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1.
Orphanet J Rare Dis ; 18(1): 385, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066637

RESUMO

BACKGROUND: Microcirculatory dysfunction is associated with increased morbidity and mortality in cardiac surgery patients. This study aimed to investigate the association between preoperative retinal microcirculation evaluated using optical coherence tomography angiography (OCTA) and perioperative outcomes in patients with congenital heart disease (CHD). METHODS: This prospective, observational study was performed from May 2017 to January 2021. OCTA was used to automatically quantify the vessel density (VD) of the superficial capillary plexus, deep capillary plexus (DCP), and radial peripapillary capillary (RPC) preoperatively. The primary outcome was excessive postoperative bleeding, defined as bleeding volume > 75th percentile for 24-hour postoperative chest tube output. The secondary outcome was composite adverse outcomes, including one or more operative mortalities, early postoperative complications, and prolonged length of stay. The association between retinal VD and outcomes was assessed using Poisson regression. RESULTS: In total, 173 CHD patients who underwent cardiac surgery were included (mean age, 26 years). Among them, 43 (24.9%) and 46 (26.6%) developed excessive postoperative bleeding and composite adverse outcomes, respectively. A lower VD of DCP (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.08-1.43; P = 0.003) was independently associated with excessive postoperative bleeding, and a lower VD of RPC (OR, 1.97; 95% CI, 1.08-3.57; P = 0.027), and DCP (OR, 2.17; 95% CI, 1.08-4.37; P = 0.029) were independently associated with the postoperative composite adverse outcomes. CONCLUSION: Preoperative retinal hypoperfusion was independently associated with an increased risk of perioperative adverse outcomes in patients with CHD, suggesting that retinal microcirculation evaluation could provide valuable information about the outcomes of cardiac surgery, thereby aiding physicians in tailoring individualized treatment.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Retina , Humanos , Adulto , Angiofluoresceinografia/métodos , Microcirculação , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos
2.
Front Cardiovasc Med ; 10: 1189954, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920182

RESUMO

Background: There is a lack of evidence guiding the surgical timing selection in pulmonary atresia with ventricular septal defect. This study aims to compare the long-term outcomes of different initial rehabilitative surgical ages in patients with pulmonary atresia with ventricular septal defect (PAVSD). Methods: From January 2011 to December 2020, a total of 101 PAVSD patients undergoing the initial rehabilitative surgery at our center were retrospectively reviewed. Receiver-operator characteristics curve analysis was used to identify the cutoff age of 6.4 months and therefore to classify the patients into two groups. Competing risk models were used to identify risk factors associated with complete repair. The probability of survival and complete repair were compared between the two groups using the Kaplan-Meier curve and cumulative incidence curve, respectively. Results: The median duration of follow-up was 72.76 months. There were similar ΔMcGoon ratio and ΔNakata index between the two groups. Multivariate analysis showed that age ≤6.4 months (hazard ratio (HR) = 2.728; 95% confidence interval (CI):1.122-6.637; p = 0.027) and right ventricle-to-pulmonary artery connection (HR = 4.196; 95% CI = 1.782-9.883; p = 0.001) were associated with increased probability of complete repair. The cumulative incidence curve showed that the estimated complete repair rates were 64% ± 8% after 3 years and 69% ± 8%% after 5 years in the younger group, significantly higher than 28% ± 6% after 3 years and 33% ± 6% after 5 years in the elder group (p < 0.001). There was no significant difference regarding the estimated survival rate between the two groups. Conclusion: Compared with those undergoing the initial rehabilitative surgery at the age >6.4 months, PAVSD patients at the age ≤6.4 months had an equal pulmonary vasculature development, a similar probability of survival but an improved probability of complete repair.

3.
J Cardiothorac Surg ; 18(1): 165, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37118775

RESUMO

OBJECTIVES: To analyze the epidemiological characteristics and trends in death after thoracotomy in children with congenital heart disease (CHD). METHODS: The clinical data of children with CHD aged 0-14 years who died after thoracotomy in our hospital from January 1, 2005, to December 31, 2020, were retrospectively collected to analyze the characteristics of and trends in postoperative death. RESULTS: A total of 502 patients (365 males; 72.7%) died from January 1, 2005, to December 31, 2020, with an average of 31 deaths per year. For these patients, the median age was 2.0 months, the median length of hospital stay was 16.0 days, the median postoperative time to death was 5.0 days, and the median risk adjustment in congenital heart surgery-1 (RACHS-1) score was 3.0. 29.5% underwent emergency surgery, 16.9% had postoperative ECMO support, and 15.9% received postoperative blood purification treatment. In the past 16 years, the deaths of children with CHD under 1 year old accounted for 80.5% of all deaths among children with CHD aged 0-14 years, and deaths (349 cases) under 6 kg accounted for 69.5% of all deaths. Age at death, weight, and disease type were characterized by annual changes. CONCLUSIONS: The postoperative deaths of children with CHD mainly occurred in infants and toddlers who weighed less than 6.0 kg, and TGA and PA were the most lethal CHDs. The proportion of deaths has been increasing across the years among patients who are young, have a low body weight, and have complex cyanotic CHD.


