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1.
Echocardiography ; 41(9): e15923, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39254118

RESUMEN

Inferior sinus venosus atrial septal defect (SVASD) is the rarest form of the atrial septal defect (ASD) and can sometimes go unnoticed. Although this defect can be associated with other congenital anomalies, its association with hypoplasia of the posterior mitral leaflet is extremely rare. In this case, we present a woman with a history of surgery for an ostium secundum ASD who exhibited persistent right heart chamber dilation. Echocardiography revealed hypoplasia of the posterior mitral leaflet, and cardiac magnetic resonance (CMR) imaging confirmed the presence of a previously undetected inferior sinus venosus ASD.


Asunto(s)
Defectos del Tabique Interatrial , Válvula Mitral , Humanos , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico , Defectos del Tabique Interatrial/diagnóstico por imagen , Femenino , Válvula Mitral/anomalías , Válvula Mitral/diagnóstico por imagen , Ecocardiografía/métodos
3.
Artículo en Inglés | MEDLINE | ID: mdl-39243264

RESUMEN

BACKGROUND: Tricuspid regurgitation (TR) is a common valve disease that has a significant impact on patients' quality of life. OBJECTIVES: This study sought to report the final 3-year outcomes of tricuspid transcatheter edge-to-edge repair (T-TEER) with the TriClip (Abbott) implant from the TRILUMINATE (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR) study for the treatment of severe symptomatic TR. METHODS: The TRILUMINATE study (N = 98 subjects) is an international, prospective, single-arm, multicenter study to investigate the safety and performance of T-TEER with the TriClip implant in patients with symptomatic moderate or greater TR. Echocardiographic assessments were performed at a core laboratory. RESULTS: At 3 years, TR was reduced to moderate or less in 79% of subjects, and a reduction of at least 1 grade was achieved in 92% of subjects. TR reduction achieved at 1 year was sustained through 3 years. Subjects also experienced an improvement in heart failure symptoms assessed by NYHA functional class and quality of life assessed by the Kansas City Cardiomyopathy Questionnaire at 3 years compared to baseline. The site-reported heart failure hospitalization rate decreased from 0.43 events/patient-year 1 year before device implantation to 0.06 events/patient-year 1 year after device implantation, representing a reduction of 86% (P < 0.0001). CONCLUSIONS: In the longest follow-up to date of any T-TEER therapy, the TRILUMINATE study demonstrated that the TriClip procedure is both safe and effective, with sustained benefits at 3 years in subjects with symptomatic moderate or greater TR. (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR [TRILUMINATE]; NCT03227757).

6.
JACC Cardiovasc Interv ; 17(17): 2023-2037, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39260960

RESUMEN

BACKGROUND: Research on the role of transcatheter heart valve (THV) deformation and calcium distribution in patients with bicuspid aortic valves (BAVs) undergoing transcatheter aortic valve replacement (TAVR) remains limited. OBJECTIVES: The aim of this study was to evaluate the impact of THV deformation on clinical outcomes in individuals with BAVs undergoing TAVR and the influence of calcium on these outcomes. METHODS: In total, 229 consecutive patients with BAVs who underwent TAVR with balloon-expandable valves and had computed tomography (CT) performed 30 days post-TAVR were analyzed. Patients were stratified into 3 groups: group 1 (n = 125), with no THV underexpansion or eccentricity; group 2 (n = 69), with underexpansion or eccentricity; and group 3 (n = 35), with both. Calcium distribution was assessed using CT, and its associations with clinical outcomes, including all-cause mortality at 3 years and leaflet thrombosis at 30 days, were determined. A subgroup analysis of patients with type 1 BAVs was conducted. RESULTS: Group 3 exhibited higher rates of all-cause mortality than the other groups, along with the highest risk for hypoattenuated leaflet thickening at 30 days. Multivariate analysis identified annular and left ventricular outflow tract calcification as independent predictors of all-cause mortality and hypoattenuated leaflet thickening. In patients with type 1 BAVs, excessive calcification at the raphe and opposite leaflet were associated with all-cause mortality at 3 years. CONCLUSIONS: THV deformation post-TAVR was significantly linked to all-cause mortality in patients with BAVs. Annular and left ventricular outflow tract calcification correlated with increased risks for all-cause mortality and leaflet thrombosis. (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment With Anticoagulation [RESOLVE]; NCT02318342).


