Five-year follow-up after percutaneous pulmonary valve implantation using the Venus P-valve system for patients with pulmonary regurgitation and an enlarged native right ventricular outflow tract.

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) with the self-expandable Venus P-valve system is a promising treatment for patients with pulmonary regurgitation (PR) and a native right ventricular outflow tract (RVOT). However, limited data is available regarding its midterm outcomes. This study assessed the midterm clinical and echocardiographic outcomes following Venus P-valve implantation. METHODS: From 2013 to 2018, 55 patients with moderate or severe PR after surgical RVOT repair with a transannular or RVOT patch were consecutively enrolled from six hospitals in China. Five-year clinical and echocardiographic outcomes were collected and evaluated. The primary endpoint was a freedom from all-cause mortality and reintervention. RESULTS: At 5 years, the primary endpoint was met for 96% of patients, corresponding to a freedom from all-cause mortality of 96% (95% confidence interval [CI]: 86%-99%) and freedom from reintervention of 98% (95% CI: 87%-100%). Endocarditis was reported in five patients (four patients within 1 year and one patient at 5 years) following PPVI. Transpulmonary gradient and stent orifice diameter remained stable compared to at discharge (p＞0.05). No paravalvular leak was reported while only 1 patient gradually increased to moderate PR during follow-up. Significant improvement of RV diameter and LVEF (p＜0.001) sustained over the 5-year follow-up, in consistent with remarked improved New York Heart Association(NYHA) functional class (p＜0.001). CONCLUSION: The 5-year results of the China VenusP Study demonstrated the midterm benefits of Venus P-valve implantation in the management of patients with severe PR with an enlarged native RVOT by providing sustained symptomatic and hemodynamic improvement.

Whole genome sequencing in transposition of the great arteries and associations with clinically relevant heart, brain and laterality genes.

BACKGROUND: The most common cyanotic congenital heart disease (CHD) requiring management as a neonate is transposition of great arteries (TGA). Clinically, up to 50% of TGA patients develop some form of neurodevelopmental disability (NDD), thought to have a significant genetic component. A "ciliopathy" and links with laterality disorders have been proposed. This first report of whole genome sequencing in TGA, sought to identify clinically relevant variants contributing to heart, brain and laterality defects. METHODS: Initial whole genome sequencing analyses on 100 TGA patients focussed on established disease genes related to CHD (n = 107), NDD (n = 659) and heterotaxy (n = 74). Single variant as well as copy number variant analyses were conducted. Variant pathogenicity was assessed using the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines. RESULTS: Fifty-five putatively damaging variants were identified in established disease genes associated with CHD, NDD and heterotaxy; however, no clinically relevant variants could be attributed to disease. Notably, case-control analyses identified significantly more predicted-damaging, silent and total variants in TGA cases than healthy controls in established CHD genes (P < .001), NDD genes (P < .001) as well as across the three gene panels (P < .001). CONCLUSION: We present compelling evidence that the majority of TGA is not caused by monogenic rare variants and is most likely oligogenic and/or polygenic in nature, highlighting the complex genetic architecture and multifactorial influences on this CHD sub-type and its long-term sequelae. Assessment of variant burden in key heart, brain and/or laterality genes may be required to unravel the genetic contributions to TGA and related disabilities.

Secret sharing scheme based on spread spectrum ghost imaging.

(n,n) secret sharing is a procedure for splitting the key into several pieces so that no subset is sufficient to read the encrypted message except the entire one. In this paper, we propose a novel, to the best of our knowledge, secret sharing scheme based on spread spectrum ghost imaging (SSGI). In the scheme, a dealer divides a secret key, which is obtained by a modulo 2 addition over n sequences from a Hadamard matrix, into n pieces to n participants, and then the dealer uses the secret key as a direct sequence code to encrypt an image using the SSGI method. The resultant bucket signal, as the ciphertext, is then shared with n participants, and the modulated speckle patterns in SSGI are also transmitted to nparticipants by private channels for preventing eavesdropping. An independent signal is used as a protective signal to prevent the information leakage in SSGI. In the decryption process, only if all participants are honest and cooperative, the secret key can be obtained; thus, the ciphertext can be decrypted to the correct image using the second-order correlation algorithm. Otherwise, the image information cannot be extracted. The theoretical analysis shows that the probability of finding out others' pieces for successfully reconstructing the image for one dishonest participant is (1/2N)n-1, where N is the length of the secret key, and n is the number of participants. The simulation and experimental results demonstrate that the proposed scheme has a stronger data security capacity in optical information encryption.

