Surgical treatment of atrial fibrillation in mitral valve surgery: a narrative review.

Background and Objective: Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice, which leads to cardiac decompensation, cardiovascular and cerebrovascular infarction, and other thromboembolic diseases. AF is one of the most common comorbidities of valvular heart disease, especially in mitral valve disease. At the time of their mitral valve surgery, 20-42% of patients have AF. It is beneficial to maintain postoperative sinus rhythm and minimize complications when AF surgery is performed concurrently with mitral valve surgery. This review describes the surgical management of AF in mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. The aim of this review is to enable more patients with AF to receive more appropriate and individualised treatment. Methods: A narrative review was conducted on the literature on PubMed, Embase including all relevant studies published until November 2023. Key Content and Findings: This review focuses on the surgical management of AF during mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. Conclusions: Mitral valve surgery combined with AF surgery facilitates the maintenance of postoperative sinus rhythm in patients, reduces the risk of postoperative stroke, and improves survival. Advances in ablation technology have reduced the difficulty of the procedure, making it possible for more patients to undergo surgical ablation. In the future, it will be possible to tailor specific lesion sets and ablation modalities for individual patients. This would make surgical treatment of AF more effective and applicable to a larger population of patients with AF and mitral valve disease.

Development of neuromodulation for atrial fibrillation: a narrative review.

Background and Objective: Atrial fibrillation (AF) is a prevalent clinical arrhythmia with a high incidence of disability and mortality. Autonomic nervous system (ANS) plays a crucial role in the onset and persistence of AF, and can lead to electrophysiological changes and alterations in atrial structure. Both animal models and clinical findings suggest that parasympathetic and sympathetic activity within the cardiac ANS could induce atrial remodeling and AF. Remodeling of the cardiac autonomic nerves is a significant structural basis for promoting AF. Given the challenges faced by conventional pharmacological and atrial ablation techniques in the treatment of AF, increasing attention has been paid to autonomic intervention strategies for AF. Current research has demonstrated that the frequency and severity of AF episodes can be significantly reduced by modulating the activity of ANS. ANS neuromodulation is expected to lead more effective and personalized treatment options for patients with AF. The objective of this review is to provide a broader perspective for future related studies by reviewing preclinical and clinical studies of neuromodulation methods for the treatment of AF, searching for relevant approaches to treat AF, as well as identifying the strengths and weaknesses demonstrated by current relevant studies, and providing researchers with a broader overview of the latest neurological treatments for AF. Methods: A narrative review was conducted on the literature on PubMed, WanFang data, and Google Scholar, including all relevant studies published until November 2023. Key Content and Findings: In this review, we delve into the innervation of cardiac autonomic nerves, the role of the ANS in the development and maintenance of AF, and the current neuromodulation methods for AF treatment. These methods include stellate ganglion (SG) resection or ablation, vagus nerve stimulation (VNS), thoracic subcutaneous nerve stimulation (ScNS), renal denervation (RDN) therapy, ganglionated plexus (GP) ablation, and epicardial botulinum toxin or CaCl2 injection. More and more research suggests that neuromodulation methods for the treatment of AF have broad prospects. Conclusions: ANS plays a crucial role in AF development and maintenance through cardiac autonomic nerve remodeling. Modulating ANS activity can significantly reduce AF frequency and severity, offering more personalized treatment options. Current research on autonomic interventions for AF shows promise for more effective and personalized treatments.

Butyrate attenuates the stemness of lung cancer cells through lysosome Fe2+- and SLC7A11-mediated ferroptosis.

Cancer stem cells (CSCs) are considered key contributors to tumor progression, and ferroptosis has been identified as a potential target for CSCs. We have previously shown that butyrate enhances the ferroptosis induced by erastin in lung cancer cell, this study aimed to investigate the impact of butyrate on the progression of lung CSCs. To investigate these effects, we constructed a series of in vitro experiments, including 3D non-adherent sphere-formation, cytometry analysis, assessment of CSC marker expression, cell migration assay, and in vivo tumorigenesis analyses. Additionally, the influence of butyrate on chemotherapeutic sensitivity were determined through both in vitro and in vivo experiments. Mechanistically, immunofluorescence analysis was employed to examine the localization of biotin-conjugated butyrate. We identified that butyrate predominantly localized in the lysosome and concurrently recruited Fe2+ in lysosome. Moreover, butyrate reduced the stability of SLC7A11 protein stability in lung cancer cells through ubiquitination and proteasome degradation. Importantly, the effects of butyrate on lung CSCs were found to be dependent on lysosome Fe2+- and SLC7A11-mediated ferroptosis. In summary, our results demonstrate that butyrate could induce the ferroptosis in lung CSCs by recruiting Fe2+ in lysosome and promoting the ubiquitination-lysosome degradation of SLC7A11 protein.

