首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 78 毫秒
1.

Background

Pulmonary vein (PV) reconduction after PV isolation (PVI) unmasked by adenosine is associated with a higher risk for paroxysmal atrial fibrillation (PAF) recurrence. It is unknown if the reconnected PVs after adenosine testing and immediate re-ablation can predict reconnection and reconnection patterns of PVs at repeat procedures. We assessed reconnection of PVs with and without dormant-conduction (DC) during the first and the repeat procedure.

Methods

We included 67 patients undergoing PVI for PAF and a second procedure for PAF recurrence. DC during adenosine administration at first procedure was seen in 31 patients (46%). 264 PVs were tested with adenosine; DC was found in 48?PVs (18%) and re-ablated during first procedure. During the second procedure, all PVs where checked for reconnection.

Results

Fifty-eight patients (87%) showed PV reconnection during the second procedure. Reconnection was found in 152/264?PVs (58%). Of 216?PVs without reconnection during adenosine testing at the first ablation, 116?PVs (53.7%) showed reconnection at the repeat procedure. Overall, 14.9% of patients showed the same PV reconnection pattern in the first and second procedure, expected statistical probability of encountering the same reconnection pattern was only 6.6%(p?=?0.012).

Conclusions

In repeat procedures PVs showed significantly more often the same reconnection pattern as during first procedure than statistically expected. More than 50% of initial isolated PVs without reconnection during adenosine testing showed a reconnection during repeat ablation. Techniques to detect susceptibility for PV re-connection like prolonged waiting-period should be applied. Elimination of DC should be expanded from segmental to circumferential re-isolation or vaster RF application.  相似文献   

2.

Background

Expert opinion recommends performing exercise testing with initiation of Class Ic antiarrhythmic medication.

Objective

To evaluate the rate and reason for discontinuation of Ic agent within the first year of follow up, with particular attention to rate of proarrhythmia and the value of routine treadmill testing.

Methods

This is a single center retrospective cohort study including consecutive patients with atrial arrhythmias who were initiated on a Class Ic agent from 2011 to 2016. Data was collated from chart review and pharmacy database.

Results

The study population included 300 patients (55% male, mean age 61; mean ejection fraction, 56%) started on flecainide (n = 153; 51%) and propafenone (n = 147; 49%). Drug initiation was completed while hospitalized on telemetry and the staff electrophysiologists directed dosing. There was one proarrhythmic event during initiation (0.3%). The primary reason for not being discharged on Ic agent was due to detection of proarrhythmia (n = 15) or ischemia (n = 1) with treadmill testing (5.3%). Exercise testing was the single significant variable to affect the decision to discontinue Ic drug, p < 0.0001 (95% CI: 1.89–6.08%). During follow up, the primary reason for discontinuation of Ic agent was lack of efficacy, 32%.

Conclusions

With proper screening, initiation of Class Ic agent is associated with very low rate of proarrhythmia. Treadmill testing is of incremental value and should be completed in all patients after loading Class Ic antiarrhythmic.  相似文献   

3.

Background

Third-generation cryoballoon (CB3) is characterized by a 40% shorter distal tip designed to increase the rate of pulmonary veins real-time signal recording in order to measure time necessary to isolate veins, the “Time to effect” (TTE). Few data are currently available on clinical follow up of CB3 treated patients.

Methods

Sixtyeight consecutive patients (mean age 57.8?±?9.6 years, 48 male) with paroxysmal or persistent atrial fibrillation (AF) were enrolled. Thirthyfour (25 paroxysmal AF) underwent to a 28 mmCB3 pulmonary veins isolation and were compared to 34 treated (21 paroxysmal AF) with 28 mmCB2.

Results

CB3 use was correlated to significant increase of the possibility to measure TTE in every treated veins (left superior 82,35% vs 23,53%, left inferior 70,59% vs 38,24%, right superior 58,82% vs 14,71%, right inferior 52,94% vs 17,65%). When it is measured, TTE wasn't different between two groups. Higher nadir temperature was observed in CB3 patients (?39.4?±?5.2?°C vs ?43.0?±?7.2?°C, p?=?0.03). CB3 procedures were shorter (91.4?±?21.7 vs 110.9?±?31.8?min, p?=?0.018), with a significant reduction in cryoenergy delivery time (24.2?±?8.5 vs 20.3?±?6.7?min, p?<?0.05), and a significant reduction in left atrium dwell time (59.3?±?9.8 vs 69.3?±?10.8?min, p?=?0.02, p?<?0.05). At one year follow up period the Kaplan-Meier curve didn't show any significant difference in AF-free survival (Log p?=?0,49).