Assuntos
Cardiopatias Congênitas , Masculino , Lactente , Humanos , Estudos Retrospectivos , Cardiopatias Congênitas/cirurgia , Tempo de Internação , Hospitais , Toracotomia
4.
Circulation ; 147(11): 881-896, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36705030

RESUMO

BACKGROUND: Cardiac chamber-selective transcriptional programs underpin the structural and functional differences between atrial and ventricular cardiomyocytes (aCMs and vCMs). The mechanisms responsible for these chamber-selective transcriptional programs remain largely undefined. METHODS: We nominated candidate chamber-selective enhancers (CSEs) by determining the genome-wide occupancy of 7 key cardiac transcription factors (GATA4, MEF2A, MEF2C, NKX2-5, SRF, TBX5, TEAD1) and transcriptional coactivator P300 in atria and ventricles. Candidate enhancers were tested using an adeno-associated virus-mediated massively parallel reporter assay. Chromatin features of CSEs were evaluated by performing assay of transposase accessible chromatin sequencing and acetylation of histone H3 at lysine 27-HiChIP on aCMs and vCMs. CSE sequence requirements were determined by systematic tiling mutagenesis of 29 CSEs at 5 bp resolution. Estrogen-related receptor (ERR) function in cardiomyocytes was evaluated by Cre-loxP-mediated inactivation of ERRα and ERRγ in cardiomyocytes. RESULTS: We identified 134 066 and 97 506 regions reproducibly occupied by at least 1 transcription factor or P300, in atria or ventricles, respectively. Enhancer activities of 2639 regions bound by transcription factors or P300 were tested in aCMs and vCMs by adeno-associated virus-mediated massively parallel reporter assay. This identified 1092 active enhancers in aCMs or vCMs. Several overlapped loci associated with cardiovascular disease through genome-wide association studies, and 229 exhibited chamber-selective activity in aCMs or vCMs. Many CSEs exhibited differential chromatin accessibility between aCMs and vCMs, and CSEs were enriched for aCM- or vCM-selective acetylation of histone H3 at lysine 27-anchored loops. Tiling mutagenesis of 29 CSEs identified the binding motif of ERRα/γ as important for ventricular enhancer activity. The requirement of ERRα/γ to activate ventricular CSEs and promote vCM identity was confirmed by loss of the vCM gene profile in ERRα/γ knockout vCMs. CONCLUSIONS: We identified 229 CSEs that could be useful research tools or direct therapeutic gene expression. We showed that chamber-selective multi-transcription factor, P300 occupancy, open chromatin, and chromatin looping are predictive features of CSEs. We found that ERRα/γ are essential for maintenance of ventricular identity. Finally, our gene expression, epigenetic, 3-dimensional genome, and enhancer activity atlas provide key resources for future studies of chamber-selective gene regulation.


Assuntos
Histonas , Miócitos Cardíacos , Humanos , Miócitos Cardíacos/metabolismo , Histonas/genética , Histonas/metabolismo , Estudo de Associação Genômica Ampla , Lisina/genética , Lisina/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Cromatina/genética , Cromatina/metabolismo , Elementos Facilitadores Genéticos/genética , Estrogênios
5.
Eur J Cardiothorac Surg ; 63(4)2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36269173