Asunto(s)
Estenosis de la Válvula Aórtica , Válvula Aórtica , Valvuloplastia con Balón , Enfermedad de la Válvula Aórtica Bicúspide , Calcinosis , Enfermedades de las Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Diseño de Prótesis , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Masculino , Femenino , Enfermedad de la Válvula Aórtica Bicúspide/diagnóstico por imagen , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Reemplazo de la Válvula Aórtica Transcatéter/instrumentación , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Válvula Aórtica/fisiopatología , Válvula Aórtica/anomalías , Resultado del Tratamiento , Factores de Riesgo , Factores de Tiempo , Calcinosis/diagnóstico por imagen , Calcinosis/fisiopatología , Calcinosis/mortalidad , Valvuloplastia con Balón/efectos adversos , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/mortalidad , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/fisiopatología , Enfermedades de las Válvulas Cardíacas/cirugía , Enfermedades de las Válvulas Cardíacas/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Trombosis/diagnóstico por imagen , Trombosis/etiología , Tomografía Computarizada Multidetector , Valor Predictivo de las Pruebas
7.
Front Cardiovasc Med ; 11: 1411398, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280032

RESUMEN

The development of drug therapy for the pathological calcification of the aortic valve is still an open issue due to the lack of effective treatment strategies. Currently, the only option for treating this condition is surgical correction and symptom management. The search for models to study the safety and efficacy of anti-calcifying drugs requires them to not only be as close as possible to in vivo conditions, but also to be flexible with regard to the molecular studies that can be applied to them. The ex vivo model has several advantages, including the ability to study the effect of a drug on human cells while preserving the original structure of the valve. This allows for a better understanding of how different cell types interact within the valve, including non-dividing cells. The aim of this study was to develop a reproducible ex vivo calcification model based on valves from patients with calcific aortic stenosis. We aimed to induce spontaneous calcification in valve tissue fragments under osteogenic conditions, and to demonstrate the possibility of significantly suppressing it using a calcification inhibitor. To validate the model, we tested a Notch inhibitor Crenigacestat (LY3039478), which has been previously shown to have an anti-calcifying effect on interstitial cell of the aortic valve. We demonstrate here an approach to testing calcification inhibitors using an ex vivo model of cultured human aortic valve tissue fragments. Thus, we propose that ex vivo models may warrant further investigation for their utility in studying aortic valve disease and performing pre-clinical assessment of drug efficacy.

9.
NIHR Open Res ; 4: 32, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39145099

RESUMEN

Background: Adherence to adjuvant endocrine therapy (AET) is low in women with breast cancer, which increases the risk of recurrence and mortality. A consistently reported barrier to adherence is low perceived necessity of AET and high concerns. Existing interventions to support medication beliefs have mixed effectiveness and rarely target medication beliefs specifically. We developed an information leaflet with five candidate components aiming to increase necessity beliefs about AET and reduce concerns; (1) diagrams explaining how AET works; (2) icon arrays displaying the benefits of AET; (3) information about the prevalence of side-effects; (4) answers to common concerns and (5) quotes and pictures from breast cancer survivors. Guided by the multiphase optimisation strategy (MOST), we aimed to optimise the content of the information leaflet. We planned for the dataset to be open access to provide an exemplar for other investigators to use. Methods: The content of the leaflet was optimised in a fully powered online 2 5 factorial experiment. Each candidate component of the leaflet was operationalised as a factor with two levels; on vs off or enhanced vs basic. Healthy women (n=1604) completed the beliefs about medicines questionnaire and were randomised to view one of 32 versions of the information leaflet. The 32 versions comprised unique combinations of the factor levels corresponding to the five candidate intervention components. Time spent on the information leaflet page of the survey was recorded. After viewing the information leaflet, participants completed the beliefs about medicines questionnaire again, a true/false questionnaire assessing their objective knowledge of AET, a subjective rating of their knowledge of AET, and a questionnaire evaluating their satisfaction with the information they received. Importance of this dataset: The factorial dataset provides the opportunity for other investigators interested in using the MOST framework to learn about complex factorial designs, using a real dataset.