Conclusions

Novel CB3 is a useful tool in order to simplify AF cryoballoon ablation when compared to second generation cryoballoon, as observed in our experience. Follow up data seem confirm a clinical CB3 efficacy at least comparable CB2.  相似文献   

4.

Background

Atrial tissue fibrosis can cause electrical or structural remodeling in patients with atrial fibrillation. Transforming growth factor beta 1(TGF-β1) signaling acts as a central role in fibroblast activation. In this report, we aimed to investigate the relationship between serum level of TGF-β1 and mean left atrial voltage in patients with chronic atrial fibrillation (CAF).

Methods

A total of 16 consecutive adult patients with CAF who underwent catheter ablation were enrolled. Blood samples for measurement of TGF-β1 were collected from periphery veins and coronary sinus before pulmonary vein isolation. The measurement was performed with a commercially available ELISA kit. Cardiac indices were measured using echocardiography. The left atrial electroanatomic mapping was performed after pulmonary vein isolation.

Results

Serum level of TGF-β1 in peripheral blood was higher than that in coronary sinus (p < 0.001). TGF-β1 serum level in coronary sinus negatively correlated with mean left atrial voltage (r = -0.650, p = 0.012), While periphery TGF-β1 level tended to be negatively correlated with mean left atrial voltage(r = -0.492, p = 0.053). Patients who treated with angiotensin II receptor antagonists had lower coronary sinus TGF-β1 serum level than those who did not treated with angiotensin II receptor antagonists (p = 0.046).

Conclusion

Level of TGF-β1 in peripheral serum is higher than that in coronary sinus, and serum level of TGF-β1 in coronary sinus is negatively associated with mean left atrial voltage in patients with CAF, angiotensin II receptor antagonists could affect TGF-β1 serum level.  相似文献   

5.

Objective

The decreased expression of muscle-specific microRNA-1 (miR-1) has been found in many cardiovascular diseases and is considered to contribute to heart failure (HF). Here we investigated the role of miR-1 in myocardium protection by infusion of miR-1 in a cardiac global miRNA-deficient mouse.

Methods

We generated a cardiac-selective miRNA-deficient mouse by crossing Dicerflox/flox mice with mice expressing tamoxifen-inducible Cre recombinase under the control of a mouse αMHC promoter. When Dicer gene was removed following tamoxifen injection, the mice were treated with micrONTM mmu-miR-1a-3p agomir (agomir-1). The mice were subjected to echocardiography measurement, and the heart tissue specimens were stained with hematoxylin and eosin (H&E) and Sirius red. Terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling assay and Ki67 immunofluorescence were used to determine apoptosis and proliferation.

Results

Dicer deletion resulted in extensive decrease in cardiac miRNAs in the mice. In echocardiography, the mice developed rapid and dramatic left ventricular enlargement. In histology, apparent cardiomyocyte hypertrophy, myofiber disarray, ventricular fibrosis, inflammatory infiltration, and severe ventricular remodeling were exhibited. When the mice were treated with agomir-1, they did not show any significant abnormalities in heart structure and histology in response to Dicer ablation.

Conclusion

The proper expression of miRNAs plays vital roles in the maintenance of heart histology and function. Among these miRNAs, miR-1 is critical to inhibit myocyte hypertrophy and extracellular matrix deposition, thereby preventing cardiac remodeling in cardiac-selective Dicer deficient mice.  相似文献   

6.

Background

Pacing from RV mid septum and outflow tract septum has been proposed as a more physiological site of pacing and narrower paced QRS complex duration. The paced QRS morphology and duration in different RV pacing sites is under continued discussion. Hence, this study was designed to address the correlation of pacing sites in right ventricle with paced QRS complex duration.

Methods

Two hundred fifty-two consecutive patients who underwent pacemaker implantation were enrolled. Baseline clinical characteristics were recorded for each patient. All patient underwent fluoroscopy, electrocardiogram and echocardiography post pacemaker implantation. Paced QRS duration was calculated from the leads with maximum QRS duration.