RESUMO

OBJECTIVES: Transaortic myectomy is a common procedure for patients with hypertrophic obstructive cardiomyopathy. Thoracoscopic trans-mitral myectomy has been described in a few small-sample studies and has been recommended as preferable. We herein report our clinical outcomes using the thoracoscopic trans-mitral approach with 76 patients. METHODS: This is a retrospective single-centre analysis of the safety and efficacy of thoracoscopic trans-mitral myectomy by comparing the clinical outcomes with that of transaortic myectomy. RESULTS: Between April 2019 and October 2021, 132 patients underwent either a transaortic (n = 56) or a thoracoscopic trans-mitral myectomy (n = 76). Compared with those in the transaortic group, patients in the trans-mitral group were more likely to be weaned off the ventilator within 24 h after surgery (80.3% vs 60.7%, P < 0.05) and to require a shorter duration of ventilation [29.01 (43.91) vs 51.12 (94.96) h, P = 0.08] and lower transfusion rate (26.3% vs 48.2%, P < 0.05). The in-hospital mortality rate of the transaortic and trans-mitral groups was 3.6% (n = 2) and 1.3% (n = 1), respectively. No significant inter-group differences were observed regarding in-hospital mortality, the incidence of low cardiac output syndrome or permanent pacemaker implantations. In the trans-mitral group, the thickness of the interventricular septum was significantly reduced postoperatively, with resultant relief of the left ventricular outflow tract obstruction [89.37 (27.5) vs 10.51 (0.65) mmHg, P < 0.01]. Transaortic myectomy also resulted in a significant reduction in left ventricular outflow tract gradient [90.41 (33.31) vs 11.35 (9.43) mmHg, P < 0.01]. And the incidence of residual systolic anterior motion of the trans-mitral group and the transaortic group was 2.67% and 1.9%, respectively. CONCLUSIONS: The thoracoscopic trans-mitral approach provides excellent exposure to the septum and anomalies of the mitral valve and papillary muscle. It relieves obstruction effectively, without increasing the incidence of major complications.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiomiopatia Hipertrófica , Insuficiência da Valva Mitral , Septo Interventricular , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Septo Interventricular/cirurgia , Cardiomiopatia Hipertrófica/complicações , Insuficiência da Valva Mitral/cirurgia
6.
Front Cardiovasc Med ; 9: 1009165, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36578834

RESUMO

Objective: Fetal cardiopulmonary bypass (CPB) is essential to fetal heart surgery, while its development is limited by vital organ dysfunction after CPB. Studying organ metabolism may help to solve this problem. The objective of this study was to describe the tissue-specific metabolic fingerprints of fetal sheep under CPB and to associate them with organ functions. Methods: Ten pregnant ewes at 90-120 days of gestation were randomly divided into two groups. The bypass group underwent a 1-h fetal CPB, whereas the control group underwent only a fetal sternotomy. During bypass, echocardiography, blood gases, and blood biochemistry were measured. After bypass, lambs were sacrificed, and tissues of the heart, liver, brain, kidney, and placenta were harvested. The metabolites extracted from these tissues were analyzed using non-targeted metabolomics based on liquid chromatography-mass spectrometry techniques. Results: All tissues except the placenta displayed significant metabolic changes, and the fetal heart displayed obvious functional changes. Fetal sheep that underwent CPB had common and tissue-specific metabolic signatures. These changes can be attributed to dysregulated lipid metabolism, altered amino acid metabolism, and the accumulation of plasticizer metabolism. Conclusion: Fetal CPB causes tissue-specific metabolic changes in fetal sheep. Studying these metabolic changes, especially cardiac metabolism, is of great significance for the study of fetal CPB.

7.
Heart Surg Forum ; 25(5): E718-E720, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36317896

RESUMO

Extensive and serious mitral annular calcification represents a troublesome obstacle in intracardiac mitral valve replacement due to time-consuming requirements and the potential of decalcification-associated complications. We report the case of a high-risk patient with extremely severe mitral insufficiency and difficult-to-debride annular calcification who received mitral replacement using a chimney technique. This approach enabled not only the minimization of mitral calcification debridement but also the reduction of surgery time. Consequently, the surgery was successful with a great postoperative outcome. Thus, this technique is a safe and feasible option to deal with intractable mitral annular calcification during mitral valve surgery.


Assuntos
Calcinose , Cardiopatias Congênitas , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Humanos , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Calcinose/cirurgia , Cardiopatias Congênitas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Resultado do Tratamento
8.
Front Cardiovasc Med ; 9: 1023501, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337888

RESUMO

The sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly. It can develop into the heart failure if it ruptures, which requires early intervention. However, such congenital anomalies are usually treated using a median sternotomy approach. Here, we report a rare case of SVA combined with a ventricular septal defect in which the patient underwent patch repair of the defects under a total thoracoscopy approach. She was discharged uneventfully and showed no residual shunt or aortic regurgitation postoperatively or at the 12-month follow-up. The total thoracoscopic approach for SVA repair is technically feasible.