Midterm Surgical Outcomes for ALCAPA Repair in Infants and Children.

BACKGROUND: Surgical correction of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) has been associated with excellent survival during recent years. The purpose of this study was to evaluate the effectiveness of reimplantation of the coronary artery and to investigate the recovery of postoperative cardiac and mitral valve (MV) function. METHODS: From 2005 to 2015, 80 patients who had ALCAPA received surgical correction. Among them, 49 were infants. The median patient age was 7.8 months. Operative strategies included reimplantation of the coronary artery in 71 patients, the Takeuchi procedure in another 7 patients, and coronary artery ligation in the remaining 2 patients. RESULTS: There were 11 hospital deaths and 2 late deaths. Six patients required intraoperative or postoperative mechanical circulatory support. A significant improvement in the ejection fraction (EF) and shortening fraction (SF) was present in all surviving patients at discharge, at a 3-month follow-up and at a 1-year follow-up. MV function improved gradually after surgical repair with no late secondary intervention. CONCLUSIONS: The repair of ALCAPA can be accomplished by establishment of a dual-coronary system, which offers an acceptable mortality rate and will rarely require a second surgery. Left ventricular (LV) recovery is a progressive process, especially for infants with impaired LV function. Concomitant MV annuloplasty is safe and reliable and can be performed as necessary in patients with moderate or severe mitral valve regurgitation.

Exposure to traffic-related fine particulate matter 2.5 causes respiratory damage via peroxisome proliferator-activated receptor gamma-regulated inflammation.

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation. Peroxisome proliferator-activated receptor gamma (PPARγ) has been reported to regulate inflammatory responses in diverse cell types. Therefore, this work investigated the mechanisms of PPARγ in regulating traffic-related PM2.5-induced airway inflammation. Using the diffusion flame burner soot generation, traffic-related PM2.5 was generated and adsorbed. BALB/c male mice and human bronchial epithelial cells (16-HBE) were exposed to PM2.5 alone or co-treatment with rosiglitazone (RSG), an agonist of PPARγ. To the end of exposure, bronchoalveolar lavage fluid (BALF), venous blood and arterial blood, trachea, bronchus and lung tissues were collected. The levels of IL-1ß, IL-6, and IL-17 were detected by ELISA, and the cell types in BALF were counted. Hematoxylin-eosin (H&E) assay were used to analyze the pathological conditions of lung, bronchus, and pulmonary artery. Apoptosis was detected by TUNEL, and PPARγ expression in lung and bronchus was detected by immunohistochemical (IHC) staining. Western Blot was used to detect PPARγ, NF-kB, AP-1 and STAT3 expression in lung and bronchus. The viability was detected by MTT method. PM2.5 exposure caused pathological damage to the lung, bronchus and pulmonary artery tissue, which induced apoptosis of bronchial epithelial cells. PM2.5 exposure caused local inflammation of the whole body and airway. PPARγ expression increased after PM2.5 exposure. PM2.5 exposure regulated the downstream signaling pathways to affect the inflammatory response through PPARγ. Exposure to traffic-related PM2.5 caused respiratory damage via PPARγ-regulated inflammation.

MIR3142HG promotes lipopolysaccharide-induced acute lung injury by regulating miR-450b-5p/HMGB1 axis.

