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OBJECTIVE: To explore the predictive value of leukocyte derived markers for postoperative delirium (POD) in patients undergoing cardiac valve surgery. METHODS: A prospective cohort study was conducted. The patients who underwent cardiac valve surgery admitted to Beijing Anzhen Hospital of Capital Medical University from October 2021 to March 2023 were enrolled. The demographic, baseline and perioperative data were collected, and the neutrophil to lymphocyte ratio (NLR) and platelet to white blood cell ratio (PWR) were calculated before operation and within 24 hours after operation. Delirium assessment was conducted twice a day for patients within 1-5 days after surgery or discharged within 5 days. According to the evaluation results, the patients were divided into delirium group and non-delirium group. The clinical indexes between the two groups were compared. Multivariate Logistic regression analysis was used to screen the independent risk factors of POD, and the POD predictive model was constructed. The predictive value of POD predictive model was evaluated by receiver operator characteristic curve (ROC curve). RESULTS: A total of 235 patients were enrolled in the analysis, of which 83 patients had POD (35.32%) and 152 patients did not have POD (64.68%). Compared with the non-delirious group, the patients in the delirious group had higher Charlson comorbidity index (CCI) score and lower mini-mental state examination (MMSE) score. In terms of perioperative data, compared with the non-delirium group, the patients in the delirium group had longer operative time, duration of cardiopulmonary bypass, length of intensive care unit (ICU) stay, duration of mechanical ventilation, and postoperative hospital stay, higher incidence of perioperative atrial fibrillation, and lower discharge life score. In terms of leukocyte derived markers, NLR within 24 hours after surgery in both groups were significantly higher than those before surgery, and PWR were significantly lower than those before surgery. The NLR within 24 hours after surgery, PWR difference and NLR difference in the delirium group were significantly higher than those in the non-delirium group. Multivariate Logistic regression analysis showed that CCI score [odds ratio (OR) = 1.394, 95% confidence interval (95%CI) was 1.038-1.872, P = 0.027], perioperative atrial fibrillation (OR = 3.697, 95%CI was 1.711-7.990, P < 0.001), duration of cardiopulmonary bypass (OR = 1.008, 95%CI was 1.002-1.015, P = 0.016), length of ICU stay (OR = 1.006, 95%CI was 1.002-1.010, P = 0.002), NLR difference (OR = 1.029, 95%CI was 1.009-1.050, P = 0.005) and PWR difference (OR = 1.044, 95%CI was 1.009-1.080, P = 0.013) were independently correlated with POD. POD predictive model was constructed by multivariate Logistic regression analysis result: POD predictive model index = -4.970+0.336×CCI score+1.317×perioperative atrial fibrillation+0.009×duration of cardiopulmonary bypass+0.006×length of ICU stay+0.030×NLR difference+0.044×PWR difference. ROC curve analysis showed that the area under the ROC curve (AUC) of NLR difference for predicting POD was 0.659 (95%CI was 0.583-0.735), the optimal critical value was 16.62, the sensitivity was 60.2%, and the specificity was 70.4% (P < 0.05). The AUC of PWR difference for predicting POD was 0.608 (95%CI was 0.528-0.688), the optimal critical value was 25.68, the sensitivity was 51.8%, and the specificity was 75.7% (P < 0.05). The AUC of POD predictive model for predicting POD was 0.805 (95%CI was 0.745-0.865), the optimal critical value was 0.39, the sensitivity was 74.7%, and the specificity was 79.6% (P < 0.05). CONCLUSIONS: The differences of NLR and PWR are independently related to POD, which has potential value in predicting POD after cardiac valve surgery.
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Biomarcadores , Delirio , Complicaciones Posoperatorias , Humanos , Delirio/diagnóstico , Delirio/etiología , Estudios Prospectivos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Biomarcadores/sangre , Factores de Riesgo , Masculino , Femenino , Válvulas Cardíacas/cirugía , Valor Predictivo de las Pruebas , Modelos Logísticos , Curva ROC , Neutrófilos , Linfocitos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Persona de Mediana Edad , LeucocitosRESUMEN
Aim: This paper investigates the conditions for inclusive design of regenerative medicine interventions from a bioethical perspective, taking regenerative valve implants as a showcase.Methods: A value hierarchy is construed to translate the value of justice into norms and design requirements for inclusive design of regenerative valve implants.Results: Three norms are proposed and translated into design requirements: regenerative valve implants should be designed to promote equal opportunity to good health for all potential users; equal respect for all potential users should be shown; and the implants should be designed to be accessible to everyone in need.Conclusion: The norms and design requirements help to design regenerative valve implants that are appropriate, respectful and available for everyone in need.