9.
Front Cardiovasc Med ; 9: 917059, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966528

RESUMO

Fontan surgery by step-wise completing the isolation of originally mixed pulmonary and systemic circulation provides an operative approach for functional single-ventricle patients not amenable to biventricular repair and allows their survival into adulthood. In the absence of a subpulmonic pumping chamber, however, the unphysiological Fontan circulation consequently results in diminished cardiac output and elevated central venous pressure, in which multiple short-term or long-term complications may develop. Current understanding of the Fontan-associated complications, particularly toward etiology and pathophysiology, is extremely incomplete. What's more, ongoing efforts have been made to manage these complications to weaken the Fontan-associated adverse impact and improve the life quality, but strategies are ill-defined. Herein, this review summarizes recent studies on cardiac and non-cardiac complications associated with Fontan circulation, focusing on significance or severity, etiology, pathophysiology, prevalence, risk factors, surveillance, or diagnosis. From the perspective of surgeons, we also discuss the management of the Fontan circulation based on current evidence, including post-operative administration of antithrombotic agents, ablation, pacemaker implantation, mechanical circulatory support, and final orthotopic heart transplantation, etc., to standardize diagnosis and treatment in the future.

10.
J Card Surg ; 37(10): 3214-3221, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35842814

RESUMO

BACKGROUND: The transaortic Morrow procedure is the current gold standard for hypertrophic obstructive cardiomyopathy (HOCM) patients who are resistant to maximum drug therapy. It is controversial whether concomitant mitral valve intervention is necessary. Only a few centers apply for concomitant anterior mitral leaflet extension with a bovine or autologous pericardial patch to further decrease systolic anterior motion. Our aim is to assess the primeval outcomes of thoracoscopic transmitral myectomy with anterior mitral leaflet extension (TTM-AMLE) in symptomatic HOCM patients. METHODS: Between April 2019 and November 2020, 18 consecutive HOCM patients who underwent TTM-AMLE were enrolled in this study. Preoperative, postoperative, and follow-up outcomes were compared and statistically analyzed. RESULTS: The mean age was (50.17 ± 6.18) years and 10 (55.56%) were males. 18 (100%) patients had mitral regurgitation preoperatively, and they all successfully underwent TTM-AMLE with a median cardiopulmonary bypass and aortic cross-clamp time of 200.0 (150.8, 232.0), and 127.5 (116.0, 149.0) min, respectively. The median length of ICU stay was 2.7 (1.4, 5.2) days. The interventricular septum thickness was significantly reduced (from 18.03 ± 3.02 mm to 11.91 ± 1.66 mm, p < .001). There was no perioperative mortality, perforation of ventricular septum, or conversion to sternotomy observed. During a median follow-up of 18 months (IQR, 5-24 months), 1 (5.56%) patient had severe mitral regurgitation due to patch detachment and received reoperation. Moderate degree of mitral regurgitation and more than 50 mmHg in left ventricular outflow tract gradient were found in 2 (11.11%), and 1 (5.56%) patients, respectively. 1 (5.56%) patient who had second-degree atrioventricular block received permanent pacemaker implantation postoperatively. Overall, the maximum left ventricular outflow tract gradient (88.50 [59.50, 112.75] mmHg vs. 10.50 [7.00, 15.50] mmHg, p = .002), left ventricular outflow tract velocity (4.70 [3.86, 5.33] m/s vs. 1.60 [1.33, 1.95] m/s, p < .001) and the degree of mitral regurgitation (6.99 ± 4.47 cm2 vs. 2.22 ± 1.51 cm2 , p = .001) were significantly decreased, with a significant reduction in the proportion of systolic anterior motion (94.44% vs. 16.67%, p < .001). CONCLUSIONS: The TTM-AMLE is a safe and effective surgical approach for selected patients with HOCM. In our series, it provides excellent relief of left ventricular outflow tract obstruction, while significantly eliminating mitral regurgitation. The early outcomes of TTM-AMLE are satisfactory, but further studies and longer follow-ups are awaited.


Assuntos
Cardiomiopatia Hipertrófica , Insuficiência da Valva Mitral , Septo Interventricular , Adulto , Animais , Cardiomiopatia Hipertrófica/complicações , Bovinos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/complicações , Resultado do Tratamento , Septo Interventricular/cirurgia
11.
Front Cardiovasc Med ; 8: 712308, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532349

RESUMO

Background: Microcirculatory changes in congenital heart disease (CHD) patients undergoing cardiac surgery are not fully understood. We aimed to investigate the changes of retinal microcirculation in CHD patients after cardiac surgery by optical coherence tomography angiography (OCTA) and explore the association between retinal microcirculation and surgical outcome. Methods: This prospective observational study consisted of 71 CHD patients aged ≥6 years undergoing cardiac surgery including 19 cyanotic CHD (CCHD) and 52 acyanotic CHD (ACHD). Optical coherence tomography angiography (OCTA) was used to measure vessel density (VD) and capillary density (CD) of radial peripapillary capillary (RPC) and peripapillary, VD of superficial capillary plexus (SCP) and deep capillary plexus (DCP), thickness of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) preoperatively and 1 month postoperatively. Transthoracic echocardiography was conducted to measure macrocirculation. Results: In CCHD patients, VD and CD of RPC and peripapillary increased postoperatively (all P < 0.05). In ACHD patients, VD of peripapillary, CD of RPC and peripapillary, and RNFL thickness increased postoperatively (all P < 0.05). VD of SCP and DCP, and GCC thickness did not change significantly in CHD patients after surgery. Lower preoperative retinal microvascular density was associated with longer cardiopulmonary bypass (CPB) time and postoperative length of stay (PLOS). No correlation was found between microcirculatory and macrohemodynamic parameters (all P > 0.05). Conclusions: Improved retinal microcirculation was observed after congenital cardiac surgery and impaired preoperative retinal microvasculature was associated with prolonged CPB time and PLOS, which might provide potential information about the outcome of congenital cardiac surgery.