The present study aimed to evaluate the potential roles of MIR3142HG, a novel long non-coding RNA (lncRNA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was simulated by the treatment of LPS in human pulmonary microvascular endothelial cells (HPMECs). The expression of MIR3142HG, miR-450b-5p and high-mobility group box 1 (HMGB1) was determined by real-time PCR and western blotting. Functional analysis was performed through the assessment of cell viability, apoptosis and the production of proinflammatory cytokines. The interactions among MIR3142HG, miR-450b-5p and HMGB1 were analyzed by bioinformatics methods, dual-luciferase reporter and RNA pull-down assays. Using gain- and loss-of-function approaches, the in vitro functions of MIR3142HG and miR-450b-5p were subsequently assessed. MIR3142HG expression was upregulated, while miR-450b-5p was decreased in LPS-treated HPMECs. MIR3142HG knockdown protected against ALI induced by LPS through alleviating the apoptosis and inflammation of HPMECs. MIR3142HG impaired miR-450b-5p-mediated inhibition of HMGB1. Besides, the effects of MIR3142HG silencing could be alleviated by miR-4262 inhibition or HMGB1 overexpression. MIR3142HG mediated LPS-induced injury of HPMECs by targeting miR-450b-5p/HMGB1, suggesting that MIR3142HG might serve as a therapeutic potential for the treatment of ALI.

Hypoxia-induced ARHGAP26 deficiency inhibits the proliferation and migration of human ductus arteriosus smooth muscle cell through activating RhoA-ROCK-PTEN pathway.

The Rho family plays crucial roles in O2 -induced vasoconstriction, cell proliferation, and migration. Rho GTPase-activating protein 26 (ARHGAP26) is a GTPase-activating protein for the small GTPases of the Rho family. Our previous studies have demonstrated that ARHGAP26 expression was significantly downregulated in patent human ductus arteriosus (DA) tissue. However, its role underlying the maintenance of DA patency is unclear. In this study, patent (fetal) and constricted (newborn) mouse DA tissues were harvested to confirm the differences in the levels of expression of ARHGAP26. Human DA smooth muscle cells (DASMCs) were isolated and cultured in vitro and used to test the function of ARHGAP26. The expression of ARHGAP26 was significantly lower in patent (fetal) than constricted (newborn) mouse DA. ARHGAP26-knocked-down human DASMCs showed reduced proliferation and migration, which are both crucial to anatomic closure of DA. Moreover, after culturing under hypoxic conditions, the expression of ARHGAP26 in human DASMCs was significantly lower and hypoxia-induced ARHGAP26 deficiency activated the phosphorylation level of phosphatase and tensin homolog (PTEN) in DASMCs by mediating the activity of RhoA and RhoA-associated kinase 1 (ROCK1). Use of Y27632, an inhibitor of ROCK which further reduces the phospholipid activity of PTEN can reverse the inhibitory effect of PTEN on the proliferation and migration of human DASMCs. This provides insight into the molecular regulation of the RhoA-ROCK-PTEN pathway in DA smooth muscle cells, which may be a suitable therapeutic target or diagnostic biomarker for perinatal DA tone management.

Total Anomalous Pulmonary Venous Connection: The Current Management Strategies in a Pediatric Cohort of 768 Patients.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease. This study describes current surgical treatment strategies and experiences in a cohort of patients from 2 congenital cardiac centers in Shanghai and Guangdong in China. METHODS: This retrospective study included 768 patients operated on between 2005 and 2014. Although most patients (n=690) underwent conventional repair, a sutureless technique was used in 10% (n=78) of cases. A multilevel mixed-effects parametric survival model and a competing-risk analysis were used to analyze associated risk factors for death and recurrent pulmonary venous obstruction (PVO), respectively. Kaplan-Meier analysis was used to analyze the overall survival. The Nelson-Aalen cumulative risk curve was used to compare distributions of time with recurrent PVO. RESULTS: The mean surgical age and weight were 214.9±39.2 days and 5.4±3.6 kg, respectively. Obstructed TAPVC (PVO) was documented in 192 (25%) of the 768 patients. There were 38 intraoperative deaths and 13 late deaths. A younger age at the time of repair (P=0.001), mixed (P=0.004) and infracardiac (P=0.035) TAPVC, preoperative PVO (P=0.027), prolonged cardiopulmonary bypass time (P<0.001), and longer duration of ventilation (P=0.028) were associated with mortality. The median follow-up was 23.2 months (range; 1-112 months). Among the 717 survivors, recurrent PVO was observed in 111 patients (15%). Associated risk factors for recurrent PVO included preoperative PVO (P<0.001), infracardiac TAPVC (P<0.001), mixed TAPVC (P=0.013), and prolonged cardiopulmonary bypass time (P<0.001). Sutureless technique was associated with a lower restenosis rate compared with conventional repair in patients with preoperative PVO (P=0.038), except in newborn patients (P=0.443). Reintervention for restenosis was performed in 24 patients. The function of most survivors (91%) was classified according to the New York Heart Association as functional class I or II. CONCLUSIONS: Surgical correction in patients with TAPVC with a biventricular anatomy can achieve an acceptable outcome. Risk factors such as a younger age at the time of repair, infracardiac and mixed TAPVC, and preoperative PVO were associated with a poorer prognosis.