Scientists in the field of regenerative medicine are developing a new type of heart valve implant. After implantation, the synthetic implant slowly breaks down and is replaced by a new living heart valve. These so-called regenerative implants promise a complete cure. However, they also raise ethical questions. For example, questions related to justice and inclusion. In this paper, we explore how regenerative implants can be designed to be inclusive, meaning suitable, respectful and available for everyone. We argue that the design of regenerative implants should be adapted to relevant differences between users. The implants should be affordable in the short and long term. The implants should be suitable for use worldwide. The implants should be designed by teams of diverse age, gender and ethnicity. Users should be engaged in the design. And the communication about the implants to researchers and users should be inclusive. Overall, this paper provides ethical guidance to researchers and clinicians developing regenerative implants.
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Prótesis Valvulares Cardíacas , Medicina Regenerativa , Medicina Regenerativa/métodos , Humanos , Diseño de Prótesis , Válvulas CardíacasRESUMEN
Heart valve disease patients undergo multiple surgeries to replace structurally degraded valve prostheses, highlighting the need for valve replacements with growth and self-repair capacity. Given allogeneic valve transplantation's promise in meeting these goals by delivering a living valve replacement, we propose a framework for preserving and rehabilitating living valves ex vivo.
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Cardiopatías Congénitas , Prótesis Valvulares Cardíacas , Humanos , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/rehabilitación , Enfermedades de las Válvulas Cardíacas/cirugía , Enfermedades de las Válvulas Cardíacas/rehabilitación , Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodosRESUMEN
Valve remodeling is a process involving extracellular matrix organization and elongation of valve leaflets. Here, through single-cell RNA sequencing of human fetal valves, we identified an elastin-producing valve interstitial cell (VIC) subtype (apolipoprotein E (APOE)+, elastin-VICs) spatially located underneath valve endothelial cells (VECs) sensing unidirectional flow. APOE knockdown in fetal VICs resulted in profound elastogenesis defects. In valves with pulmonary stenosis (PS), we observed elastin fragmentation and decreased expression of APOE along with other genes regulating elastogenesis. Cell-cell interaction analysis revealed that jagged 1 (JAG1) from unidirectional VECs activates elastogenesis in elastin-VICs through NOTCH2. Similar observations were made in VICs cocultured with VECs under unidirectional flow. Notably, a drastic reduction of JAG1-NOTCH2 was also observed in PS valves. Lastly, we found that APOE controls JAG1-induced NOTCH activation and elastogenesis in VICs through the extracellular signal-regulated kinase pathway. Our study suggests important roles of both APOE and NOTCH in regulating elastogenesis during human valve remodeling.