12.
Comput Math Methods Med ; 2021: 6675613, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986825

RESUMO

A central shunt (CS) was an important surgery of systemic-to-pulmonary shunt (SPS) for the treatment of complex congenital heart diseases with decreased pulmonary blood flow (CCHDs-DPBF). There was no clear conclusion on how to deal with unclosed patent ductus arteriosus (PDA) during CS surgery. This study expanded the knowledge base on PDA by exploring the influence of the closing process of the PDA on the hemodynamic parameters for the CS model. The initial three-dimensional (3D) geometry was reconstructed based on the patient's computed tomography (CT) data. Then, a CS configuration with three typical pulmonary artery (PA) dysplasia structures and different sizes of PDA was established. The three-element windkessel (3WK) multiscale coupling model was used to define boundary conditions for transient simulation through computational fluid dynamics (CFD). The results showed that the larger size of PDA led to a greater systemic-to-pulmonary shunt ratio (Q S/A), and the flow ratio of the left pulmonary artery (LPA) to right pulmonary artery (RPA) (Q L/R) was more close to 1, while both the proportion of high wall shear stress (WSS) areas and power loss decreased. The case of PDA nonclosure demonstrates that the aortic oxygen saturation (Sao2) increased, while the systemic oxygen delivery (Do2) decreased. In general, for the CS model with three typical PA dysplasia, the changing trends of hemodynamic parameters during the spontaneous closing process of PDA were roughly identical, and nonclosure of PDA had a series of hemodynamic advantages, but a larger PDA may cause excessive PA perfusion and was not conducive to reducing cyanosis symptoms.


Assuntos
Permeabilidade do Canal Arterial/fisiopatologia , Permeabilidade do Canal Arterial/cirurgia , Velocidade do Fluxo Sanguíneo , Biologia Computacional , Simulação por Computador , Permeabilidade do Canal Arterial/diagnóstico por imagem , Hemodinâmica , Humanos , Imageamento Tridimensional , Recém-Nascido , Modelos Anatômicos , Modelos Cardiovasculares , Oxigênio/sangue , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/cirurgia , Atresia Pulmonar/diagnóstico por imagem , Atresia Pulmonar/fisiopatologia , Atresia Pulmonar/cirurgia , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Procedimentos Cirúrgicos Vasculares/métodos
13.
Am J Physiol Heart Circ Physiol ; 320(4): H1634-H1645, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33635162

RESUMO

Wnt/ß-catenin signaling plays a key role in pathological cardiac remodeling in adults. The identification of a tissue-specific Wnt/ß-catenin interaction factor may provide a tissue-specific clinical targeting strategy. Drosophila Pygo encodes the core interaction factor of Wnt/ß-catenin. Two Pygo homologs (Pygo1 and Pygo2) have been identified in mammals. Different from the ubiquitous expression profile of Pygo2, Pygo1 is enriched in cardiac tissue. However, the role of Pygo1 in mammalian cardiac disease is yet to be elucidated. In this study, we found that Pygo1 was upregulated in human cardiac tissues with pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy accompanied by declined cardiac function, increased heart weight/body weight and heart weight/tibial length ratios, and increased cell size. The canonical ß-catenin/T-cell transcription factor 4 (TCF4) complex was abundant in Pygo1-overexpressing transgenic (Pygo1-TG) cardiac tissue, and the downstream genes of Wnt signaling, that is, Axin2, Ephb3, and c-Myc, were upregulated. A tail vein injection of ß-catenin inhibitor effectively rescued the phenotype of cardiac failure and pathological myocardial remodeling in Pygo1-TG mice. Furthermore, in vivo downregulated pygo1 during cardiac hypertrophic condition antagonized agonist-induced cardiac hypertrophy. Therefore, our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/ß-catenin-dependent manner, which may provide new clues for tissue-specific clinical treatment via targeting this pathway.NEW & NOTEWORTHY In this study, we found that Pygo1 is associated with human pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy. Meanwhile, cardiac function was improved when expression of Pygo1 was interfered in hypertrophy-model mice. Our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/ß-catenin-dependent manner, which may provide new clues for a tissue-specific clinical treatment targeting this pathway.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Insuficiência Cardíaca/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Miocárdio/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular , Via de Sinalização Wnt , beta Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteína Axina/genética , Proteína Axina/metabolismo , Modelos Animais de Doenças , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/prevenção & controle , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/patologia , Isoproterenol , Masculino , Camundongos Transgênicos , Miocárdio/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Receptor EphB3/genética , Receptor EphB3/metabolismo , Tiazolidinas/farmacologia , Fator de Transcrição 4/genética , Fator de Transcrição 4/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/antagonistas & inibidores
14.
Ann Thorac Surg ; 111(3): e165-e168, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32777215