Perioperative levels of total IgE correlate with outcomes of prolonged mechanical ventilation after cardiopulmonary bypass in pediatric patients.

BACKGROUND: Although cardiopulmonary bypass (CPB) has been previously studied as risking infection and inflammatory responses, few studies evaluate the relationship of preoperative high total immunoglobulin E (tIgE) to outcomes in pediatric patients predisposed to atopy undergoing cardiac surgery with CPB. METHODS: Serum tIgE, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-4, interferon-γ (IFN-γ), and T-helper type 1/2 (Th1/Th2) ratio were quantified in 104 pediatric patients who underwent surgical repair with CPB. Blood samples were obtained: before operation (T1), at the beginning (T2), and before the completion of CPB (T3), after protamine administration (T4), 4 h after CPB (T5), and on postoperative days 1 and 2 (T6, T7). Data on clinical outcomes were collected prospectively. RESULTS: Compared to 50 cases with normal tIgE, 54 cases with high tIgE were found to have higher TNF-α, IL-10, and IL-4 affected by CPB on the specific timepoints (pTNF-α < 0.001; pIL-10 = 0.035; pIL-4 = 0.001). TIgE levels shifted transiently towards Th2, which may be caused by high tIgE specific to T4. This resulted in the correlation between prolonged duration of mechanical ventilation (IL-4: r = 0.426, p = 0.015; Th1/Th2: r = -0.272, p = 0.043) in patients with high tIgE. CONCLUSIONS: A high preoperative tIgE level predisposes patients to an aggravated Th2 shift after protamine administration during CPB in association with increased risk of prolonged mechanical ventilation and medical intervention.

Outcomes of Right Ventricular Outflow Tract Reconstruction for Children with Persistent Truncus Arteriosus: A 10-Year Single-Center Experience.

The purpose of this report is to assess the mid- and long-term outcomes of right ventricular outflow tract (RVOT) reconstruction for children with persistent truncus arteriosus. Between September 2006 and 2016, 105 patients with persistent truncus arteriosus (PTA) received surgical treatment at Shanghai Children's Medical Center. Direct right ventricle-pulmonary artery anastomosis (pulmonary artery pull-down) was performed in 51 patients; a left auricle or pericardial conduit was inserted between the RVOT and pulmonary artery as a connection in 17 patients; heterograft (bovine jugular vein or Gore-tex) conduits and homograft conduits were used in 30 and 7 cases, respectively, to connect the distal pulmonary and right ventricle outflow tract; and pulmonary valve reconstruction was performed in 38 patients using a Gore-tex monocusp. There were six in-hospital deaths and one delayed death 5 months after operation. After a mean follow-up of 55.8 ± 16.5 months (6-113 months), 19 patients underwent reoperation (3 with pulmonary patch enlargement, 14 with conduit replacement and 2 with aortic valve replacement) 10-89 months after the first operation, with 1 hospital death. The actuarial survival rates were 94.2, 93.3 and 93.3% at 1, 5 and 10 years, respectively. Freedom from reoperation was 98.0, 87.8 and 82.7% at 1, 5 and 10 years, respectively. The follow-up variables included echocardiography, chest radiography, cardiac CT and cardiac function. At the last examination, most of the patients exhibited an improvement of New York Heart Association functional class from III or IV preoperatively to I or II at follow-up. Surgical treatment for PTA has an acceptable survival rate and satisfactory outcomes. Most patients exhibited an improvement in cardiac function during follow-up. Aortic arch deformity, truncal valvular regurgitation and long cardiopulmonary bypass time were regarded as risk factors for hospital mortality. Autologous tissue has a lower reoperation rate and better growth potential than extracardiac conduits. A monocusp valve effectively reduces pulmonary regurgitation in the early postoperative stage.