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Apolipoproteínas E , Elastina , Células Endoteliales , Proteína Jagged-1 , Transducción de Señal , Humanos , Proteína Jagged-1/metabolismo , Proteína Jagged-1/genética , Elastina/metabolismo , Elastina/genética , Células Endoteliales/metabolismo , Apolipoproteínas E/metabolismo , Apolipoproteínas E/genética , Receptor Notch2/metabolismo , Receptor Notch2/genética , Células Cultivadas , Válvula Pulmonar/metabolismo , Técnicas de Cocultivo , Comunicación Celular/fisiología , Válvulas Cardíacas/embriología , Válvulas Cardíacas/metabolismoRESUMEN
BACKGROUND: Rheumatic heart disease (RHD) is an autoimmune disease caused by recurrent infections of Group A streptococcus (GAS), ultimately leading to inflammation and the fibrosis of heart valves. Recent studies have highlighted the crucial role of C-C chemokine receptor type 2-positive (CCR2+) macrophages in autoimmune diseases and tissue fibrosis. However, the specific involvement of CCR2+ macrophages in RHD remains unclear. METHODS: This study established an RHD rat model using inactivated GAS and complete Freund's adjuvant, demonstrating a correlation between CCR2+ macrophages and fibrosis in the mitral valves of these rats. RESULTS: Intraperitoneal injection of the CCR2 antagonist Rs-504393 significantly reduced macrophage infiltration, inflammation, and fibrosis in valve tissues of RHD rats compared to the solvent-treated group . Existing evidence suggests that C-C motif chemokine ligand 2 (CCL2) acts as the primary recruiting factor for CCR2+ cells. To validate this, human monocytic leukemia cells (THP-1) were cultured in vitro to assess the impact of recombinant CCL2 protein on macrophages. CCL2 exhibited pro-inflammatory effects similar to lipopolysaccharide (LPS), promoting M1 polarization in macrophages. Moreover, the combined effect of LPS and CCL2 was more potent than either alone. Knocking down CCR2 expression in THP-1 cells using small interfering RNA suppressed the pro-inflammatory response and M1 polarization induced by CCL2. CONCLUSIONS: The findings from this study indicate that CCR2+ macrophages are pivotal in the valvular remodeling process of RHD. Targeting the CCL2/CCR2 signaling pathway may therefore represent a promising therapeutic strategy to alleviate valve fibrosis in RHD.
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Inflamación , Macrófagos , Receptores CCR2 , Cardiopatía Reumática , Animales , Humanos , Masculino , Ratas , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Modelos Animales de Enfermedad , Ácido Eicosapentaenoico/análogos & derivados , Fibrosis , Válvulas Cardíacas/patología , Inflamación/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Ratas Endogámicas Lew , Receptores CCR2/metabolismo , Receptores CCR2/genética , Cardiopatía Reumática/inmunología , Cardiopatía Reumática/microbiología , Cardiopatía Reumática/metabolismo , Cardiopatía Reumática/patología , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/metabolismo , Streptococcus pyogenes , Células THP-1RESUMEN
Regenerative heart valve prostheses are essential for treating valvular heart disease, which requested interactive materials that can adapt to the tissue remodeling process. Such materials typically involves intricate designs with multiple active components, limiting their translational potential. This study introduces a facile method to engineer interactive materials for heart valve regeneration using 1,1'-thiocarbonyldiimidazole (TCDI) chemistry. TCDI crosslinking forms cleavable thiourea and thiocarbamate linkages which could gradually release H2S during degradation, therefore regulates the immune microenvironment and accelerates tissue remodeling. By employing this approach, a double network hydrogel was formed on decellularized heart valves (DHVs), showcasing robust anti-calcification and anti-thrombosis properties post fatigue testing. Post-implantation, the DHVs could adaptively degrade during recellularization, releasing H2S to further support tissue regeneration. Therefore, the comprehensive endothelial cell coverage and notable extracellular matrix remodeling could be clearly observed. This accessible and integrated strategy effectively overcomes various limitations of bioprosthetic valves, showing promise as an attractive approach for immune modulation of biomaterials.
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Prótesis Valvulares Cardíacas , Válvulas Cardíacas , Hidrogeles , Regeneración , Ingeniería de Tejidos , Hidrogeles/química , Regeneración/efectos de los fármacos , Animales , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/química , Humanos , Matriz Extracelular/metabolismo , Bioprótesis , Andamios del Tejido/química , Células Endoteliales de la Vena Umbilical Humana , Imidazoles/química , Imidazoles/farmacologíaRESUMEN
OBJECTIVES: This study aimed to analyse the impact of preoperative septic cerebral embolism on early and late postoperative outcomes in patients with infective endocarditis undergoing valve surgery. METHODS: Retrospective multicentric study based on the Clinical Multicentric Project for Analysis of Infective Endocarditis in Germany (CAMPAIGN) registry comprising patients with infective endocarditis who underwent valve surgery between 1994 and 2018 at 6 German centres. Patients were divided into 2 groups for statistical comparison according to the presence or absence of preoperative septic cerebral embolism. Propensity score matching was performed for adjusted comparisons of postoperative outcomes. Primary outcomes were 30-day mortality and estimated 5-year survival. RESULTS: A total of 4917 patients were included in the analysis, 3909 (79.5%) patients without and 1008 (20.5%) patients with preoperative septic cerebral embolism. Patients with preoperative septic cerebral embolism had more baseline comorbidities. Mitral valve endocarditis (44.1% vs 33.0% P < 0.001), large vegetations >10 mm (43.1% vs 30.0%, P < 0.001), and Staphylococcus species infection (42.3% vs 21.3%, P < 0.001) were more frequent in the cerebral embolism group. Among patients with preoperative cerebral embolism, 286 (28.4%) patients had no stroke signs (silent stroke). After matching (1008 matched pairs), there was no statistically significant difference in 30-day mortality (20.1% vs 22.8%; P = 0.14) and 5-year survival (47.8% vs 49.1%; stratified log-rank P = 0.77) in patients with and without preoperative cerebral embolism, respectively. CONCLUSIONS: Preoperative septic cerebral embolism in patients with infective endocarditis requiring valve surgery does not negatively affect early or late mortality; therefore, it should not play a major role in deciding if surgery is to be performed.
