53±9 ms) during parasympathetic stimulation was not significantly different from that of the control (55±8 ms) (P>0.05). The EAD was elicited in the Mid of 2 dogs (16 %) 10 min after acute myocardial ischemia, but the EAD were elicited in the Mid of 7 dogs (58 %) during sympathetic stimulation (P<0.01). It was concluded that: (1) Sympathetic stimulation can increase the transmural dispersion of repolari-zation and induce early afterdepolarizations in the Mid under acute myocardial ischemia, which provide the opportunity for the ventricular arrhythmia developing; (2) Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia.

Effect of Autonomic Nervous System on the Transmural Dispersion of Ventricular Repolarization in Intact Canine

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization in intact canine was investigated. By using the monophasic action potential (MAP) recording technique, monophasic action potentials (MAPs) of the epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge needle electrodes at the left ventricular free wall in 12 open chest dogs. MAPD 90 and transmural dispersion of repolarization among three myocardial layers as well as the incidence of the EAD before autonomic nervous stimulation and during autonomic nervous stimulation were compared. The results showed that the MAPD 90 of Epi, Mid and Endo before autonomic nervous stimulation were 278±11 ms, 316±16 ms and 270±12 ms respectively, the MAPD 90 of Mid was significantly longer than that of Epi or Endo ( P <0.01). MAPD 90 of Epi, Mid and Endo were shortened by 19±4 ms, 45±6 ms, 18±3 ms respectively during sympathetic stimulation. Compared with that of the control, the transmural dispersion of repolarization during sympathetic stimulation was shortened from 44±4 ms to 15±3 ms ( P <0.01), but early afterdepolarizations were elicited in the Mid of 5 dogs (41 %) during sympathetic stimulation. Parasympathetic stimulation did not significantly affect the MAPD 90 in the three layers. It is concluded that there is the transmural dispersion of ventricular repolarization in intact canine. Sympathetic stimulation can reduce transmural dispersion of repolarization, but it can produce early afterdepolarizations in the Mid. Parasympathetic stimulation does not significantly affect the transmural dispersion of ventricular repolarization.

Treat-to-target in Crohn's disease:Will transmural healing become a therapeutic endpoint?

Crohn's disease(CD) represents a chronic transmural inflammatory condition of the gastrointestinal tract, which usually leads to structural damage and signific-ant disability. Deep remission--defined by both clinical and endoscopic remission, signifying mucosal healing-represents the current endpoint in the treat--to--target strategy, significantly improving patients' long--term outcomes. Transmural healing(TH) could be a more effe-ctive target, but this possibility remains unclear. This narrative review aims to critically review and summarize the available literature relating TH to long--term outcomes, being the first of its kind and to the best of the author's knowledge. A systematic literature search(from incep-tion to March 31 2018) was performed, using multiple databases, and identifying seven full--text manuscripts. In those studies, long--term favorable outcomes(≥ 52 wk) included sustained clinical remission, as well as fewer therapeutic changes, CD--related hospitalizations, and surgeries. Despite heterogeneous design and me-thodological limitations, six of the studies demonstrated that TH or intestinal healing(TH plus mucosal healing) were predictive for the aforementioned favorable out-comes. Therefore, TH may become a reasonable the-rapeutic target and be included in the concept of deep remission. Further prospective, well-designed, multicenter trials aiming to better define the role of TH in personalized therapy for CD and to determine the long-term influence of TH on bowel damage and disability are warranted.

Transmural myocardial ischemia due to slow coronary flow

Slow coronary flow phenomenon(SCFP) is an angiographic observation characterized by delayed distal vessel opacifi-cation in the absence of significant epicardial coronary disease. Only limited studies have been focused on the etiologies,clinical manifestations and treatment of this unique angiographic phenomenon. In our case report,we described an 85-year-old man who came with significant ST segment elevation in leads V1-V4 and V3R-V5R without increase in myocardial enzyme. The patient also developed respiratory failure requiring intubation and mechanical ventilation. Coronary angiography revealed only mild atherosclerosis without spasm or thromboembolic occlusion. Slow flow was seen in all coronary arteries,especially in the left anterior descending and right coronary arteries. This case speculated that transmural myocardial ischemia with ST segment elevation might be resulted from slow coronary flow. Transmural myocardial ischemia can occur owing to abnormalities of the coronary microcirculation.