Concurrent vs Staged Hybrid Ablation for Long-Standing Persistent Atrial Fibrillation: A Propensity-Matched Cohort Study.

BACKGROUND: Long-term success rates of catheter ablation (CA) for long-standing persistent atrial fibrillation (LSPAF) are less than satisfactory. Further improvement of ablation methods is crucial for enhancing the treatment of LSPAF. OBJECTIVE: This study sought to compare the outcomes of concurrent vs staged minimally invasive surgical-catheter hybrid ablation for LSPAF. METHODS: From December 2015 to December 2021, 104 matched patients (concurrent and staged, 1:1) were included in study. In the concurrent group, both left unilateral thoracoscopic epicardial ablation (EA) and CA were performed simultaneously in one procedure. In the staged group, EA was performed at the first hospitalization. If the patients experienced atrial fibrillation (AF) recurrence, CA was performed between 3 months and 1 year after EA. RESULTS: In the concurrent group, 4 patients were restored to sinus rhythm after EA, and 41 were patients restored to sinus rhythm during CA; 86.5% (45 of 52) achieved intraprocedural AF termination during concurrent hybrid ablation. In the staged group, all 52 patients underwent staged CA because of the recurrence of AF or atrial tachycardia (AT). Forty-seven (90.4%) patients achieved intraprocedural AF or AT termination during CA. Freedom from AF or AT off antiarrhythmic drugs at 2 years after hybrid ablation was 79.9% ± 5.7% in the concurrent group and 86.0% ± 4.9% in the staged group (P = 0.390). Failure of intraprocedural AF termination (HR: 14.378) was an independent risk factor for AF recurrence after hybrid ablation. CONCLUSIONS: Both concurrent and staged hybrid ablation could be safely and effectively applied to treat LSPAF. Improving the intraprocedural AF termination rate predicted better outcomes.

SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy.

Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin-like modifier (SUMO)-mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO-specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA-binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co-activator yes-associated protein 1 in the Hippo pathway. Finally, adeno-associated virus serotype 9 is used to construct TEAD1 wild-type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy-related heart failure.

Butyrate enhances erastin-induced ferroptosis of lung cancer cells via modulating the ATF3/SLC7A11 pathway.

Ferroptosis is a novel form of programmed cell death triggered by iron-dependent lipid peroxidation and has been associated with various diseases, including cancer. Erastin, an inhibitor of system Xc-, which plays a critical role in regulating ferroptosis, has been identified as an inducer of ferroptosis in cancer cells. In this study, we investigated the impact of butyrate, a short-chain fatty acid produced by gut microbiota, on erastin-induced ferroptosis in lung cancer cells. Our results demonstrated that butyrate significantly enhanced erastin-induced ferroptosis in lung cancer cells, as evidenced by increased lipid peroxidation and reduced expression of glutathione peroxidase 4 (GPX4). Mechanistically, we found that butyrate modulated the pathway involving activating transcription factor 3 (ATF3) and solute carrier family 7 member 11 (SLC7A11), leading to enhanced erastin-induced ferroptosis. Furthermore, partial reversal of the effect of butyrate on ferroptosis was observed upon knockdown of ATF3 or SLC7A11. Collectively, our findings indicate that butyrate enhances erastin-induced ferroptosis in lung cancer cells by modulating the ATF3/SLC7A11 pathway, suggesting its potential as a therapeutic agent for cancer treatment.

Enhancing percutaneous coronary intervention with heuristic path planning and deep-learning-based vascular segmentation.

Percutaneous coronary intervention (PCI) is a minimally invasive technique for treating vascular diseases. PCI requires precise and real-time visualization and guidance to ensure surgical safety and efficiency. Existing mainstream guiding methods rely on hemodynamic parameters. However, these methods are less intuitive than images and pose some challenges to the decision-making of cardiologists. This paper proposes a novel PCI guiding assistance system by combining a novel vascular segmentation network and a heuristic intervention path planning algorithm, providing cardiologists with clear and visualized information. A dataset of 1077 DSA images from 288 patients is also collected in clinical practice. A Likert Scale is also designed to evaluate system performance in user experiments. Results of user experiments demonstrate that the system can generate satisfactory and reasonable paths for PCI. Our proposed method outperformed the state-of-the-art baselines based on three metrics (Jaccard: 0.4091, F1: 0.5626, Accuracy: 0.9583). The proposed system can effectively assist cardiologists in PCI by providing a clear segmentation of vascular structures and optimal real-time intervention paths, thus demonstrating great potential for robotic PCI autonomy.