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Embolia Intracraneal , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Embolia Intracraneal/mortalidad , Embolia Intracraneal/epidemiología , Anciano , Endocarditis/cirugía , Endocarditis/mortalidad , Endocarditis/complicaciones , Alemania/epidemiología , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Sistema de Registros , Endocarditis Bacteriana/cirugía , Endocarditis Bacteriana/mortalidad , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/epidemiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/mortalidad , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Implantación de Prótesis de Válvulas Cardíacas/estadística & datos numéricos , Válvulas Cardíacas/cirugía , Factores de RiesgoRESUMEN
PURPOSE: Pediatric Cardiac Quality of Life Inventory (PCQLI) is a disease-specific pediatric cardiac health-related quality of life (HRQOL) instrument that is reliable, valid, and generalizable. We aim to demonstrate PCQLI responsiveness in children undergoing arrhythmia ablation, heart transplantation, and valve surgery before and after cardiac intervention. METHODS: Pediatric cardiac patients 8-18 years of age from 11 centers undergoing arrhythmia ablation, heart transplantation, or valve surgery were enrolled. Patient and parent-proxy PCQLI Total, Disease Impact and Psychosocial Impact subscale scores were assessed pre- and 3-12 months follow-up. Patient clinical status was assessed by a clinician post-procedure and dichotomized into markedly improved/improved and no change/worse/much worse. Paired t-tests examined change over time. RESULTS: We included 195 patient/parent-proxies: 12.6 ± 3.0 years of age; median follow-up time 6.7 (IQR = 5.3-8.2) months; procedural groups - 79 (41%) ablation, 28 (14%) heart transplantation, 88 (45%) valve surgery; clinical status - 164 (84%) markedly improved/improved, 31 (16%) no change/worse/much worse. PCQLI patient and parent-proxies Total scores increased (p ≤ 0.013) in each intervention group. All PCQLI scores were higher (p < 0.001) in the markedly improved/improved group and there were no clinically significant differences in the PCQLI scores in the no difference/worse/much worse group. CONCLUSION: The PCQLI is responsive in the pediatric cardiac population. Patients with improved clinical status and their parent-proxies reported increased HRQOL after the procedure. Patients with no improvement in clinical status and their parent-proxies reported no change in HRQOL. PCQLI may be used as a patient-reported outcome measure for longitudinal follow-up and interventional trials to assess HRQOL impact from patient and parent-proxy perspectives.
It is important to have quality of life (QOL) measures that are sensitive to change in QOL before and after procedures and to be sensitive to change over time. The Pediatric Cardiac Quality of Life Inventory (PCQLI) is a QOL measure specifically developed for children with cardiac disease. This study assessed the responsiveness of the PCQLI to detect change in QOL over time. QOL in Children and adolescents who were being treated for abnormal heart rhythms, heart transplantation, and aortic, pulmonary, or mitral valve surgery were assessed before and after their procedure. Children and adolescents with improved clinical status post-procedure, and their parents, reported better QOL after the procedure. Patients with no improvement from a cardiac standpoint and their parents reported no change in QOL after their procedure. The PCQLI may be used to assess QOL before and after cardiac procedures or medical treatment and follow QOL over time.