Most women with breast cancer are treated with adjuvant endocrine therapy (AET) to reduce the chance of breast cancer coming back. However, many women do not take the medication as recommended. Women's beliefs about the medication are a common reason for not taking AET. Some women do not think AET will help them, and some women have lots of concerns about AET. At the moment, we do not know the best way to change women's beliefs about AET. Therefore, we ran a study to help us understand what combination of information might help change women's beliefs about AET. We developed a written information leaflet with five parts; (1) diagrams about how AET works; (2) visual figures of the benefits of AET; (3) information about how likely each side-effect is; (4) answers to common concerns about AET; and (5) pictures and quotes from women who have taken AET. In an online survey, 1,604 healthy women answered questions about their beliefs about the medication. Each woman was shown one version of the information leaflet picked at random. There were 32 possible versions of the information leaflet, which contained unique combinations of the five parts of the leaflet. After women read the leaflet, they were asked to complete the same questionnaire about their beliefs about the medication. They were also asked questions about how satisfied they were with the information they received, true or false questions about AET to assess their knowledge after reading the leaflet, and a rating of how informed they felt about AET. We also recorded how long women spent looking at the leaflet. One of our aims was to make the dataset from this experiment openly available so other scientists could use it to learn how to conduct similar experiments.

10.
J Cardiothorac Surg ; 19(1): 501, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198887

RESUMEN

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is indicated for elderly patients who often have severe comorbidities and high operative risk. Despite many advantages, it carries the potential for both early and late complications. The literature reports mainly periprocedural problems. This case report describes a rare instance of ascending aortic rupture as a late complication following TAVI. CASE PRESENTATION: An 81-year-old male with severe aortic stenosis (AS) was a non-surgical patient due to a high operative risk (EuroSCORE II 14.08%) and comorbidities, including cardiovascular problems, chronic obstructive pulmonary disease, myelodysplastic syndrome. During the TAVI procedure Medtronic CoreValve™ Evolut™ R-26 was implanted via the right femoral artery. Postoperative period elapsed without complications and the patient was discharged home. Six months later, the patient was re-admitted to the hospital on an emergency basis and transferred directly to the operating room due to ascending aortic rupture (EuroSCORE II 53.20%, GERAADA score 64.9%). Computed tomography angiography (CTA) showed aortic rupture with a multiple fresh blood reservoirs and thrombus around the ascending aorta originating from the spot where the nitinol frame of the TAVI valve was attached to the native aorta. Supracoronary excision of the ascending aorta with implantation of a vascular graft (Intergard Woven Graft 34 mm) was performed, preserving the earlier implanted TAVI valve. On the 9th day after surgery the patient's general condition deteriorated, he suffered from circulatory and respiratory insufficiency. Furthermore, a gastrointestinal bleeding with the need for gastro-, and colonoscopy and multiple blood transfusions occurred. Patient developed urosepsis and acute renal failure with the need for hemodiafiltration. Despite intensive treatment, further deterioration of the medical condition of the patient. and finally the multiple organ failure was observed. Patient died on the 50th postoperative day. CONCLUSIONS: TAVI is a safe method of treating severe AS, especially recommended for non-surgical candidates. Rupture of the ascending aorta is a rare but serious complication of TAVI that usually occur during or shortly after the procedure. This case report highlights the importance of post-procedural monitoring for such TAVI complications, even in the late period following TAVI, and if such complications occur, taking the risk to perform a life-saving operation.


Asunto(s)
Rotura de la Aorta , Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Anciano de 80 o más Años , Humanos , Masculino , Aorta/diagnóstico por imagen , Aorta/cirugía , Rotura de la Aorta/diagnóstico por imagen , Rotura de la Aorta/etiología , Rotura de la Aorta/cirugía , Estenosis de la Válvula Aórtica/cirugía , Angiografía por Tomografía Computarizada , Prótesis Valvulares Cardíacas/efectos adversos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/instrumentación
11.
Heliyon ; 10(14): e34727, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39130421