Colonic perforation by a transmural and transvalvular migrated retained sponge:Multi-detector computed tomography findings

Transmural migrated retained sponges usually impact at the level of the ileo-cecal valve leading to a small bowel obstruction.Once passed through the ileo-cecal valve,a retained sponge can be propelled forward by peristaltic activity and eliminated with feces.We report the case of a 52-year-old female with a past surgical history and recurrent episodes of abdominal pain and constipation.On physical examination,a generalized resistance was observed with tenderness in the right flank.Contrast-enhanced multi-detector computed tomography findings were consistent with a perforated right colonic diverticulitis with several out-pouchings at the level of the ascending colon and evidence of free air in the right parieto-colic gutter along with an air-fluid collection within the mesentery.In addition,a ring-shaped hyperdense intraluminal material was also noted.At surgery,the ascending colon appeared irregularly thickened and folded with a focal wall interruption and a peri-visceral abscess at the level of the hepatic flexure,but no diverticula were found.A right hemi-colectomy was performed and on dissection of the surgical specimen a retained laparotomy sponge was found in the bowel lumen.

Die Transmurale ERP-Dispersion von Epi-,Mid-und Endomyokard im gesunden und hypertrophierten Hundemyokard

Viele Studien haben das Vorliegen von M Zellen im Midmyokard des Hundes in vitro beobachtet und weiterhin gefunden, da das Vorliegen von M Zellen zur Differenz der Repolarisation und zur Dispersion der Refraktarzeit zwischen Midmyokard und Epi und Endomyokard fuhren kann.Diese Dispersion hat enge Beziehungen mit der Entstehung der Arrhythmie. Aber die Beobachtungen in vitro waren nicht konkordant mit den Ergebnissen in vivo. Mittels direkten Messungen der ERP in drei Myokardschichten wurde erstmals im gesunden Hundemyokard und im hypertrophierten Hundemyokard in vivo untersucht. Die Untersuchung hat gezeigt, da die ERP von Endomyokard, Epimyokard und Midmyokard im gesunden Hundeherzen homogen sind. Die relevante transmurale Refraktargradient, die die Induktion einer kreisenden Erregung begunstigt, besteht unter physiologischen Bedingungen nicht. Im Gegensatz dazu konnte eine deutliche Verlangerung der ERP in allen Myokardschichten von hypertrophierten Hundeherzen nachgewiesen werden.. Weiterhin wurde gezeigt, da eine transmurale ERP Dispersion zwischen verschiedenen Myokardschichten im hypertrophierten Hundemyokard besteht. Es ist zu postulieren, da diese transmurale ERP Dispersion als Substrat fur die Arrhythmie angesehen werden kann,weil diese Dispersion die lokalen kreisende Erregung zwischen Epikard und Midkard, oder zwischen Midkard und Endokard begunstigen kann. Nach den Ergebnissen lat sich postulieren, da eine transmurale ERP Dispersion durch eine plotzliche Zykluslangeveranderung, namlich durch eine Kurz Lang und eine Lang Kurz Sequenz verstarkt werden kann.

Effects of Amiodarone on Transmural Dispersion of Ventricular Effective Refractory Periods across Myocardial Layers in the Normal and Hypertrophic Canine Heart

The effects of amiodarone on transmural dispersion of ventricular effective refractory periods （ERPs） in the normal and hypertrophic canine heart were investigated in vivo. By using the programmed stimulation protocol, the ERPs of epicardium （Epi）, midmyocardium （Mid） and endocardium （Endo） were measured by inserting specially-designed electrodes into the three myocardial layers before and after mainlining of amiodarone. No significant ERPs-dispersion was observed in the three layers before and after mainlining of amiodarone in the normal group. In contrast, ERPs of all the three layers were prolonged in the hypertrophic heart, while the ERPs-dispersion was reduced significantly after mainlining of amiodarone. The ERPs-dispersion was significantly increased in the hypertrophic heart but not in the normal heart using ＂long-short＂ and ＂short-long＂ interval stimulation technique. It was concluded that （1） the differences in ERPs-dispersion among the three layers were significant in hypertrophic heart, and differences were not significant in normal canine heart; （2） ERPs of each three-myocardial layers were significantly prolonged after using amioda- rone, but the ERPs-dispersion decreased in hypertrophic heart and （3） the programmed extrastimulus technique of ＂long-short＂ and ＂short-long＂ intervals increased the transmural ERPs-dispersion in the hypertrophic heart.