Efficacy of Doxycycline in the Treatment of Syphilis.

Doxycycline is an alternative antibiotic drug for the treatment of syphilis, but data on its efficacy, especially data on its efficacy against late latent syphilis, are limited. A retrospective study was conducted to evaluate the effectiveness of doxycycline for the treatment of patients with different stages of syphilis. Patients who received doxycycline treatment between June 2011 and June 2014 were involved. The serological response to doxycycline was defined as either a negative toluidine red unheated serum test (TRUST) result or a ≥4-fold decrease in titer at 12 months following the treatment. Univariate and multivariate logistic regression analyses were performed to identify factors associated with the serological response. During the study period, a total of 163 syphilis patients were treated with doxycycline, and 118 patients completed doxycycline treatment and the 12-month follow-up. Among the 118 patients, the serological response rate at 12 months was 100.0% (7/7) in patients with primary syphilis, 96.9% (62/64) in patients with secondary syphilis, 91.3% (21/23) in patients with early latent syphilis, and 79.2% (19/24) in patients with late latent syphilis. The total serological response rates were 92.4% (109/118) for preprotocol (PP) patients and 66.9% (109/163) for all intention-to-treat (ITT) patients. In multivariate analysis, patients who serologically responded at 12 months following treatment were positively associated with a higher baseline TRUST titer and an earlier syphilis stage than nonresponders. Our study showed excellent treatment outcomes in patients with different stages of syphilis. Our data, along with those from other reports, support the usage of doxycycline as a good alternative therapeutic option in the treatment of syphilis.

Anatomical Classifications of the Coronary Arteries in Complete Transposition of the Great Arteries and Double Outlet Right Ventricle with Subpulmonary Ventricular Septal Defect.

Objective To discuss the anatomical morphologies of the coronary arteries and frequencies of unusual coronary arteries in complete transposition of the great arteries and double outlet right ventricle (DORV) associated with a subpulmonic ventricular septal defect (VSD). Methods Between March 1999 and August 2012, 1,078 patients with complete transposition of the great arteries or DORV with subpulmonary VSD underwent arterial switch operations (ASOs) and were visually evaluated to classify their coronary artery morphology during open heart surgery. Results The coronary arteries could be classified into five patterns with several subtypes. Unusual coronary arteries were observed in 248 of the 1,078 cases, providing a frequency of 23.01%. The frequencies of the patients with transposition of the great arteries with intact ventricular septum (TGA/IVS), TGA/VSD, and DORV with subpulmonary VSD were 17.65, 23.28, and 31.84%, respectively. The most common morphologies were the right coronary artery (RCA) originating from sinus 1 and circumflex (CX) originating from sinus 2 (1R, AD; 2CX; 26.50%); the CX originating from sinus 2 (1AD; 2R, CX; 21.36%); the RCA, left anterior descending artery, and CX originating from single sinus 2 (2R, AD, CX; 13.24%). The in-hospital mortalities of the patients with or without unusual coronary arteries after ASO were 14.1 and 6.02%, respectively. Conclusion Patients with complete transposition of the great arteries or DORV with subpulmonary VSD have a high frequency of unusual coronary arteries, which might greatly impact on the mortality for ASO. Improving the preoperative diagnostic criteria for coronary artery morphology may significantly increase the success rate for ASOs.

Single-Stage Correction for Taussig-Bing Anomaly Associated With Aortic Arch Obstruction.

Taussig-Bing anomaly and aortic arch obstruction are two types of complex congenital cardiac malformations. Almost 50% of patients with Taussig-Bing anomaly have aortic arch obstruction. This report assesses the surgical outcomes of single-stage correction in neonates with both defects. Between November 2006 and November 2015, 39 neonates with Taussig-Bing anomaly and aortic arch obstruction (28 patients with coarctation of the aorta and 11 patients with interrupted aortic arch) underwent a one-stage arterial switch operation and aortic reconstruction. There were three in-hospital deaths and one late death (8 months after the surgery). The short-term survival rate was 92.3% (36/39), and the mid-term survival rate was 89.7% (35/39). Follow-up data were available for all patients who survived the operation (range 6-92 months). Echocardiology showed six cases of recoarctation, three cases of left ventricular outflow tract obstruction, three cases of right ventricular outflow tract obstruction, four cases of pulmonary artery stenosis, five cases of aortic regurgitation, and eight cases of pulmonary regurgitation. Eight patients required a reoperation during the follow-up period with no mortality. All survivors remained in good condition (New York Heart association functional class I or II). Single-stage correction of Taussig-Bing anomaly with aortic arch obstruction in neonates had favorable short- and mid-term outcomes in terms of mobility and reoperation rate. The optimal operative procedure should be chosen according to the position of the coronary arteries and the type of aortic anomaly.