RESUMEN

Mitral valve (MV) leaflet elongation is recognized as a primary phenotypic expression of hypertrophic cardiomyopathy (HCM) that contributes to obstruction. This study investigates the correlation between MV length and genotype mutations in the two predominant genes, myosin-binding protein C (MYBPC3), and the ß-myosin heavy chain (MYH7) in patients with obstructive HCM (OHCM). Among the 402 OHCM patients, there were likely pathogenic or pathogenic variations in MYH7 (n = 94) and MYBPC3 (n = 76), along with a mutation-negative group (n = 212). Compared to genotype-negative patients, genotype-positive individuals exhibited elongated MV length, thicker interventricular septum, and increased instances of late gadolinium enhancement. Notably, MYH7 mutations were associated with a more severe disease trajectory than MYBPC3 mutations. After adjusting for potential confounders, multivariate linear regression analysis revealed that MYH7 gene mutations and left ventricular volume were independently associated with MV leaflet elongation. The study indicates that mutations in MYH7 and hemodynamics factors are significant risk factors for elongated MV leaflet. Consequently, regular assessment of MV length, especially in patients with MYH7 mutation and enlarged LV volume, is crucial for timely preoperative strategic planning and improved prognosis.

12.
JACC Basic Transl Sci ; 9(7): 845-864, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39170957

RESUMEN

Pathological tissues release a variety of factors, including extracellular vesicles (EVs) shed by activated or apoptotic cells. EVs trapped within the native pathological valves may act as key mediators of valve thrombosis. Human aortic stenosis EVs promote activation of valvular endothelial cells, leading to endothelial dysfunction, and proadhesive and procoagulant responses.

13.
J Am Coll Cardiol ; 84(9): 848-861, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39168571

RESUMEN

Transcatheter aortic valve (TAV) thrombosis may manifest as subclinical leaflet thrombosis (SLT) and clinical valve thrombosis. SLT is relatively common (10%-20%) after transcatheter aortic valve replacement, but clinical implications are uncertain. Clinical valve thrombosis is rare (1.2%) and associated with bioprosthetic valve failure, neurologic or thromboembolic events, heart failure, and death. Treatment for TAV thrombosis has been understudied. In principle, anticoagulation may prevent TAV thrombosis. Non-vitamin K oral anticoagulants, as compared to antiplatelet therapy, are associated with reduced incidence of SLT, although at the cost of higher bleeding and all-cause mortality risk. We present an overview of existing literature for management of TAV thrombosis and propose a rational treatment algorithm. Vitamin K antagonists or non-vitamin K oral anticoagulants are the cornerstone of antithrombotic treatment. In therapy-resistant or clinically unstable patients, ultraslow, low-dose infusion of thrombolytics seems effective and safe and may be preferred over redo-transcatheter aortic valve replacement or explant surgery.


Asunto(s)
Trombosis , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Trombosis/prevención & control , Trombosis/etiología , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Fibrinolíticos/uso terapéutico , Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas/efectos adversos
14.
J Cardiothorac Surg ; 19(1): 472, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080647

RESUMEN

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has increased in utilization since its approval for management of aortic stenosis patients across all risk strata. We report a rare case of aortic valve leaflet avulsion after balloon expandable TAVR managed with urgent surgery. CASE PRESENTATION: A 78-year-old male underwent TAVR complicated by avulsion of the native aortic valve leaflet's left coronary cusp. He was taken for urgent surgery for cusp resection to prevent thromboembolic complications. CONCLUSIONS: Native aortic valve leaflet avulsion should be suspected during TAVR in instances of extreme hemodynamic instability after balloon aortic valvuloplasty. As TAVR expands in lower risk patients, surgeons should have a low threshold to intervene surgically to treat native leaflet avulsion or other complications.


Asunto(s)
Estenosis de la Válvula Aórtica , Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Masculino , Anciano , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Válvula Aórtica/lesiones
15.
J Clin Med ; 13(14)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39064216

RESUMEN

Background: The mismatch between tricuspid valve (TV) leaflet length and annulus dilation, assessed with the septal-lateral leaflet-to-annulus index (SL-LAI), predicts residual tricuspid regurgitation (TR) following tricuspid transcatheter edge-to-edge-repair (T-TEER). When posterior leaflet grasping is required, the anterior-posterior leaflet-to-annulus index (AP-LAI) may offer additional information. Methods: This single-center retrospective cohort study included all patients referred for T-TEER with severe and symptomatic TR with high surgical risk from April 2021 to March 2024. Patients were categorized into 'optimal result' (