RESUMO

Septal myectomy is recommended for patients with hypertrophic obstructive cardiomyopathy refractory to maximal medical therapy for relieving the left ventricular outflow tract obstruction. However, poor visualization techniques and limited procedural volume restrict the progress of inexperienced surgeons performing this procedure, while inflicting minimal trauma is always clinically desirable. Therefore, this report presents a 2-port thoracoscopic septal myectomy with intuitive simulation consisting of 3-dimensional reconstruction and printing.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiomiopatia Hipertrófica/cirurgia , Septos Cardíacos/cirurgia , Impressão Tridimensional , Obstrução do Fluxo Ventricular Externo/cirurgia , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico , Ecocardiografia , Feminino , Septos Cardíacos/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Obstrução do Fluxo Ventricular Externo/diagnóstico , Obstrução do Fluxo Ventricular Externo/etiologia
15.
Biochem Soc Trans ; 48(4): 1781-1794, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32677664

RESUMO

Pygo is a nuclear protein containing two conserved domains, NHD and PHD, which play important roles in embryonic development and carcinogenesis. Pygo was first identified as a core component of the Wnt/ß-catenin signalling pathway. However, it has also been reported that the function of Pygo is not always Wnt/ß-catenin signalling dependent. In this review, we summarise the functions of both domains of Pygo and show that their functions are synergetic. The PHD domain mainly combines with transcription co-factors, including histone 3 and Bcl9/9l. The NHD domain mainly recruits histone methyltransferase/acetyltransferase (HMT/HAT) to modify lysine 4 of the histone 3 tail (H3K4) and interacts with Chip/LIM-domain DNA-binding proteins (ChiLS) to form enhanceosomes to regulate transcriptional activity. Furthermore, we summarised chromatin modification differences of Pygo in Drosophila (dPygo) and vertebrates, and found that Pygo displayes a chromatin silencing function in Drosophila, while in vertebates, Pygo has a chromatin-activating function due to the two substitution of two amino acid residues. Next, we confirmed the relationship between Pygo and Bcl9/9l and found that Pygo-Bcl/9l are specifically partnered both in the nucleus and in the cytoplasm. Finally, we discuss whether transcriptional activity of Pygo is Wnt/ß-catenin dependent during embryonic development. Available information indications that the transcriptional activity of Pygo in embryonic development is either Wnt/ß-catenin dependent or independent in both tissue-specific and cell-specific-modes.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , Animais , Proteínas de Drosophila/química , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/embriologia , Inativação Gênica/fisiologia , Histona Acetiltransferases/metabolismo , Histona Metiltransferases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Conformação Proteica , Domínios Proteicos , beta Catenina/metabolismo
16.
Eur J Cardiothorac Surg ; 57(4): 628-634, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31740945

RESUMO

OBJECTIVES: The modified extracardiac Fontan of direct total cavopulmonary connection (dTCPC) with entirely autologous vessels is a better solution in selected patients with functionally univentricular hearts because it combines the advantages of a tubular connection and of full growth potential. We investigated the mid-term to long-term outcomes of the physical condition of patients who had the dTCPC and assessed the growth potential of the autologous dTCPC pathway. METHODS: From July 2005 to June 2014, 31 patients, aged 1.8-14.0 years, underwent a modified extracardiac Fontan with dTCPC at our institution. Twenty-two patients underwent a 1-stage dTCPC and 9 patients underwent a 2-stage dTCPC. The preoperative and postoperative data were reviewed retrospectively. RESULTS: There were 17 (54.8%) boys and 14 (45.2%) girls, with a median age of 6.4 years (range 1.8-14.0 years) and a mean weight of 17.8 kg (range 9-41 kg). The mean follow-up period was 6.0 years (range 2.1-10.2 years). There was 1 early death and 2 late deaths. The event-free survival rate for the 31 patients was 88.9% at 10 years during the follow-up period. Late protein-losing enteropathy, thromboembolism, arrhythmia or heart failure were not observed. There was a significant difference between the preoperative and postoperative data for body mass index and the diameters of the autologous dTCPC pathway and pulmonary artery branches, confirming that the growth potential of the autologous dTCPC pathway was realized. CONCLUSIONS: The dTCPC procedure could be performed with satisfactory midterm to long-term outcomes in selected patients. It has the potential of retaining the advantage of the extracardiac Fontan operation together with the potential for growth and the avoidance of prosthetic materials.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Adolescente , Arritmias Cardíacas , Criança , Pré-Escolar , Feminino , Seguimentos , Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Masculino , Artéria Pulmonar/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
17.
Comput Methods Programs Biomed ; 186: 105223, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31760306