GSK-3ß Inhibitor CHIR-99021 Promotes Proliferation Through Upregulating ß-Catenin in Neonatal Atrial Human Cardiomyocytes.

BACKGROUND: The renewal capacity of neonate human cardiomyocytes provides an opportunity to manipulate endogenous cardiogenic mechanisms for supplementing the loss of cardiomyocytes caused by myocardial infarction or other cardiac diseases. GSK-3ß inhibitors have been recently shown to promote cardiomyocyte proliferation in rats and mice, thus may be ideal candidates for inducing human cardiomyocyte proliferation. METHODS: Human cardiomyocytes were isolated from right atrial specimens obtained during routine surgery for ventricle septal defect and cultured with either GSK-3ß inhibitor (CHIR-99021) or ß-catenin inhibitor (IWR-1). Immunocytochemistry was performed to visualize 5-ethynyl-2'-deoxyuridine (EdU)-positive or Ki67-positive cardiomyocytes, indicative of proliferative cardiomyocytes. RESULTS: GSK-3ß inhibitor significantly increased ß-catenin accumulation in cell nucleus, whereas ß-catenin inhibitor significantly reduced ß-catenin accumulation in cell plasma. In parallel, GSK-3ß inhibitor increased EdU-positive and Ki67-positive cardiomyocytes, whereas ß-catenin inhibitor decreased EdU-positive and Ki67-positive cardiomyocytes. CONCLUSIONS: These results indicate that GSK-3ß inhibitor can promote human atrial cardiomyocyte proliferation. Although it remains to be determined whether the observations in atrial myocytes could be directly applicable to ventricular myocytes, the current findings imply that Wnt/ß-catenin pathway may be a valuable pathway for manipulating endogenous human heart regeneration.

Positional Relationship Between the Pulmonary Venous Confluence-Vertical Vein and Atria in Infracardiac Total Anomalous Pulmonary Venous Connection.

To explore the positional relationship between the pulmonary venous confluence-venous vein (PVC-VV) and both the atria in infracardiac total anomalous pulmonary venous connection (iTAPVC), using two-dimensional (2D) computerized tomography (CT) reconstruction. Through the 2D reconstruction of enhanced cardiac CT images of patients with iTAPVC, the projection of PVC-VV on coronal axial images was acquired and its location on the bilateral atrial splice was analyzed. Sagittal axial reconstruction was used to identify which atrium had a precise anterior-posterior positional relationship with PVC-VV. The type of iTAPVC, where the projection of PVC-VV was lying on the left atrium, and the left atrium had a precise anterior-posterior positional relationship with PVC-VV, was classified as the left atrial type. If the projection of PVC-VV was lying on the right atrium and the right atrium had a precise anterior-posterior positional relationship with PVC-VV, it was classified as the right atrial type. Finally, if the projection of PVC-VV was lying in the middle of the bilateral atria, and both the atria had precise anterior-posterior positional relationship with PVC-VV, it was referred to as the bilateral atrial type. Upon analysis of the 22 enhanced cardiac CT images, 6 were the left atrial type (27.27 %), 9 were right atrial type (40.91 %), while 7 were of the bilateral atrial type (31.82 %). The positional relationship between PVC-VV and the bilateral atria are variable, and iTAPVC classification using 2D CT reconstruction is an invaluable tool in designing the surgical approaches in iTAPVC.

Mechanical Ventilation After Bidirectional Superior Cavopulmonary Anastomosis for Single-Ventricle Physiology: A Comparison of Pressure Support Ventilation and Neurally Adjusted Ventilatory Assist.