Effects and Mechanisms of Cutting Upper Thoracic Sympathetic Trunk on Ventricular Rate in Ambulatory Canines with Persistent Atrial Fibrillation.

OBJECTIVE: The purpose is to observe the effects and neural mechanism of cutting upper thoracic sympathetic trunk (TST) on the ventricular rate (VR) during persistent atrial fibrillation (AF). METHODS: Twelve beagle dogs were halving to the control group and experimental group, 6 dogs for each group. Both groups were performed with left atrial rapid pacing (600 beats/min) to induce sustained AF. The experimental group underwent cutting upper TST after a sustained AF model was established, while the control group received thoracotomy without cutting TST. Bilateral stellate ganglion (SG) and left atrial myocardium were harvested for tyrosine-hydroxylase (TH) immunohistochemical staining. RESULTS: After cutting upper TST for 30 minutes, the average VR was 121.5 ± 8.7 bpm (95% CI, 114.8 to 128.0) in the experimental group, which was significantly slower than that of the control group (144.5 ± 4.2 bpm (95% CI, 141.5 to 148.0)) (P < 0.001). After cutting upper TST for 1 month, the average VR of the experimental group (106.5 ± 4.9 bpm (95% CI, 102.0 to 110.0)) was also significantly slower versus that of the control group (139.2 ± 5.6 bpm (95% CI, 135.0 to 143.8)) (P < 0.001). Compared with the control group, both left stellate ganglion (LSG) and right stellate ganglion (RSG) of the experimental group caused neural remodeling characterized by decreased ganglionic cell density and reduced TH staining. TH-positive component was significantly decreased in the left atrium of the experimental group compared with the control group. CONCLUSIONS: Cutting upper TST could reduce fast VR during persistent AF. Cutting upper TST induced bilateral SG neural remodeling and reduced sympathetic nerve density in the left atrium, which could contribute to the underlying mechanism of VR control during AF.

MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation.

PURPOSE: Long-term failure of vein grafts due to neointimal hyperplasia remains an important problem in coronary artery bypass graft surgery. Endothelial to mesenchymal transition (EndMT) contributes to vein graft vascular remodeling. However, there is little study on microRNA-mediated EndMT contributions to neointimal formation in vein graft. We hypothesized that microRNA-92a (miR-92a) might play an important role in determining EndMT contributions to neointimal formation. METHODS: miR-92a and EndMT-related proteins detected by qRT-PCR and Western blot in vitro and in vivo. Adeno-associated virus 6 (AAV6) delivery gene therapy was used to inhibit neointimal formation in vivo. The intimal hyperplasia of vein grafts was measured by HE staining, the expression of EndMT-related protein in vein grafts was measured by immunofluorescence. Immunohistochemistry and luciferase assay were used to detect potential targets of miR-92a. RESULTS: The expression of miR-92a was found to be upregulated in neointimal hyperplasic lesions after vein grafting. Using cultured human umbilical vein endothelial cells (HUVECs), we show that TGF-ß1 treatment of HUVECs significantly increased miR-92a expression and induced EndMT, characterized by suppression of endothelial-specific markers (CD31 and VE-cadherin) and an increase in mesenchymal-specific markers (a-SMA and vimentin), while inhibition of miR-92a expression blunted EndMT in cultured HUVECs. Furthermore, AAV6 mediated miR-92a suppression gene therapy effectively resulted in decreased EndMT and less neointimal formation in vein grafts in vivo. We further identified that integrin alpha 5 (ITGA5) is a potential target gene involved in the development of neointima formation in these vein grafts. CONCLUSION: This data suggests that neointimal formation does not solely rely on vascular smooth muscle cell phenotypic switching but is also related to EndMT, and miR-92a-mediated EndMT is an important mechanism underlying neointimal formation in vein grafts.

Minimally Invasive Surgery for Hypertrophic Obstructive Cardiomyopathy With Mitral Regurgitation.