Treat to target in Crohn’s disease:A practical guide for clinicians

A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.

Changes of Monophasic Action Potential Duration and Effective Refractory Period of Three Layers Myocardium of Canine during Acute

Summary： The effect of acute ischemia on the electrophysiological characteristics of the three layers myocardium of canine in vivo was investigated. Twelve canines were divided into two groups randomly： acute ischemia （AI） group and sham operation （SO） group. By using the monophasic action potential （MAP） technique, MAP and effective refractory period （ERP） of the three layers myocardium were measured by specially designed plunge needle electrodes and the transmural dispersion of repolarization （TDR） and transmural dispersion of ERP （TDE） were analyzed. The results showed that in the AI group, MAP duration （MAPD） was shortened from 201.67±21.42 ms to 169.50±13.81 ms （P〈0.05）, but ERP prolonged to varying degrees and TDE increased during ischemia. In the SO group, MAPD and ERP did not change almost. Among of the three layers myocardium of canine, MAPD was coincident in two groups. It was concluded that during acute ischemia, MAPD was shortened sharply, but there was no significant difference among of the three layers myocardium. The prolonged ERP was concomitant with increased TDE during acute ischemia, which may play an important role in the occurrence of arrhythmias induced by acute ischemia. These findings may have important implications in arrhythmogenesis.

Effects of ramipril on ventricular arrhythmia after myocardial infarction in rabbits

BACKGROUND: V entricular arrhythmia(VA) is one of the most common complications of myocardial infarction(MI), and ventricular tachycardia and fi brillation are the main causes for sudden cardiac death. This study aimed to explore the effect of ramipril on the occurrence of VA and its mechanism after MI in rabbits.METHODS: Twenty-four New Zealand rabbits purchased from the Wuhan Laboratory Animal Research Center were divided into three groups: sham-operated(SHAM) group(n=8), MI group(n=8) and MI with ramipril(RAM) group(n=8). Rabbits in the SHAM group received a median sternotomy without ligation of the left ventricular coronary artery. Rabbits in the MI and RAM groups received a median sternotomy followed by ligation of the left coronary artery. The successful anterior MI was confi rmed by elevation of the ST segment with more than 0.2 mV in lead II and III. After MI, rabbits in the RAM group were fed with intragastric ramipril(1 mg/kg per day) for 12 weeks. Before and 12 weeks after MI in the three groups, ventricular tachycardia or fi brillation(VT/VF) episodes and MAP in cadiocytes of the epicardium, mid-myocardium and endocardium were recorded by a multichannel physiograph. Student's t test and ANOVA were used for statistical analysis.RESULTS: VT/VF episodes were decreased more markedly in the RAM group than in the MI group after 12 weeks(2.6±0.8 vs. 12.4±2.9, P<0.05). Twelve weeks after MI, the duration of repolarization for 90%(APD90) of three-tier ventricular myocytes in the MI group was longer than that before MI(258.2±21.1 vs. 230.1±23.2, 278.0±23.8 vs. 245.8±25.4, 242.6±22.7 vs. 227.0±21.7, P<0.05). However, the APD90 was not signif icantly different at 12 weeks before and after MI in the RAM group(P>0.05). Moreover, the transmural dispersion of repolarization(TDR) was increased more markedly 12 weeks after MI in the MI group than in the SHAM and RAM groups(36.2±10.2 vs. 18.7±6.2, 24.9±8.7, P<0.05). But the TDR was not signifi cantly different between the RAM and SHAM groups(18.7±6.2 vs. 24.9±8.7, P>0.05).CONCLUSION: Ramipril may reduce the incidence of malignant ventricular arrhythmia via improvement of transmembrance repolarization heterogeneity after MI.