We evaluated the effects of different respiratory assist modes on cerebral blood flow (CBF) and arterial oxygenation in single-ventricle patients after bidirectional superior cavopulmonary anastomosis (BCPA). We hypothesized that preserved auto-regulation of respiration during neurally adjusted ventilatory assist (NAVA) may have potential advantages for CBF and pulmonary blood flow regulation after the BCPA procedure. We enrolled 23 patients scheduled for BCPA, who underwent pressure-controlled ventilation (PCV), pressure support ventilation (PSV), and NAVA at two assist levels for all modes in a randomized order. PCV targeting large V T (15 mL × kg(-1)) resulted in lower CBF and oxygenation compared to targeting low V T (10 mL × kg(-1)). During PSV and NAVA, ventilation assist levels were titrated to reduce EAdi from baseline by 75 % (high assist) and 50 % (low assist). High assist levels during PSV (PSVhigh) were associated with lower PaCO2, PaO2, and O2SAT, lower CBF, and higher pulsatility index compared with those during NAVAhigh. There were no differences in parameters when using low assist levels, except for slightly greater oxygenation in the NAVAlow group. Modifying assist levels during NAVA did not influence hemodynamics, cerebral perfusion, or gas exchange. Targeting the larger V T during PCV resulted in hyperventilation, did not improve oxygenation, and was accompanied by reduced CBF. Similarly, high assist levels during PSV led to mild hyperventilation, resulting in reduced CBF. NAVA's results were independent of the assist level chosen, causing normalized PaCO2, improved oxygenation, and better CBF than did any other mode, with the exception of PSV at low assist levels.

Isobaric Tags for Relative and Absolute Quantitation-Based Proteomic Analysis of Patent and Constricted Ductus Arteriosus Tissues Confirms the Systemic Regulation of Ductus Arteriosus Closure.

We aimed to evaluate global changes in protein expression associated with patency by undertaking proteomic analysis of human constricted and patent ductus arteriosus (DA). Ten constricted and 10 patent human DAs were excised from infants with ductal-dependent heart disease during surgery. Using isobaric tags for relative and absolute quantitation-based quantitative proteomics, 132 differentially expressed proteins were identified. Of 132 proteins, voltage-gated sodium channel 1.3 (SCN3A), myosin 1d (Myo1d), Rho GTPase activating protein 26 (ARHGAP26), and retinitis pigmentosa 1 (RP1) were selected for validation by Western blot and quantitative real-time polymerase chain reaction analyses. Significant upregulation of SCN3A, Myo1d, and RP1 messenger RNA, and protein levels was observed in the patent DA group (all P ≤ 0.048). ARHGAP26 messenger RNA and protein levels were decreased in patent DA tissue (both P ≤ 0.018). Immunohistochemistry analysis revealed that Myo1d, ARHGAP26, and RP1 were specifically expressed in the subendothelial region of constricted DAs; however, diffuse expression of these proteins was noted in the patent group. Proteomic analysis revealed global changes in the expression of proteins that regulate oxygen sensing, ion channels, smooth muscle cell migration, nervous system, immune system, and metabolism, suggesting a basis for the systemic regulation of DA patency by diverse signaling pathways, which will be confirmed in further studies.

Investigation of Somatic NKX2-5 Mutations in Chinese Children with Congenital Heart Disease.

The purposes of this study are to investigate somatic NKX2-5 mutations in Chinese children with congenital heart disease (CHD) and assess the reliability of somatic mutation detection in formalin-fixed, paraffin-embedded (FFPE) tissues. The study cohort included frozen and FFPE cardiac tissues as well as blood samples from 85 Chinese children with CHD who had the cardiac operations. The right atrial appendage far from the diseased heart was used as normal control. Genomic DNA was isolated from cardiac tissues and blood samples using TIANamp Blood DNA kit. Two exons and exon-intron boundaries of NKX2-5 were amplified by polymerase chain reaction (PCR) and sequenced by dideoxynucleotide chain termination approach. The acquired sequences were aligned with GenBank sequences to identify the sequence variations. No somatic mutation in the NKX2-5 gene was observed in both frozen and FFPE cardiac tissues in 85 Chinese children with CHD. Nonetheless, a common single nucleotide polymorphism (SNP), c.63 A > G (E21E), was identified in all the three kinds of DNA samples with the same allele frequency 82.3%. Moreover, another common SNP c.606 G > C (L202L) was found in 2.3% of our patients. There were no significant differences in the allele frequencies of two SNPs between the cardiac diseased tissues and right atrial appendage (P > 0.05). PCR artefact as mutations was not found in the FFPE tissues stored for one year. Our findings demonstrate that somatic NKX2-5 mutations do not represent an important aetiologic pathway in Chinese children with congenital heart disease.