BACKGROUND: To summarize the safety and effect of minimally invasive surgery for hypertrophic obstructive cardiomyopathy (HOCM) with significant mitral regurgitation through a single transaortic approach via right minithoracotomy. METHODS: From 2008 to 2017, 51 HOCM patients with significant mitral regurgitation underwent minimally invasive surgery via right minithoracotomy. Preoperative peak left ventricular outflow tract pressure gradient (LVOTPG) was 96.53 ± 28.72 mm Hg. Preoperative average interventricular septum thickness was 24.31 ± 3.52 mm. All patients had significant mitral regurgitation with systolic anterior motion phenomenon. An oblique incision was made on the anterior wall of ascending aorta or aortic root. Modified Morrow procedure and edge-to-edge mitral valvuloplasty were performed through the single transaortic approach via right minithoracotomy. RESULTS: All patients successfully underwent the minimally invasive surgery through the single transaortic approach via right minithoracotomy. At discharge, postoperative peak LVOTPG (18.16 ± 6.41 mm Hg) and interventricular septum thickness (14.33 ± 1.99 mm) were significantly decreased compared with preoperative values (P < .05). All patients had no or trivial mitral regurgitation. The average peak mitral valve pressure gradient was 3.39 ± 1.82 mm Hg. Systolic anterior motion phenomenon disappeared in all patients. During follow-up, peak LVOTPG was 19.27 ± 6.10 mm Hg; average interventricular septum thickness was 14.67 ± 1.87 mm. All patients had no or trivial mitral regurgitation. Average peak mitral valve pressure gradient was 3.04 ± 1.52 mm Hg. No systolic anterior motion phenomenon occurred. CONCLUSIONS: Minimally invasive surgery of modified Morrow procedure and edge-to-edge mitral valvuloplasty through a single transaortic approach via right minithoracotomy could be safely and effectively applied for patients with HOCM and significant mitral regurgitation, which could also effectively eliminate systolic anterior motion phenomenon and without mitral valve stenosis.

Reverse "L" surgical approach for the management of giant tumors of the cervicothoracic junction.

BACKGROUND: An isolated cervical or thoracic surgical approach provides insufficient exposure for achieving complete resection of tumors of the cervicothoracic junction. This study examines reverse "L" thoracotomy as a surgical approach to these tumors. Additionally, the feasibility, safety, and effectiveness of reverse "L" surgical incision for tumor resection was also analyzed. METHODS: Patients with cervicothoracic tumors were identified from an internal database. Subjects were selected on the basis of undergoing reverse "L" thoracotomy from August 2014 to August 2018. The tumor characteristics, surgical technique, completeness of resection, morbidity, and patient outcome were reviewed. RESULTS: All patients successfully underwent resection through reverse "L" surgical approach. No patients needed to undergo full sternotomy. There were 6 neurogenic tumors, 4 thyroid adenocarcinomas, 4 bronchogenic tumors, and 7 other cases in the study. The median operative time was 191.0 min (range, 113.0-348.0 min) and postoperative in-hospital stay ranged from 3 to 7 days. Horner syndrome was observed in 1 case. Hoarseness and lymphatic leakage were evident in 3 and 1 case(s), respectively. Hemidiaphragm paralysis was observed in 1 case. Three cases were unsuccessful in achieving R0 resection. The duration of follow-up ranged from 6 to 42 months. Eleven of 13 patients who underwent resection had no evidence of tumor recurrence. Two patients with metastatic disease died of distant progression within 15 months. CONCLUSIONS: Applying reverse "L" surgical approach is safe, feasible, and effective for the resection of giant tumors of the cervicothoracic junction.

The Mei mini-maze procedure.

Atrial fibrillation is a common clinical arrhythmia with high morbidity and a risk of stroke. The Cox-maze IV procedure that uses radiofrequency energy for ablation is established as an effective way to eliminate atrial fibrillation. Compared to the Cox-maze IV procedure, the video-assisted Wolf mini-maze procedure is associated with reduced surgical trauma, but still requires bilateral thoracotomies, and the ablation line connecting the right and left pulmonary vein isolations cannot be created with a bipolar ablation clamp. We have developed a novel video-assisted mini-maze technique that uses a unilateral (left chest) thoracoscopic approach (the Mei mini-maze procedure).

WITHDRAWN: Detection of Atrial Fibrillation Patients and Analysis of Their Nerve and Infection Problems by CNN and Related Detection Images.