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Trasplante de Corazón , Calidad de Vida , Humanos , Niño , Adolescente , Trasplante de Corazón/psicología , Femenino , Masculino , Arritmias Cardíacas/psicología , Encuestas y Cuestionarios , Ablación por Catéter , Psicometría , Padres/psicología , Válvulas Cardíacas/cirugíaRESUMEN
Tissue-engineered heart valve (TEHV) has emerged as a prospective alternative to conventional valve prostheses. The decellularized heart valve (DHV) represents a promising TEHV scaffold that preserves the natural three-dimensional structure and retains essential biological activity. However, the limited mechanical strength, fast degradation, poor hemocompatibility, and lack of endothelialization of DHV restrict its clinical use, which is necessary for ensuring its long-term durability. Herein, we used oxidized chondroitin sulfate (ChS), one of the main components of the extracellular matrix with various biological activities, to cross-link DHV to overcome the above problems. In addition, the ChS-adipic dihydrazide was used to react with residual aldehyde groups, thus preventing potential calcification. The results indicated notable enhancements in mechanical properties and resilience against elastase and collagenase degradation in vitro as well as the ability to withstand extended periods of storage without compromising the structural integrity of valve scaffolds. Additionally, the newly cross-linked valves exhibited favorable hemocompatibility in vitro and in vivo, thereby demonstrating exceptional biocompatibility. Furthermore, the scaffolds exhibited traits of gradual degradation and resistance to calcification through a rat subcutaneous implantation model. In the rat abdominal aorta implantation model, the scaffolds demonstrated favorable endothelialization, commendable patency, and a diminished pro-inflammatory response. As a result, the newly constructed DHV scaffold offers a compelling alternative to traditional valve prostheses, which potentially advances the field of TEHV.
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Sulfatos de Condroitina , Animales , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Ratas , Prótesis Valvulares Cardíacas , Ingeniería de Tejidos , Válvulas Cardíacas/efectos de los fármacos , Válvulas Cardíacas/química , Ratas Sprague-Dawley , Andamios del Tejido/química , Ensayo de Materiales , Humanos , Reactivos de Enlaces Cruzados/química , Masculino , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , PorcinosRESUMEN
This meta-analysis assesses antiphospholipid antibodies' (aPLs) impact on heart valve disease in Systemic Lupus Erythematosus (SLE) patients. We searched PubMed, Embase, Cochrane, and Web of Science up to January 2024 for comparative studies of heart valve disease in aPL-positive versus aPL-negative SLE patients. Fixed-effect or random-effect models were used to synthesize data, with I2 and sensitivity analyses for heterogeneity and the trim-and-fill method for publication bias. Including 25 studies with 8089 patients, of which 919 had valvular changes, aPLs significantly increased the risk of heart valve disease (OR = 2.24, 95% CI: 1.58-3.18, p < 0.001). Lupus anticoagulant (LA) indicated the highest risk (OR = 4.90, 95% CI: 2.26-10.60, p < 0.001), anticardiolipin antibodies (aCL) doubled the risk (OR = 2.69, 95% CI: 1.47-4.93, p = 0.001), and anti-ß2 glycoprotein I (aß2GPI) showed a 70% increase (OR = 1.70, 95% CI: 1.17-2.45, p = 0.005). Valve-specific analysis indicated the mitral valve was most commonly involved (26.89%), with higher occurrences in aPL-positive patients (33.34% vs. 15.92%, p = 0.053). Aortic and tricuspid valve involvements were 13.11% vs. 5.42% (p = 0.147) and 12.03% vs. 8.52% (p = 0.039), respectively. Pulmonary valve disease was rare and similar across groups (1.01% in aPL-positive vs. 1.52% in aPL-negative). Significantly, only tricuspid valve disease showed increased risk in aPL-positive patients (OR = 2.66, 95% CI: 1.05-6.75, p = 0.039). APLs notably increase the risk of heart valve disease in SLE patients, with a pronounced effect on tricuspid valve involvement. Regular cardiac assessments for aPL-positive SLE patients are crucial for timely intervention and improved prognosis.