Results

Mean paced QRS (pQRS) duration was significantly higher in apical septum group with a mean of 148.9?±?14.8?m?s compared to mid septum (139.6?±?19.9?m?s; p-value 0.003) and RVOT septum (139.6?±?14.8?m?s; p-value 0.002) groups, respectively. There was no significant difference between mid-septal and RVOT septal pQRS duration. On multivariate analysis, female gender, baseline QRS duration and RVOT septal pacing were the only predictors for narrow pQRS duration (<150?msec).

Conclusion

RV mid-septal and RVOT septal pacing were associated with significantly lower pQRS duration as compared with apical pacing. Based on multivariate analysis RVOT septal pacing appears to be preferred and more physiological pacing site.  相似文献   

7.

Aims

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Patients presenting with AF are often admitted to hospital for rhythm or rate control, symptom management, and/or anticoagulation. We investigated temporal trends in AF hospitalizations in United States from 1996 to 2010.

Methods

Data were obtained from the National Hospital Discharge Survey (NHDS), a national probability sample survey of discharges conducted annually by National Center for Health Statistics. Because of the survey design, sampling weights were applied to the raw NHDS data to produce national estimates. Hospitalizations with a primary diagnosis of AF were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code of 427.31. Weighted least squares regression was used to test for linear trends in the number of AF admissions, length of stay, and inpatient mortality. We further stratified AF admissions based on patients' age, gender, and race.

Results

Admissions for a primary diagnosis of AF increased from approximately 286,000 in 1996 to about 410,000 in 2010 with a significant linear trend (β = 9470 additional admissions per year, p < 0.001). The trend of increased AF admissions was uniform across patient sub-groups. Overall, mean length of stay for AF admissions was 3.75 days, and this remained relatively stable over time (β = 0.002 days, p = 0.884). Inpatient mortality was 0.96% and also remained stable over time (β = 0.031%, p = 0.181).

Conclusion

Our data demonstrate an increase in the number of AF admissions but constant length of stay and mortality over time.  相似文献   

8.

Background

Neutrophils are known to be key players in innate immunity. Activated neutrophils induce local inflammation, which results in pathophysiologic changes during intestinal ischemia-reperfusion injury (IRI). However, most studies have been based on static assessments, and few have examined real-time intravital neutrophil recruitment. We herein report a method for imaging and evaluating dynamic changes in the neutrophil recruitment in intestinal IRI using two-photon laser scanning microscopy (TPLSM).

Methods

LysM-eGFP mice were subjected to 45?min of warm intestinal ischemia followed by reperfusion. Mice received an intravenous injection of tetramethylrhodamine isothiocyanate-labeled albumin to visualize the microvasculature. Using a time-lapse TPLSM technique, we directly observed the behavior of neutrophils in intestinal IRI.

Results

We were able to image all layers of the intestine without invasive surgical stress. At low-magnification, the number of neutrophils per field of view continued to increase for 4?h after reperfusion. High-magnification images revealed the presence or absence of blood circulation. At 0–2?h after reperfusion, rolling and adhesive neutrophils increased along the vasculature. At 2–4?h after reperfusion, the irregularity of crypt architecture and transmigration of neutrophils were observed in the lamina propria. Furthermore, TPLSM imaging revealed the villus height, the diameters of the crypt, and the number of infiltrating neutrophils in the crypt. In the IRI group, the villus height 4?h after reperfusion was significantly shorter than in the control group.

Conclusions

TPLSM imaging revealed the real-time neutrophil recruitment in intestinal IRI. Z-stack imaging was useful for evaluating pathophysiological changes in the intestinal wall.  相似文献   

9.
Many patients receiving cardiac resynchronization therapy (CRT) suffer from permanent atrial fibrillation (AF). Knowledge of the atrial rhythm is important to direct pharmacological or interventional treatment as well as maintaining AV-synchronous biventricular pacing if sinus rhythm can be restored. A single pass single-coil defibrillator lead with a floating atrial bipole has been shown to obtain reliable information about the atrial rhythm but has never been employed in a CRT-system. The purpose of this study was to assess the feasibility of implanting a single coil right ventricular ICD lead with a floating atrial bipole and the signal quality of atrial electrograms (AEGM) in CRT-defibrillator recipients with permanent AF.