A biomimetic basementmembrane consisted of hybrid aligned nanofibers andmicrofibers with immobilized collagen IV and laminin for rapid endothelialization

Rapid formation of a continuous endothelial cell(EC)monolayer with healthy endothelium function on the luminal surface of vascular implants is imperative to improve the longtime patency of small-diameter vascular implants.In the present study,we combined the contact guidance effects of aligned nanofibers,which enhance EC adhesion and proliferation because of its similar fiber scale with native vascular basement membranes,and aligned microfibers,which could induce EC elongation effectively and allow ECs infiltration.It was followed by successive immobilization of collagen IV and laminin to fabricate a biomimetic basement membrane(BBM)with structural and compositional biomimicry.The hemolysis assay and platelet adhesion results showed that the BBM exhibited excellent hemocompatibility.Meanwhile,the adhered human umbilical vein endothelial cells(HUVECs)onto theBBMaligned along the orientation of the microfibers with an elongated morphology,and the data demonstrated that the BBM showed favorable effects on EC attachment,proliferation,and viability.The oriented EC monolayer formed on the BBM exhibited improved antithrombotic capability as indicated by higher production of nitric oxide and prostacyclin(PGI2).Furthermore,fluorescence images indicated that HUVECs could infiltrate into the BBM,implying theBBM’s ability to enhance transmural endothelialization.Hence,theBBMpossessed the properties to regulate ECbehaviors and allow transmural ingrowth,demonstrating the potential to be applied as the luminal surface of small-diameter vascular implants for rapid endothelialization.

Electrocautery vs non-electrocautery dilation catheters in endoscopic ultrasonography-guided pancreatic fluid collection drainage

AIM: To investigate the safety and utility of an electrocautery dilation catheter for endoscopic ultrasonography(EUS)-guided pancreatic fluid collection drainage.METHODS: A single-center, exploratory, retrospective study was conducted between August 2010 and August 2014. This study was approved by the Medical Ethics Committee of our institution. Informed, written consent was obtained from each patient prior to the procedure. The subjects included 28 consecutive patients who underwent EUS-guided transmural drainage(EUS-TD) for symptomatic pancreatic and peripancreatic fluid collections(PFCs) by fine needle aspiration using a 19-gauge needle. These patients were retrospectively divided into two groups based on the use of an electrocautery dilation catheter as a fistula dilation device; 15 patients were treated with an electrocautery dilation catheter(electrocautery group), and 13 patients were treated with a non-electrocautery dilation catheter(non-electrocautery group). We evaluated the technical and clinical successes and the adverse events associated with EUS-TD for the treatment of PFCs between the two groups.RESULTS: There were no significant differences in age, sex, type, location and diameter of PFCs between the groups. Thirteen patients(87%) in the electrocauterygroup and 10 patients(77%) in the non-electrocautery group presented with infected PFCs. The technical success rates of EUS-TD for the treatment of PFCs were 100%(15/15) and 100%(13/13) for the electrocautery and the non-electrocautery groups, respectively. The clinical success rates of EUS-TD for the treatment of PFCs were 67%(10/15) and 69%(9/13) for the electrocautery and the non-electrocautery groups, respectively(P = 0.794). The procedure time of EUS-TD for the treatment of PFCs in the electrocautery group was significantly shorter than that of the non-electrocautery group(mean ± SD: 30 ± 12 min vs 52 ± 20 min, P < 0.001). Adverse events associated with EUS-TD for the treatment of PFCs occurred in 0 patients and 1 patient for the electrocautery and the non-electrocautery groups, respectively(P = 0.942).CONCLUSION: EUS-TD using an electrocautery dilation catheter as a fistula dilation device for the treatment of symptomatic PFCs appears safe and contributes to a shorter procedure time.