RESUMO

BACKGROUND AND OBJECTIVE: Studying the hemodynamic effects of nonclosure of patent ductus arteriosus (PDA) on the modified Blalock-Taussig shunt (MBTS) is beneficial for surgical PDA management. In the present study, the effect of PDA on MBTS was investigated numerically. A series of parameters including energy loss, wall shear stress (WSS), and left/right Pulmonary artery (LPA/RPA) flow ratio were computed from simulations to analyze the hemodynamic effects of PDA on MBTS. METHODS: To ensure the universality of the research conclusions, three typical models, including models with a well-developed RPA, a symmetrically-developed pulmonary artery(PA) and a well-developed LPA, were constructed based on patient-specific pre-surgery clinical data sets. A commercial CFD solver ANSYS-Fluent software was adopted for this study. A pressure-based solver for incompressible Newtonian flows, the K-omega based shear-stress-transport model and a second-order accurate numerical discretization scheme were employed for simulation. RESULTS: Our results show that MBTS with nonclosure of PDA is accompanied by lower blood velocity, energy loss and WSS values at the MBT shunt; smaller vortex regions; higher oxygen content(Sao2) and PA flow; and more uniform velocity distribution in the LPA and RPA than MBTS with closure of PDA. If the PDA was not closed when performing primary MBTS, a series of hemodynamic changes occurs during PDA closure in postoperative recovery: the energy loss, PA flow and Sao2 decrease, while the oxygen delivery(Do2) and WSS values at the MBT shunt increase. CONCLUSION: Nonclosure of PDA could provide a better hemodynamic environment and play an active role in preventing early acute shunt failure. It could be preferred for cases with very low PA overflow risk and may benefit patients with an underdeveloped myocardium due to its lower energy dissipation than PDA closure. However, excessive PA flow induced by nonclosure of PDA may result in a series of complications. Surgeon's decision-making process with respect to PDA management should consider the individual patient to achieve optimal postoperative recovery.


Assuntos
Procedimento de Blalock-Taussig , Permeabilidade do Canal Arterial/fisiopatologia , Hemodinâmica , Permeabilidade do Canal Arterial/cirurgia , Humanos , Recém-Nascido
18.
Ann Transl Med ; 7(14): 341, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31475211

RESUMO

BACKGROUND: To compare surgical outcomes after mitral valve replacement via either minimally invasive thoracoscopic (MIs) or traditional median sternotomy (MS) surgery and determine the short- and mid-term clinical outcomes of the MI approach. METHODS: All patients who received either MIs (n=405) or MS (n=691) mitral valve replacement surgery at the Guangdong Cardiovascular Institute between January 2012 and July 2015 were analyzed for outcome differences due to surgical approach using propensity score matching. The best 202 matches from the MI group and the MS group were analyzed. The clinical data of the two groups were collected, including preoperative cardiac function, operative data, postoperative complications, and follow-up. RESULTS: A final total of 404 patients were included in this study after propensity score matching; the MIs group and the MS group each contained 202 patients. The two groups were similar in age, weight, pathological changes, and surgical approach. Compared with the MS group, the MIs group had a longer cardiopulmonary bypass time (P<0.001), aortic cross-clamping time (P<0.001), and total procedure time (P<0.001). There were no significant differences between the groups regarding in-hospital mortality, stroke, pneumonia, acute renal failure, arrhythmia, and chylothorax. The MS group had significantly more patients with poor wound healing than the MIs group (P=0.004). The MI group had a lower rate of transfusion (P=0.037), shorter ventilation time (P=0.041), shorter ICU stay (P=0.033), reduced chest tube drainage and length of chest tube stay (P<0.001), and shorter hospital stay (P<0.001). There was no significant difference between the groups in hospital re-admission for bleeding, but the total hospitalization cost was higher in the MIs group (P=0.002). The mean follow-up was 26.59±12.33 months, the 1-year postoperative survival rate was 98.86%, and the overall survival rate was 97.44%. Compared with the MS group, the MIs group recovered earlier (P<0.05), and returned to work or study earlier (P<0.05). More patients in the MIs group were satisfied with the wound (P<0.001). The MS group had a higher incidence of postoperative osteomyelitis than the MIs group (P=0.028). There were no significant differences between groups in rates of mortality, stroke, pacemaker, reoperation, or 36-item Short Form Health Survey score. CONCLUSIONS: Compared with the MS approach, the MIs method of mitral valve replacement has longer cardiopulmonary bypass time and aortic cross-clamp time; however, it does not increase the risk of mortality and complications. Furthermore, MIs causes less trauma, fewer transfusions, less wound infection, faster recovery, faster return to work or study, and greater satisfaction with the incision in the mid-term. MI cardiac surgery is safe, effective, and feasible.