Methods and results

Seventeen patients (16 males, mean age 73?±?6 years, mean EF 25?±?5%) with permanent AF and an indication for CRT-defibrillator placement were implanted with a designated CRT-D system comprising a single pass defibrillator lead with a atrial floating bipole. They were followed-up for 103?±?22 days using remote monitoring for AEGM transmission. All patients had at last one AEGM suitable for atrial rhythm diagnosis and of 100 AEGM 99% were suitable for visual atrial rhythm assessment. Four patients were discharged in sinus rhythm and one reverted to AF during follow-up.

Conclusion

Atrial electrograms retrieved from a single-pass defibrillator lead with a floating atrial bipole can be reliably used for atrial rhythm diagnosis in CRT recipients with permanent AF. Hence, a single pass ventricular defibrillator lead with a floating bipole can be considered in this population.  相似文献   

10.

Background

The prognostic significance of paced QRS complex morphology on surface ECG remains unclear. This study aimed to assess long-term outcomes associated with variations in the paced QRS complex.

Methods

Adult patients who underwent dual-chamber pacemaker implantation with 20% or more ventricular pacing and a 12-lead ECG showing a paced complex were included. The paced QRS was analyzed in leads I and aVL. Long-term clinical and echocardiographic outcomes were compared at 5 years.

Results

The study included 844 patients (43.1% female; age 75.0?±?12.1). Patients with a longer paced QRS (pQRS) duration in lead I had a lower rate of atrial fibrillation (HR 0.80; p?=?0.03) and higher rate of systolic dysfunction (HR 1.17; p?<?0.001). Total pacing complex (TPC) duration was linked to higher rates of ICD implantation (HR 1.18; p?=?0.04) and systolic dysfunction (HR 1.22, p?<?0.001). Longer paced intrinsicoid deflection (pID) was associated with less atrial fibrillation (HR 0.75; p?=?0.01), more systolic dysfunction (HR 1.17; p?<?0.001), ICD implantation (HR 1.23; p?=?0.04), and CRT upgrade (HR 1.23; p?=?0.03). Exceeding thresholds for TPC, pQRS, and pID of 170, 146, and 112?ms in lead I, respectively, was associated with a substantial increase in systolic dysfunction over 5 years (p?<?0.001).

Conclusions

Longer durations of all tested parameters in lead I were associated with increased rates of left ventricular systolic dysfunction. ICD implantation and CRT upgrade were also linked to increased TPC and pID durations. Paradoxically, patients with longer pID and pQRS had less incident atrial fibrillation.  相似文献   

11.

Aims

The aim of this study was to analyze whether local application of 3% hydrogen peroxide (H2O2) additionally to standard antibiotic prophylaxis following implantation of cardiac implantable electronic devices (CIED) reduces the incidence of pocket infections (PI).

Methods

In this observational case-control study every patient from the group additionally treated with H2O2 was matched with two patients out of the control group for age, male-gender, body-mass-index and operation time. The incidence of PI within 365 days after device implantation was compared.

Results

During the 5-year study period, 429 consecutive patients were additionally treated with H2O2 and matched with 858 patients undergoing standard treatment (mean age 69?±?12 years, 876 males (67.4%), body-mass-index 28?±?4.0?kg/m2 and operation time 45?±?23?min). Except for a more frequent use of dual-platelet-inhibition in the H2O2-group, clinical characteristics were otherwise similar. A total of 23 (1.78%) PIs occurred, most of them (14/23; 61%) during the first 45 days after implantation procedure. The use of H2O2 was associated with a significant reduction (3/429?=?0.69% versus 20/858?=?2.33%; p?=?0.04), although patients of the H2O2 treated group received more complex procedures increasing the risk of PI.

Conclusion

Intraoperative local application of 3% H2O2 seems to be associated with a significant reduced incidence of PI following implantation of CIED. Because of its non-randomized character this trial should be considered as a hypothesis generating study.  相似文献   

12.

Introduction

Posteroseptal accessory pathways account for 34.5% of the total. Of these, 36% are located within the coronary sinus (CS). Its ablation requires technical alternatives to avoid damage to surrounding tissues, especially branches of the right coronary artery.