16.
Sci Rep ; 14(1): 16872, 2024 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043900

RESUMEN

Sphingomyelin (SM) is a major sphingolipid in mammalian cells. SM is enriched in the extracellular leaflet of the plasma membrane (PM). Besides this localization, recent electron microscopic and biochemical studies suggest the presence of SM in the cytosolic leaflet of the PM. In the present study, we generated a non-toxic SM-binding variant (NT-EqtII) based on equinatoxin-II (EqtII) from the sea anemone Actinia equina, and examined the dynamics of SM in the cytosolic leaflet of living cell PMs. NT-EqtII with two point mutations (Leu26Ala and Pro81Ala) had essentially the same specificity and affinity to SM as wild-type EqtII. NT-EqtII expressed in the cytosol was recruited to the PM in various cell lines. Super-resolution microscopic observation revealed that NT-EqtII formed tiny domains that were significantly colocalized with cholesterol and N-terminal Lyn. Meanwhile, single molecule observation at high resolutions down to 1 ms revealed that all the examined lipid probes including NT-EqtII underwent apparent fast simple Brownian diffusion, exhibiting that SM and other lipids in the cytosolic leaflet rapidly moved in and out of domains. Thus, the novel SM-binding probe demonstrated the presence of the raft-like domain in the cytosolic leaflet of living cell PMs.


Asunto(s)
Membrana Celular , Venenos de Cnidarios , Citosol , Esfingomielinas , Esfingomielinas/metabolismo , Membrana Celular/metabolismo , Citosol/metabolismo , Animales , Venenos de Cnidarios/metabolismo , Venenos de Cnidarios/genética , Humanos , Anémonas de Mar/metabolismo , Anémonas de Mar/genética , Colesterol/metabolismo
17.
Clin Infect Dis ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997115

RESUMEN

BACKGROUND: Diagnosing infective endocarditis (IE) poses a significant challenge. This study aimed to compare the diagnostic accuracy of the 2015 and 2023 Duke clinical criteria introduced by the European Society of Cardiology (ESC) in a cohort of patients suspected of having IE. METHODS: Conducted retrospectively at two Swiss University Hospitals between 2014-2023, the study involved patients with suspected IE. Each hospitals' Endocarditis Team categorized case as either IE or not IE. The performance of each iteration of the Duke-ESC clinical criteria was assessed based on the agreement between definite IE and the diagnoses made by the Endocarditis Team. RESULTS: Among the 3127 episodes with suspected IE, 1177 (38%) were confirmed to have IE. Using the 2015 Duke-ESC clinical criteria, 707 (23%) episodes were deemed definite IE, with 696 (98%) receiving a final IE diagnosis. With the 2023 Duke-ESC clinical criteria, 855 (27%) episodes were classified as definite IE, of which 813 (95%) were confirmed as IE. The 2015 and 2023 Duke-ESC clinical criteria categorized 1039 (33%) and 1034 (33%) episodes, respectively, as possible IE. Sensitivity for the 2015 Duke-ESC and the 2023 Duke-ESC clinical criteria was calculated at 59% (95% CI: 56-62%), and 69% (66-72%), respectively, with specificity at 99% (99-100%), and 98% (97-98%), respectively. CONCLUSIONS: The 2023 ESC criteria demonstrated significant improvements in sensitivity compared to the 2015 version, although one-third of episodes were classified as possible IE by both versions.

18.
Int J Cardiol ; 413: 132387, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39047796

RESUMEN

BACKGROUND: Various mitral valve (MV) repair techniques are nowadays in use. Non-resection techniques, that rely exclusively on Gore-Tex® neochords and annuloplasty, have been popularized; however, their efficacy in Barlow's disease, characterized by large myxomatous leaflets, is yet unclear. METHODS: Consecutive patients undergoing MV repair for Barlow's disease between 2011 and 2019 were selected on the basis of being eligible for resection and non-resection techniques. Study endpoints included overall survival, freedom from MV reintervention and recurrent regurgitation. RESULTS: Of 209 patients meeting the inclusion criteria, 135 (65%) underwent MV repair with and 74 (35%) without resection. There was one early reoperation due to residual regurgitation (resection group). Mean clinical follow-up duration was 6.1 (IQR 3.9-8.5) years. At 6 years after surgery, there was no difference in overall survival or freedom from MV reintervention. Mean echocardiographic follow-up (95% complete) duration was 3.5 (IQR 2.3-5.8) years. At 6 years, there was no difference in freedom from recurrent regurgitation rate (86.1%, 95% CI 78.5-93.7% vs. 83.0%, 95% CI 71.6-94.4%, P = 0.20) between the groups. Inverse probability-of-treatment weighting adjusted analysis demonstrated no significant difference between groups (HR 0.535, 95% CI 0.212-1.349, P = 0.20). Uni- and multivariable Cox proportional regression analysis did not demonstrate an effect of valve repair technique on the occurrence of recurrent regurgitation. CONCLUSIONS: At mid-term, the clinical and echocardiographic results of valve repair for Barlow's disease were very good and MV reintervention was rarely needed. At this time point, the results of non-resection techniques were comparable to the "gold standard" resection techniques.