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Anticuerpos Antifosfolípidos , Enfermedades de las Válvulas Cardíacas , Lupus Eritematoso Sistémico , Humanos , Anticuerpos Anticardiolipina/sangre , Anticuerpos Antifosfolípidos/sangre , Enfermedades de las Válvulas Cardíacas/inmunología , Válvulas Cardíacas/patología , Inhibidor de Coagulación del Lupus/sangre , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
The gross morphological examination of native caprine heart valves revealed distinctive structural characteristics of the caprine's cardiac anatomy. Four primary orifices were identified, each protected by thin, valve-like structures. Atrioventricular orifices featured tricuspid and bicuspid valves, while the aorta and pulmonary arteries were guarded by semilunar valves. Within the atrioventricular apparatus, distinct features were observed including the tricuspid valve's three leaflets and the bicuspid valve's anterior and posterior leaflets. Ultrasonography provided insights into valve thickness and chordae tendineae lengths. Morphometric studies compared leaflets/cusps within individual native valves, showcasing significant variations in dimensions. Comparative analysis between native and decellularized valves highlighted the effects of decellularization on leaflet thickness and chordae tendineae lengths. Decellularized valves exhibited reduced dimensions compared to native valves, indicating successful removal of cellular components. While some dimensions remained unchanged post-decellularization, significant reductions were observed in leaflet thicknesses and chordae tendineae lengths. Notably, semilunar valve cusps displayed varying responses to decellularization, with significant reductions in cusp lengths observed in the aortic valve, while the pulmonary valve exhibited more subtle changes. These findings underscore the importance of understanding structural alterations in heart valves post-decellularization, providing valuable insights for tissue engineering applications and regenerative medicine.
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Cabras , Válvulas Cardíacas , Animales , Cabras/anatomía & histología , Válvulas Cardíacas/anatomía & histología , Válvula Pulmonar/anatomía & histología , Cuerdas Tendinosas/anatomía & histología , Válvula Aórtica/anatomía & histología , Válvula Tricúspide/anatomía & histología , Ultrasonografía/veterinaria , MasculinoRESUMEN
BACKGROUND: Rheumatic heart disease (RHD) is caused by inflammatory cells mistakenly attacking the heart valve due to Group A Streptococcus (GAS) infection, but it is still unclear which cells or genes are involved in the process of inflammatory cells infiltrating the valve. Inflammatory infiltration into the target tissue requires an increase in the expression of phosphorylated vascular endothelial-cadherin (p-VE-cad), p-VE-cad can increase the endothelial permeability and promote the migration of inflammatory cells across the endothelium. P-VE-cad is potentially regulated by RAS-related C3 botulinum substrate 1 (RAC1), together with phosphorylated proline-rich tyrosine kinase 2 (p-PYK2). While RAC1/p-PYK2/p-VE-cad is triggered by the activation of vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 is related to M1 macrophages adhering to the endothelium via very late antigen 4 (VLA4). Inflammatory infiltration into the valve is extremely important in the early pathogenesis of RHD. However, there is no relevant research on whether M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad is involved in RHD; therefore, what we explored in this study was whether M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad is involved. METHODS: We established a rat model of RHD and a cell model of M1 macrophage and endothelial cell cocultivation. Subsequently, we measured the degree of inflammatory cell infiltration, the levels of IL-6/IL-17, the degree of fibrosis (COL3/1), and the expression levels of fibrosis markers (FSP1, COL1A1 and COL3A1) in the heart valves of RHD rats. Additionally, we detected the expression of M1/M2 macrophage biomarkers in rat model and cell model, as well as the expression of M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad. We also tested the changes in endothelial permeability after coculturing M1 macrophages and endothelial cells. RESULTS: Compared to those in the control group, the levels of inflammatory cell infiltration and fibrotic factors in the heart valves of RHD rats were significantly higher; the expression of M1 macrophage biomarkers (iNOS, CD86 and TNF-α) in RHD rats was significantly higher; and significantly higher than the expression of M2 macrophage biomarkers (Arg1 and TGF-ß). And the expression levels of VLA4/VCAM-1 and RAC1/p-PYK2/p-VE-cad in the hearts of RHD rats were significantly higher. At the cellular level, after coculturing M1 macrophages with endothelial cells, the expression levels of VLA4/VCAM-1 and RAC1/p-PYK2/p-VE-cad were significantly higher, and the permeability of the endothelium was significantly greater due to cocultivation with M1 macrophages. CONCLUSIONS: All the results suggested that M1 macrophages and the VLA4/VCAM-1 pathway are potentially involved in the process of inflammatory infiltration in RHD.