Case report

A 22-year-old man was referred for re-do ablation of an accessory left septal-septal (PSE) pathway. Inside the CS, a precocity of 25?ms was found in the region of the median cardiac vein (VCM) (Fig. 2, panel A). Radiofrequency (RF) was administered with a non-irrigated bidirectional catheter within this vessel with resolution of the pre-excitation after 5 seconds. Immediately after, the patient presented chest pain and revealed a ST segment elevation of 1 mm in the inferior leads of ECG. Coronary angiography showed occlusion of the middle third of the posterior ventricular branch of the right coronary artery, with no signs of thrombus or dissection. Arterial angioplasty was performed with a bare metal stent, followed by TIMI III distal flow. Retrograde aortic mapping was performed and a precocity of 20?ms was found in the PSE region. The RF was applied followed by loss of pre-excitation after 1.5 seconds of application.

Conclusion

This case demonstrates the risks involving delivering radiofrequency within the coronary sinus. We discuss some strategy that could help electrophysiologists in similar cases.  相似文献   

13.

Background

Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer.

Methods

The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them.

Results

The FA-CS-DOX nano-particles were irregular and spherical particles around 30–40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway.

Conclusion

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway.  相似文献   

14.

Background

An expansion of the hexanucleotide repeat (GGGGCC)n·(GGCCCC)n in the C9orf72 promoter has been shown to be the cause of Amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). The C9orf72 repeat can form four-stranded structures; the cationic porphyrin (TMPyP4) binds and distorts these structures.

Methods

Isothermal titration calorimetry (ITC), and circular dichroism (CD) were used to study the binding of TMPyP4 to the C-rich and G-rich DNA and RNA oligos containing the hexanucleotide repeat at pH 7.5 and 0.1?M?K+.

Results

The CD spectra of G-rich DNA and RNA TMPyP4 complexes showed features of antiparallel and parallel G-quadruplexes, respectively. The shoulder at 260?nm in the CD spectrum becomes more intense upon formation of complexes between TMPyP4 and the C-rich DNA. The peak at 290?nm becomes more intense in the c-rich RNA molecules, suggesting induction of an i-motif structure. The ITC data showed that TMPyP4 binds at two independent sites for all DNA and RNA molecules.

Conclusions

For DNA, the data are consistent with TMPyP4 stacking on the terminal tetrads and intercalation. For RNA, the thermodynamics of the two binding modes are consistent with groove binding and intercalation. In both cases, intercalation is the weaker binding mode. These findings are considered with respect to the structural differences of the folded DNA and RNA molecules and the energetics of the processes that drive site-specific recognition by TMPyP4; these data will be helpful in efforts to optimize the specificity and affinity of the binding of porphyrin-like molecules.  相似文献   

15.
16.

Background

The Amigo® Remote Catheter System is a relatively new robotic system for catheter navigation. This study compared feasibility and safety using Amigo (RCM) versus manual catheter manipulation (MCM) to treat paroxysmal atrial fibrillation (PAF). Contact force (CF) and force-time integral (FTI) values obtained during pulmonary vein isolation (PVI) ablation were compared.

Methods

Forty patients were randomly selected for either RCM (20) or MCM (20). All were studied with the Thermocool® SmartTouch® force-sensing catheter (STc). Contact Force (CF), Force Time Integral (FTI) and procedure-related data, were measured/stored in the CARTO®3.

Results

All cases achieved complete PVI without major complications. Mean CF was significantly higher in the RCM group (13.3 ± 7.7 g in RCM vs. 12.04 ± 7.42 g in MCM p < 0.001), as was overall mean FTI (425.6 gs ± 199.6 gs with RCM and 407.5 gs ± 288.0 gs in MCM (p = 0.007) and was more likely to fall into the optimal FTI range (400-1000) using RCM (66.1% versus 49.1%, p < 0.001). FTI was significantly more likely to fall within the optimal range in each PV, as was CF within its optimal range in the right PVs, but trended higher in the left PVs. Freedom from atrial tachyarrhythmia was 90.0% for the RCM and 70.0% for the MCM group (p = 0,12) at 540 days follow-up.

Conclusions

This pilot study suggests that use of the Amigo RCM system, with STc catheter, seems to be safe and effective for PVI ablation in paroxysmal AF patients. A not statistically significant favorable trend was observed for RCM in term of AF-free survival.  相似文献   

17.

Background

Current algorithms and device morphology templates have been proposed in current Implantable Cardioverter-Defibrillators (ICDs) to minimize inappropriate therapies (ITS), but this has not been completely successful.