This article has been withdrawn at the request of the Editor-in-Chief. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Comparing hybrid problem-based and lecture learning (PBL + LBL) with LBL pedagogy on clinical curriculum learning for medical students in China: a meta-analysis of randomized controlled trials.

BACKGROUND: Problem-based learning (PBL) combined lecture based learning (LBL) has been a trend adopted as a new medical pedagogical approach in Chinese medical teaching. This study aims to evaluate the impacts of hybrid PBL and LBL pedagogy compared with LBL teaching method on the learning achievements of clinical curriculum for Chinese medicine students. METHODS: Randomized controlled trials (RCTs) were identified through a systematic literature search of electronic databases and article references up to June 2019. PubMed, EBSCO, Web of Science, Cochrane Library, Wanfang Database, CNKI, and China Biology Medicine database (CBM) were searched. End points included knowledge scores, skill scores, medical writing scores, comprehensive ability scores and teaching satisfaction. RESULTS: Totally 20 randomized controlled studies were finally included and all Chinese literatures, involving 1817 patients. Compared with traditional LBL pedagogy, hybrid PBL and LBL pedagogy significantly increased the clinical theoretical knowledge assessment score (RR = 4.84, 95% CI: 2.92∼6.76, P < .00001), clinical skills assessment score (RR = 1.60, 95% CI: 1.39∼1.81, P < .00001), comprehensive ability score (RR = 9.13, 95% CI: 8.42∼9.84, P < .00001) and teaching satisfaction (RR = 2.58, 95% CI: 1.84∼3.62, P < .00001), The meta-regression results showed that expertise-level of students and course type were the factors that caused heterogeneity. CONCLUSIONS: Hybrid PBL and LBL pedagogy integrates the advantages of conventional teaching methods and novel teaching methods, remarkably improves the teaching efficacy, demonstrates easy acceptance by students, and meets the demand of modern medical education, so it is an effective approach to cultivate the medical talents with an ability of innovative thinking and can be advocated and popularized as a teaching means.

Subcutaneous nerve stimulation reduces sympathetic nerve activity in ambulatory dogs with myocardial infarction.

BACKGROUND: Subcutaneous nerve stimulation (ScNS) remodels the stellate ganglion and reduces stellate ganglion nerve activity (SGNA) in dogs. Acute myocardial infarction (MI) increases SGNA through nerve sprouting. OBJECTIVE: The purpose of this study was to test the hypothesis that ScNS remodels the stellate ganglion and reduces SGNA in ambulatory dogs with acute MI. METHODS: In the experimental group, a radio transmitter was implanted during the first sterile surgery to record nerve activity and an electrocardiogram, followed by a second sterile surgery to create MI. Dogs then underwent ScNS for 2 months. The average SGNA (aSGNA) was compared with that in a historical control group (n = 9), with acute MI monitored for 2 months without ScNS. RESULTS: In the experimental group, the baseline aSGNA and heart rate were 4.08±0.35 µV and 98±12 beats/min, respectively. They increased within 1 week after MI to 6.91±1.91 µV (P=.007) and 107±10 beats/min (P=.028), respectively. ScNS reduced aSGNA to 3.46±0.44 µV (P<.039) and 2.14±0.50 µV (P<.001) at 4 and 8 weeks, respectively, after MI. In comparison, aSGNA at 4 and 8 weeks in dogs with MI but no ScNS was 8.26±6.31 µV (P=.005) and 10.82±7.86 µV (P=0002), respectively. Immunostaining showed confluent areas of remodeling in bilateral stellate ganglia and a high percentage of tyrosine hydroxylase-negative ganglion cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling was positive in 26.61%±11.54% of ganglion cells in the left stellate ganglion and 15.94%±3.62% of ganglion cells in the right stellate ganglion. CONCLUSION: ScNS remodels the stellate ganglion, reduces SGNA, and suppresses cardiac nerve sprouting after acute MI.

Left Atrial Appendage Fibrosis and 3-Year Clinical Outcomes in Atrial Fibrillation After Endoscopic Ablation: A Histologic Analysis.