Antiarrhythmic peptide AAP10 prevents ventricular arrhythmia in rabbit LQT2 model

Background and Objective Increased transmural dispersion ofrepolarization (TDR) has been shown to contribute to initiation and maintenance of ventricular arrhythmia in long QT syndromes (LQTS).Intercellular uncoupling through gap junctions is an important mechanism for maintaining TDR in both intact and diseased heart.The present study was to test the hypothesis that improving gap junction communication reduces TDR and prevents ventricular arrhythmia in rabbit LQT2 model.Methods An arterially perfused rabbit left ventricular preparation and E4031 (0.5μmol/L) were used to establish a model of LQT2.Preparations were randomly assigned to control (n=10),AAP-100nmol/L(n=10),AAP-500nM(n=10) groups.Transmural ECG as well as action potentials from both endocardium and epicardium was simultaneously recorded.Results In LQT2 model,presence of 500nmol/L AAP 10 reduced endocardial action potential and TDR and prevented ventricular arrhythmia comparing with the control and AAP 100nmol/ L groups (P【0.05).Conclusions The presence of 500 nmol/L AAP10 reduces TDR and prevents ventricular arrhythmia in rabbit ventricular model of LQT2.This study suggests a possible role of GJs in TDR in rabbit LQT2 model and indicates a new clinical approach to the management of LQTS.

Effect of Calcium-Channel Antagonist on Repolarization Heterogeneity of Ventricular Myocardium in an in Vitro Rabbit Model of Long QT Syndrome

Intracellular Ca2＋ and Ca2＋-dependent signaling molecule play an essential role in the genesis of long-QT （LQT） syndrome-related ventricular arrhythmias. The effect of calcium-channel antagonist verapamil on repolarization heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model of LQT syndrome. By using the monophasic action potential （MAP） recording technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously recorded by specially designed plunge-needle electrodes across the left ventricular free wall in rabbit hearts purfused by Langendorff method with standard Tyrode＇s solution. Bradycardia was induced by com- plete ablation of atrioventricular node. A catheter was introduced into the right ventricle to pace at the cycle lengths （CLs） of 1500, 1000, and 500 ms, successively. Quinidine （2 μmol/L） prolonged QT interval and ventricular MAP duration （MAPD）, and increased transmural dispersion of repolarization （TDR） in a reverse rate-dependent fashion in isolated rabbit heart. No polymorphic ventricular tachycardias were induced under this condition. The effective free therapeutic plasma concentrations of verapamil （0.01--0.05μmol/L） used in this experiment had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This study demonstrated that, in this model of LQT syndrome, blockade of calcium-channel with verapmil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.

Endoscopic ultrasound-guided drainage of pancreatic walled-off necrosis using self-expanding metal stents without fluoroscopy

AIM To investigate whether endoscopic ultrasound(EUS)-guided insertion of fully covered self-expandable metal stents in walled-off pancreatic necrosis(WOPN) is feasible without fluoroscopy.METHODS Patients with symptomatic pancreatic WOPN undergoing EUS-guided transmural drainage using self-expandable and fully covered self expanding metal stents(FCSEMS) were included. The EUS visibility of each step involved in the transmural stent insertion was assessed by theoperators as "visible" or "not visible":(1) Access to the cyst by needle or cystotome;(2) insertion of a guide wire;(3) introducing of the diathermy and delivery system;(4) opening of the distal flange; and(5) slow withdrawal of the delivery system until contact of distal flange to cavity wall. Technical success was defined as correct positioning of the FCSEMS without the need of fluoroscopy.RESULTS In total, 27 consecutive patients with symptomatic WOPN referred for EUS-guided drainage were included. In 2 patients large traversing arteries within the cavity were detected by color Doppler, therefore the insertion of FCSEMS was not attempted. In all other patients(92.6%) EUS-guided transgastric stent insertion was technically successful without fluoroscopy. All steps of the procedure could be clearly visualized by EUS. Nine patients required endoscopic necrosectomy through the FCSEMS. Adverse events were two readmissions with fever and one self-limiting bleeding; there was no procedure-related mortality. CONCLUSION The good endosonographic visibility of the FCSEMS delivery system throughout the procedure allows safe EUS-guided insertion without fluoroscopy making it available as bedside intervention for critically ill patients.