Aim

Assess the impact of a deliberate strategy of using an atrial lead implant with standardized parameters; based on all current ICD discriminators and technologies, on the burden of ITS.

Method

A retrospective single-centre analysis of 250 patients with either dual chamber (DR) ICDs or biventricular ICDs (CRTDs) over a (41.9 ± 27.3) month period was performed. The incidence of ITS on all ICD and CRTD patients was chronicled after the implementation of standardized programming.

Results

39 events of anti-tachycardial pacing (ATP) and/or shocks were identified in 20 patients (8% incidence rate among patients). The total number of individual therapies was 120, of which 34% were inappropriate ATP, and 36% were inappropriate shocks. 11 patients of the 250 patients received ITS (4.4%). Of the 20 patients, four had ICDs for primary prevention and 16 for a secondary prevention. All the episodes in the primary indication group were inappropriate, while seven patients (43%) of the secondary indication group experienced inappropriate therapies.

Conclusions

The burden of ITS in the population of patients receiving ICDs was 4.4% in the presence of atrial leads. The proposed rationalized programming criteria seems an effective strategy to minimize the burden of inappropriate therapies and will require further validation.  相似文献   

18.

Purpose

Three-dimensional retinal organoids can be differentiated from embryonic stem cells/induced pluripotent stem cells (ES/iPS cells) under defined medium conditions. We modified the serum-free floating culture of embryoid body-like aggregates with quick reaggregation (SFEBq) culture procedure to obtain retinal organoids expressing more rod photoreceptors and S- and M-cone opsins.

Methods

Retinal organoids differentiated from mouse Nrl-eGFP iPS cells were cultured in various mediums during photoreceptor development. To promote rod photoreceptor development, organoids were maintained in media containing 9-cis retinoic acids (9cRA). To obtain retinal organoids with M-opsin expression, we cultured in medium with 1% fetal bovine serum (FBS) supplemented with T3, BMP4, and DAPT. Section immunohistochemistry was performed to visualize the expression of photoreceptor markers.

Results

In three-dimensional (3D) retinas exposed to 9cRA, rhodopsin was expressed earlier and S-cone opsins were suppressed. We could maintain 3D retinas up to DD 35 in culture media with 1% FBS. The 3D retinas expressed rhodopsin, S- and M-opsins, but most cone photoreceptors expressed either S- or M-opsins.

Conclusion

By modifying culture conditions in the SFEBq protocol, we obtained rod-dominated 3D retinas and S- and M-opsin expressing 3D retinas.  相似文献   

19.

Background

Cardiomyocyte autophagy and apoptosis are crucial events underlying the development of cardiac abnormalities and dysfunction after myocardial infarction (MI). A better understanding of the cell signaling pathways involved in cardiac remodeling may support the development of new therapeutic strategies for the treatment of heart failure (HF) after MI.

Methods

A cardiac MI injury model was constructed by ligating the left anterior descending (LAD) coronary artery. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of nicorandil on MI-induced injury.

Results

Nicorandil reduced cardiac enzyme release, mitigated left ventricular enlargement and cardiac dysfunction after MI, as evaluated by echocardiography and hemodynamic measurements. According to the results of the western blot analysis and immunofluorescence staining, nicorandil enhanced autophagic flux and reduced apoptosis in cardiomyocytes subjected to hypoxic injury. Interestingly, nicorandil increased Mst1 and p-Mst1 levels in cardiomyocytes subjected to MI injury. Mst1 knockout abolished the protective effects of nicorandil on cardiac remodeling and dysfunction after MI. Mst1 knockout also abolished the beneficial effects of nicorandil on cardiac enzyme release and cardiomyocyte autophagy and apoptosis.

Conclusions

Nicorandil alleviates post-MI cardiac dysfunction and remodeling. The mechanisms were associated with enhancing autophagy and inhibiting apoptosis through Mst1 inhibition.  相似文献   

20.

Objective

Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms.

Methods

Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20?μg/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1β, and interleukin (IL)-1β in pancreatic tissue was detected by Western blot and real-time PCR.

Results

Dexmedetomidine at 20?μg/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20?μg/kg significantly down-regulated the expression of NLRP3, pro-IL-1β, and IL-1β in pancreatic tissue, but up-regulated the expression of NET in both mouse models.

Conclusion

Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号