BACKGROUND: Interest has been increasing in the study of atrial fibrosis, an important mechanism in atrial matrix remodeling. However, histopathologic evaluation of atrial fibrosis in non-valvular atrial fibrillation (NVAF) has been limited. This study aimed to analyze the histologic relationship between atrial fibrosis and development or recurrence of NVAF after endoscopic ablation. METHODS: Patients (n = 136) with NVAF undergoing endoscopic ablation and 10 patients in sinus rhythm were enrolled in this study. Left atrial appendage was harvested from all patients. Collagen volume fraction (CVF) and fibrosis biomarkers were evaluated. Linear regression analysis was performed to determine the correlation between clinical variables and atrial fibrosis. The association between atrial fibrosis and NVAF recurrence was evaluated with the Cox proportional hazards model. RESULTS: A significant difference was found in the degree of atrial fibrosis between patients with NVAF and sinus rhythm (CVF: median 15 [interquartile range (IQR), 13-17] vs median 6.5 [IQR, 5-10.25]; P < .001, respectively). Factors independently associated with CVF in multivariate linear regression analysis included longer duration of NVAF and larger left atrial diameter. Among 136 patients with ablation, 19 (13.9%) had recurrent NVAF. In multivariate Cox regression analysis, CVF (hazard ratio [HR] 1.093; 95% confidence interval [CI], 1.007-1.186; P = .033) and left atrial diameter (HR for 3-mm change 1.240; 95% CI, 1.004-1.531; P = .046) were independent risk factors for NVAF recurrence. CONCLUSIONS: Atrial fibrosis in NVAF is not only associated with left atrial diameter and duration of atrial fibrillation but also with recurrence after ablation. Atrial fibrosis may be a future therapeutic target for reduction of recurrence after endoscopic ablation.

Minimally Invasive Surgery for Coronary-Pulmonary Artery Fistula Via Parasternal Minithoracotomy.

Epicardial surgical repair has been proven to be effective for patients with coronary- pulmonary artery fistula (CPAF). However, most of the surgery has been performed through a median sternotomy under cardiopulmonary bypass. In this report, we describe a novel technique of performing minimally invasive surgery for CPAF patients without extracorporeal circulation via a parasternal minithoracotomy. This technique has proved to be safe and effective and may be worthy of use for patients with CPAF.

Effects of Vagal Nerve Stimulation on Ganglionated Plexi Nerve Activity and Ventricular Rate in Ambulatory Dogs With Persistent Atrial Fibrillation.

OBJECTIVES: This study was designed to test the hypothesis that low-level vagal nerve stimulation (VNS) reduces the ventricular rate (VR) during atrial fibrillation (AF) through the activation of the inferior vena cava (IVC)-inferior atrial ganglionated plexus nerve activity (IAGPNA). BACKGROUND: Increased IVC-IAGPNA can suppress atrioventricular node conduction and slow VR in canine models of AF. METHODS: Persistent AF was induced in 6 dogs and the IVC-IAGPNA, right vagal nerve activity, left vagal nerve activity, and an electrocardiogram were recorded. After persistent AF was documented, VNS was programed to 14 s "on" and 1.1 min "off." After 1 week, the VNS was reprogramed to 3 min off and stimulation continued for another week. Neural remodeling of the stellate ganglion (SG) was assessed with tyrosine hydroxylase staining and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining. RESULTS: Average IVC-IAGPNA was increased during both VNS 1.1 min off (8.20 ± 2.25 µV [95% confidence interval (CI): 6.33 to 9.53 µV]; p = 0.002) and 3 min off (7.96 ± 2.03 µV [95% CI: 6.30 to 9.27 µV]; p = 0.001) versus baseline (7.14 ± 2.20 µV [95% CI: 5.35 to 8.52 µV]). VR was reduced during both VNS 1.1 min off (123.29 ± 6.29 beats/min [95% CI: 116.69 to 129.89 beats/min]; p = 0.001) and 3 min off (120.01 ± 4.93 beats/min [95% CI: 114.84 to 125.18 beats/min]; p = 0.001) compared to baseline (142.04 ± 7.93 bpm [95% CI: 133.72 to 150.37]). Abnormal regions were observed in the left SG, but not in the right SG. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling-positive neurons were found in 22.2 ± 17.2% [95% CI: 0.9% to 43.5%] of left SG cells and 12.8 ± 8.4% [95% CI: 2.4% to 23.2%] of right SG cells. CONCLUSIONS: Chronic low-level VNS increases IVC-IAGPNA and damages bilateral stellate ganglia. Both mechanisms could contribute to the underlying mechanism of VR control during AF.

Prodigiosin Alleviates Pulmonary Fibrosis Through Inhibiting miRNA-410 and TGF-ß1/ADAMTS-1 Signaling Pathway.