19.
J Mol Cell Cardiol ; 74: 209-19, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24887036

RESUMO

Normal high density lipoprotein (HDL) protects vascular function; however these protective effects of HDL may absent in valvular heart disease (VHD). Because vascular function plays an important role in maintaining the circulation post-cardiac surgery and some patients are difficult to stabilize, we hypothesized that a deleterious vascular effect of HDL may contribute to vascular dysfunction in VHD patients following surgery. HDL was isolated from age-match 28 healthy subjects and 84 patients with VHD and during cardiac surgery. HDL pro-inflammation index was measured and the effects of HDL on vasodilation, protein interaction, generation of nitric oxide (NO) and superoxide were determined. Patients with VHD received either simvastatin (20mg/d) or routine medications, and endothelial effects of HDL were characterized. HDL inflammation index significantly increased in VHD patients and post-cardiac surgery. HDL from VHD patients and post-cardiac surgery significantly impaired endothelium-dependent vasodilation, inhibited both Akt and endothelial nitric oxide synthase (eNOS) phosphorylation at S1177, eNOS associated with heat shock protein 90 (HSP90), NO production and increased eNOS phosphorylation at T495 and superoxide generation. Simvastatin therapy partially reduced HDL inflammation index, improved the capacity of HDL to stimulate eNOS and Akt phosphorylation at S1177, eNOS associated with HSP90, NO production, reduced eNOS phosphorylation at T495 and superoxide generation, and improved endothelium-dependent vasodilation. Our data demonstrated that HDL from VHD patients and cardiac surgery contributed to endothelial dysfunction through uncoupling of eNOS. This deleterious effect can be reversed by simvastatin, which improves the vasoprotective effects of HDL. Targeting HDL may be a therapeutic strategy for maintaining vascular function and improving the outcomes post-cardiac surgery.


Assuntos
Doenças das Valvas Cardíacas/metabolismo , Valvas Cardíacas/metabolismo , Lipoproteínas HDL/metabolismo , Adulto , Idoso , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Estudos de Casos e Controles , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Feminino , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Valvas Cardíacas/efeitos dos fármacos , Valvas Cardíacas/patologia , Humanos , Hipolipemiantes/uso terapêutico , Lipoproteínas HDL/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sinvastatina/uso terapêutico , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismo , Vasodilatação/efeitos dos fármacos
20.
J Cardiovasc Pharmacol ; 61(5): 430-6, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23429589

RESUMO

Mouse models of myocardial ischemic preconditioning (IPC) and ischemic postconditioning (IPD) have proven to be very useful models of cardiovascular diseases. In 2010, Gao described a novel procedure without the aid of mechanical ventilation. However, the technique of heart externalization could not be applied to mouse models of IPC or IPD due to the limited time frame of the technique. We proposed a modified simple and safe method using lung recruitment and short-term ventilation to perform the procedure in mice with IPC or IPD. The mice were randomly divided into 4 groups: the modified groups, M-IPC and M-IPD, and the conventional groups, C-IPC and C-IPD. In the 2 modified groups, the mice were removed from the ventilator and allowed to resume breathing spontaneously upon completion of the lung recruitment and the rapid closure of the thorax. Our study demonstrated that the postoperative recovery time was significantly reduced for the modified groups compared with the 2 conventional groups. Moreover, the inflammatory damages were attenuated by the modified method compared with the conventional method. In addition, the modified method significantly increased the survival rates of mice with IPC or IPD. The modified method improved the survival rates of mouse models of myocardial ischemia.


Assuntos
Modelos Animais de Doenças , Pós-Condicionamento Isquêmico/métodos , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/terapia , Animais , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologia , Vasos Coronários , Incidência , Interleucina-6/sangue , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/patologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
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