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Macrófagos , Cardiopatía Reumática , Molécula 1 de Adhesión Celular Vascular , Animales , Cardiopatía Reumática/metabolismo , Cardiopatía Reumática/patología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Molécula 1 de Adhesión Celular Vascular/genética , Macrófagos/metabolismo , Ratas , Integrina alfa4beta1/metabolismo , Masculino , Válvulas Cardíacas/metabolismo , Válvulas Cardíacas/patología , Transducción de Señal , Ratas Sprague-Dawley , Proteína de Unión al GTP rac1/metabolismo , Modelos Animales de Enfermedad , HumanosRESUMEN
Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.
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Válvulas Cardíacas , Hidrogeles , Ratas Sprague-Dawley , Ingeniería de Tejidos , Andamios del Tejido , Ingeniería de Tejidos/métodos , Animales , Andamios del Tejido/química , Anisotropía , Ratas , Hidrogeles/química , Materiales Biocompatibles/química , Prótesis Valvulares Cardíacas , Poliésteres/química , Células Cultivadas , Humanos , Matriz Extracelular/química , MasculinoRESUMEN
BACKGROUND: Many studies have suggested that volatile anesthetic use may improve postoperative outcomes after cardiac surgery compared to total intravenous anesthesia (TIVA) owing to its potential cardioprotective effect. However, the results were inconclusive, and few studies have included patients undergoing heart valve surgery. METHODS: This nationwide population-based study included all adult patients who underwent heart valve surgery between 2010 and 2019 in Korea based on data from a health insurance claim database. Patients were divided based on the use of volatile anesthetics: the volatile anesthetics or TIVA groups. After stabilized inverse probability of treatment weighting (IPTW), the association between the use of volatile anesthetics and the risk of cumulative 1-year all-cause mortality (the primary outcome) and cumulative long-term (beyond 1 year) mortality were assessed using Cox regression analysis. RESULTS: Of the 30,755 patients included in this study, the overall incidence of 1-year mortality was 8.5%. After stabilized IPTW, the risk of cumulative 1-year mortality did not differ in the volatile anesthetics group compared to the TIVA group (hazard ratio, 0.98; 95% confidence interval, 0.90-1.07; P = .602), nor did the risk of cumulative long-term mortality (hazard ratio, 0.98; 95% confidence interval, 0.93-1.04; P = .579) at a median (interquartile range) follow-up duration of 4.8 (2.6-7.6) years. CONCLUSIONS: Compared with TIVA, volatile anesthetic use was not associated with reduced postoperative mortality risk in patients undergoing heart valve surgery. Our findings indicate that the use of volatile anesthetics does not have a significant impact on mortality after heart valve surgery. Therefore, the choice of anesthesia type can be based on the anesthesiologists' or institutional preference and experience.
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Anestesia Intravenosa , Anestésicos por Inhalación , Válvulas Cardíacas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anestesia Intravenosa/efectos adversos , Anestesia Intravenosa/mortalidad , Anciano , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/efectos adversos , República de Corea/epidemiología , Válvulas Cardíacas/cirugía , Adulto , Procedimientos Quirúrgicos Cardíacos/mortalidad , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Resultado del Tratamiento , Estudios Retrospectivos , Bases de Datos Factuales , Factores de Riesgo , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Anestesia por Inhalación/efectos adversos , Anestesia por Inhalación/mortalidad , Factores de TiempoRESUMEN
Traditional three-dimensional (3D) bioprinting has always been associated with the challenge of print fidelity of complex geometries due to the gel-like nature of the bioinks. Embedded 3D bioprinting has emerged as a potential solution to print complex geometries using proteins and polysaccharides-based bioinks. This study demonstrated the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D bioprinting method of chitosan bioink to 3D bioprint complex geometries. 4.5% chitosan was dissolved in an alkali solvent to prepare the bioink. Rheological evaluation of the bioink described its shear-thinning nature. The power law equation was fitted to the shear rate-viscosity plot. The flow index value was found to be less than 1, categorizing the material as pseudo-plastic. The chitosan bioink was extruded into another medium, a thermo-responsive 4.5% gelatin hydrogel. This hydrogel supports the growing print structures while printing. After this, the 3D bioprinted structure was crosslinked with hot water to stabilize the structure. Using this method, we have 3D bioprinted complex biological structures like the human tri-leaflet heart valve, a section of a human right coronary arterial tree, a scale-down outer structure of the human kidney, and a human ear. Additionally, we have shown the mechanical tunability and suturability of the 3D bioprinted structures. This study demonstrates the capability of the chitosan bioink and FRESH method for 3D bioprinting of complex biological models for biomedical applications.