BACKGROUND/AIMS: Pulmonary fibrosis is a common outcome of various interstitial lung diseases. Prodigiosin (PG) is a series of red pigment with methoxypyrrole ring. This studyinvestigates therole of prodigiosin in pulmonary fibrosis and its underlying mechanisms. METHODS: A pulmonary fibrosis rat model was established by intra-trachealinjection ofbleomycin A5. Rats were divided into 4 groups: Normal group, pulmonary fibrosis Model group, Prodigiosin treatment group and hydrocortisone treatmentgroup. HE and Masson staining were carried outto evaluate histopathological changes. The content of hydroxyproline in lung tissue was determined by alkaline hydrolysis. The expression of PICP and PIIINP was examined by ELISA. The mRNA expression of miR-410, TGF-ß1 and ADAMTS1 in lung homogenate were detected by RT-PCR. The bronchoalveolar lavage fluid (BALF) and lung tissues of rats were collected and analyzed. Human embryonic pulmonary fibroblast (HEPF) was used for study in vitro. A dual-luciferase reporter assay was conducted to examine the effect of miR-410 on ADAMTS1 expression. Cell transfection was conducted to inhibit miR-410. MTT assay was performed to investigate cell proliferation. The expressions of miR-410, TGF-ß1, ADAMTS1and other fibrosis related biomarkers (Col I, Col III, and α-SMA) wereexamined by RT-PCR and Western Blot. RESULTS: HE and Masson staining showed thickened alveolar septum, hyperplasticcapillaries, and large areas of collagen fiber deposition in pulmonary fibrosis model rats. Rats in prodigiosin and hydrocortisone treatment groups had alleviated symptoms. There was high hydroxyproline expression in model rats, whereas the expression of hydroxyproline reduced after prodigiosin or hydrocortisone treatments. RT-PCR results showed high miR-410,high TGF-ß1 and low ADAMTS1 in lung tissue of model rats. The expression of PICP and PIIINP werehigher in BALF of model group than in treatment groups. Prodigiosin and hydrocortisone treatment significantly reduced PICP and PIIINP content. RT-PCR and Western Blot analysis showed that prodigiosin inhibited expression of miR-410 and TGF-ß1, but up-regulated ADAMTS1 expression. MTT assay indicated that prodigiosin inhibited HEPF proliferation induced by miR-410 overexpression. CONCLUSION: Prodigiosin down-regulates the expression of miR-410 and TGF-ß1, up-regulates ADAMTS1, leading to decrease accumulation of fibrotic proteins. It could be used in alleviating pulmonary fibrosis.

Antiarrhythmic effects of stimulating the left dorsal branch of the thoracic nerve in a canine model of paroxysmal atrial tachyarrhythmias.

BACKGROUND: Stellate ganglion nerve activity (SGNA) precedes paroxysmal atrial tachyarrhythmia (PAT) episodes in dogs with intermittent rapid left atrial (LA) pacing. The left dorsal branch of the thoracic nerve (LDTN) contains sympathetic nerves originating from the stellate ganglia. OBJECTIVE: The purpose of this study was to test the hypothesis that high-frequency electrical stimulation of the LDTN can cause stellate ganglia damage and suppress PATs. METHODS: We performed long-term LDTN stimulation in 6 dogs with and 2 dogs without intermittent rapid LA pacing while monitoring SGNA. RESULTS: LDTN stimulation reduced average SGNA from 4.36 µV (95% confidence interval [CI] 4.10-4.62 µV) at baseline to 3.22 µV (95% CI 3.04-3.40 µV) after 2 weeks (P = .028) and completely suppressed all PAT episodes in all dogs studied. Tyrosine hydroxylase staining showed large damaged regions in both stellate ganglia, with increased percentages of tyrosine hydroxylase-negative cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that 23.36% (95% CI 18.74%-27.98%) of ganglion cells in the left stellate ganglia and 11.15% (95% CI 9.34%-12.96%) ganglion cells in the right stellate ganglia were positive, indicating extensive cell death. A reduction of both SGNA and heart rate was also observed in dogs with LDTN stimulation but without rapid LA pacing. Histological studies in the 2 dogs without intermittent rapid LA pacing confirmed the presence of extensive stellate ganglia damage, along with a high percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. CONCLUSION: LDTN stimulation damages both left and right stellate ganglia, reduces left SGNA, and is antiarrhythmic in this canine model of PAT.