Asunto(s)
Válvula Mitral , Humanos , Masculino , Femenino , Persona de Mediana Edad , Válvula Mitral/cirugía , Válvula Mitral/diagnóstico por imagen , Estudios de Seguimiento , Anuloplastia de la Válvula Mitral/métodos , Estudios Retrospectivos , Prolapso de la Válvula Mitral/cirugía , Prolapso de la Válvula Mitral/diagnóstico por imagen , Anciano , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Resultado del Tratamiento , Adulto , Implantación de Prótesis de Válvulas Cardíacas/métodos
19.
Methods Enzymol ; 700: 127-159, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38971598

RESUMEN

The natural asymmetry of the lipid bilayer in biological membranes is, in part, a testament to the complexity of the structure and function of this barrier limiting and protecting cells (or organelles). These lipid bilayers consist of two lipid leaflets with different lipid compositions, resulting in unique interactions within each leaflet. These interactions, combined with interactions between the two leaflets, determine the overall behavior of the membrane. Model membranes provide the most suitable option for investigating the fundamental interactions of lipids. This report describes a comprehensive method to make asymmetric giant unilamellar vesicles (aGUVs) using the technique of hemifusion. In this method, calcium ions induce the hemifusion of giant unilamellar vesicles (GUVs) with a supported lipid bilayer (SLB), both having different lipid compositions. During hemifusion, a stalk, or a more commonly seen hemifusion diaphragm, connects the outer leaflets of GUVs and the SLB. The lateral diffusion of lipids naturally promotes the lipid exchange between the connected outer leaflets. After calcium chelation to prevent further fusion, a mechanical shear detaches aGUVs from the SLB. A fluorescence quench assay is employed to test the extent of bilayer asymmetry. A fluorescence quenching assay tests bilayer asymmetry and verifies dye and lipid migration to a GUV's outer leaflet.


Asunto(s)
Calcio , Membrana Dobles de Lípidos , Liposomas Unilamelares , Liposomas Unilamelares/química , Membrana Dobles de Lípidos/química , Calcio/química , Calcio/metabolismo , Fusión de Membrana
20.
Methods Enzymol ; 700: 349-383, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38971607

RESUMEN

Small-angle X-ray and neutron scattering (SAXS/SANS) techniques excel in unveiling intricate details of the internal structure of lipid membranes under physiologically relevant temperature and buffer conditions, all without the need to resort to bulky labels. By concurrently conducting and analyzing neutron and X-ray data, these methods harness the complete spectrum of contrast and resolution from various components constituting lipid membranes. Despite this, the literature exhibits only a sparse presence of applications compared to other techniques in membrane biophysics. This chapter serves as a primer for conducting joint SAXS/SANS analyses on symmetric and asymmetric large unilamellar vesicles, elucidating fundamental elements of the analysis process. Specifically, we introduce the basics of interactions of X-rays and neutrons with matter that lead to the scattering contrast and a description of membrane structure in terms of scattering length density profiles. These profiles allow fitting of the experimentally observed scattering intensity. We further integrate practical insights, unveiling strategies for successful data acquisition and providing a comprehensive assessment of the technique's advantages and drawbacks. By amalgamating theoretical underpinnings with practical considerations, this chapter aims to dismantle barriers hindering the adoption of joint SAXS/SANS approaches, thereby encouraging an influx of studies in this domain.


Asunto(s)
Difracción de Neutrones , Dispersión del Ángulo Pequeño , Difracción de Rayos X , Difracción de Neutrones/métodos , Difracción de Rayos X/métodos , Lípidos de la Membrana/química , Liposomas Unilamelares/química , Membrana Dobles de Lípidos/química
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