Combined Use of Etomidate and Dexmedetomidine Produces an Additive Effect in Inhibiting the Secretion of Human Adrenocortical Hormones.

BACKGROUND The direct effects of etomidate were investigated on the secretion of cortisol and its precursors by dispersed cells from the adrenal cortex of human of animals. Dexmedetomidine (DEX) is an anesthetic agent that may interfere with cortisol secretion via an unknown mechanism, such as involving inhibition of 11b-hydroxylase and the cholesterol side-chain cleavage enzyme system. The aim of this study was to determine whether dexmedetomidine (DEX) has a similar inhibitory effect on adrenocortical function, and whether combined use of etomidate (ETO) and DEX could produce a synergistic action in inhibiting the secretion of human adrenocortical hormones. MATERIAL AND METHODS Human adrenocortical cells were exposed to different concentrations of ETO and DEX. The dose-effect model between the ETO concentration and the mean secretion of cortisone (CORT) and aldosterone (ALDO) per hour was estimated. RESULTS Hill's equation well-described the dose-effect correlation between the ETO concentration and the amount of ALDO and CORT secretion. When the DEX concentration was introduced into the model by using E0 (basal secretion) as the covariate, the goodness of fit of the ETO-CORT dose-effect model was improved significantly and the objective function value was reduced by 4.55 points (P<0.05). The parameters of the final ETO-ALDO pharmacodynamics model were EC50=9.74, Emax=1.20, E0=1.33, and γ=18.5; the parameters of the final ETO-CORT pharmacodynamics model were EC50=9.49, Emax=8.16, E0=8.57, and γ=37.0. In the presence of DEX, E0 was 8.57-0.0247×(CDEX-4.6), and the other parameters remained unchanged. All parameters but γ were natural logarithm conversion values. CONCLUSIONS Combined use of DEX and ETO reduced ETO's inhibitory E0 (basal secretion) of CORT from human adrenocortical cells in a dose-dependent manner, suggesting that combined use of ETO and DEX produced an additive effect in inhibiting the secretion of human adrenocortical hormones.

Comparison of Adrenal Suppression between Etomidate and Dexmedetomidine in Children with Congenital Heart Disease.

BACKGROUND: The aim of this study was to compare plasma cortisol concentration during anesthesia of children with congenital heart disease who received dexmedetomidine (DEX) with those who received etomidate (ETO). MATERIAL AND METHODS: We recruited 99 ASA physical status II-III pediatric patients scheduled for congenital heart disease (CHD) corrective surgery and divided into them into 3 groups. Group DEX received an infusion of DEX intravenously with a bolus dose of 0.5 µg·kg-1 within 10 min during anesthesia induction, followed by a maintenance dose of DEX 0.5 µg·kg-1·h-1. Group ETO received ETO intravenously with a bolus dose of 0.3 mg·kg-1 without a maintenance dose. Group CON received routine anesthetics as controls. The preset timepoints were: before anesthesia induction (T0), at the end of induction (T1), 30 min after anesthesia induction (T2), at the time of aortic and inferior vena catheterization (T3), and at 180 min (T4) and 24 h (T5) after anesthesia induction. RESULTS: The cortisol concentration decreased gradually after anesthesia induction in all groups, and returned to baseline values after 24 h. The cortisol concentration was significantly lower in Group ETO children than in Group DEX or group CON at T4. CONCLUSIONS: The plasma concentrations of cortisol decreased in CHD children after the operation, but returned to baseline after 24 h of anesthesia induction. The adrenal cortex function inhibition induced by ETO in CHD children is longer and more serious than that induced by DEX (if any) during the preoperative period.