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Bioimpresión , Quitosano , Hidrogeles , Tinta , Impresión Tridimensional , Reología , Quitosano/química , Bioimpresión/métodos , Humanos , Hidrogeles/química , Ingeniería de Tejidos/métodos , Viscosidad , Válvulas Cardíacas/fisiologíaRESUMEN
OBJECTIVES: Prolonged mechanical ventilation (PMV) is a common complication following cardiac surgery linked to unfavorable patient prognosis and increased mortality. This study aimed to search for the factors associated with the occurrence of PMV after valve surgery and to develop a risk prediction model. METHODS: The patient cohort was divided into two groups based on the presence or absence of PMV post-surgery. Comprehensive preoperative and intraoperative clinical data were collected. Univariate and multivariate logistic regression analyses were employed to identify risk factors contributing to the incidence of PMV. Based on the logistic regression results, a clinical nomogram was developed. RESULTS: The study included 550 patients who underwent valve surgery, among whom 62 (11.27%) developed PMV. Multivariate logistic regression analysis revealed that age (odds ratio [OR] = 1.082, 95% confidence interval [CI] = 1.042-1.125; P < 0.000), current smokers (OR = 1.953, 95% CI = 1.007-3.787; P = 0.047), left atrial internal diameter index (OR = 1.04, 95% CI = 1.002-1.081; P = 0.041), red blood cell count (OR = 0.49, 95% CI = 0.275-0.876; P = 0.016), and aortic clamping time (OR = 1.031, 95% CI = 1.005-1.057; P < 0.017) independently influenced the occurrence of PMV. A nomogram was constructed based on these factors. In addition, a receiver operating characteristic (ROC) curve was plotted, with an area under the curve (AUC) of 0.782 and an accuracy of 0.884. CONCLUSION: Age, current smokers, left atrial diameter index, red blood cell count, and aortic clamping time are independent risk factors for PMV in patients undergoing valve surgery. Furthermore, the nomogram based on these factors demonstrates the potential for predicting the risk of PMV in patients following valve surgery.
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Nomogramas , Valor Predictivo de las Pruebas , Respiración Artificial , Humanos , Factores de Riesgo , Masculino , Femenino , Persona de Mediana Edad , Respiración Artificial/efectos adversos , Factores de Tiempo , Medición de Riesgo , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Técnicas de Apoyo para la Decisión , Adulto , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Válvulas Cardíacas/cirugía , Enfermedades de las Válvulas Cardíacas/cirugía , Factores de EdadRESUMEN
Bacterial nanocellulose (BNC) is a promising material for heart valve prostheses. However, its low strength properties limit its applicability in cardiovascular surgery. To overcome these limitations, the mechanical properties of BNC can be improved through modifications. The aim of the research was to investigate the extent to which the mechanical properties of BNC can be altered by modifying its structure during its production and after synthesis. The study presents the results of various analyses, including tensile tests, nanoindentation tests, X-ray diffraction (XRD) tests, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR) and Raman spectroscopy, conducted on BNC chemically modified in situ with hyaluronic acid (BNC/HA) and physically modified ex situ through a dehydration/rehydration process (BNC 25DR, BNC105DR, BNC FDR and BNC/HA 25DR, BNC/HA 105DR, BNC/HA FDR). The results demonstrate that both chemical and physical modifications can effectively shape the mechanical properties of BNC. These modifications induce changes in the crystalline structure, pore size and distribution, and residual stresses of BNC. Results show the effect of the crystalline structure of BNC on its mechanical properties. There is correlation between hardness and Young's modulus and Iα/Iß index for BNC/HA and between creep rate of BNC/HA, and Young's modulus for BNC vs Iα/Iß index.