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2.
Artículo en Inglés | MEDLINE | ID: mdl-39283297

RESUMEN

Thoracic endovascular aortic repair is commonly used in the surgical treatment of patients with aortic coarctation, but complications such as endoleaks can occur. This video tutorial presents a case study involving the exclusion of a stent graft from the bloodstream through total transection of the aortic arch and abdominal aorta, with off-pump aortic grafting and debranching of the left carotid and subclavian arteries.


Asunto(s)
Implantación de Prótesis Vascular , Endofuga , Procedimientos Endovasculares , Humanos , Endofuga/etiología , Endofuga/cirugía , Endofuga/diagnóstico , Procedimientos Endovasculares/métodos , Procedimientos Endovasculares/efectos adversos , Implantación de Prótesis Vascular/métodos , Implantación de Prótesis Vascular/efectos adversos , Masculino , Aorta Abdominal/cirugía , Stents , Aorta Torácica/cirugía , Prótesis Vascular/efectos adversos , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico
6.
BMC Surg ; 24(1): 259, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39261808

RESUMEN

BACKGROUND: Techniques in endovascular therapy have evolved to offer a promising alternative to medical therapy alone for Type B aortic dissections (TBADs). AIM: The aim of this meta-analysis was to compare mortality and overall complications between thoracic endovascular aortic repair (TEVAR) and best medical therapy (BMT) in patients with TBADs. METHODS: We included randomized control trials and prospective or retrospective cohort studies that compared TEVAR and BMT for the treatment of type B aortic dissection. Multiple electronic databases were searched. RESULTS: Thirty-two cohort studies including 150,836 patients were included. TEVAR was associated with a significantly lower 30-day mortality rate than BMT (RR = 0.79, CI = 0.63, 0.99, P = 0.04), notably in patients ≥ 65 years of age (RR = 0.78, CI = 0.64, 0.95, P = 0.01). The TEVAR group had a significantly prolonged hospital stay (MD = 3.42, CI = 1.69, 5.13, P = 0.0001) and ICU stay (MD = 3.18, CI = 1.48, 4.89, P = 0.0003) compared to the BMT. BMT was associated with increased stroke risk (RR = 1.52, CI = 1.29, 1.79, P < 0.00001). No statistically significant differences in late mortality (1, 3, and 5 years) or intervention-related factors (acute renal failure, spinal cord ischemia, myocardial infarction, respiratory failure, and sepsis) were noted between the groups. CONCLUSION: Our meta-analysis revealed a significant association between the TEVAR group and a decreased mortality rate of TBAD compared to the medical treatment group, especially in patients aged 65 years or older. Further randomized controlled trials are needed to confirm our findings.


Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Procedimientos Endovasculares , Humanos , Procedimientos Endovasculares/métodos , Disección Aórtica/cirugía , Disección Aórtica/mortalidad , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Anciano , Aorta Torácica/cirugía , Reparación Endovascular de Aneurismas
7.
J Am Heart Assoc ; 13(18): e034496, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39248260

RESUMEN

BACKGROUND: Postoperative computed tomography imaging surveillance is an essential component of care after acute type A aortic dissection (ATAAD) repair. Prognostic imaging factors after ATAAD repair have not been systematically reviewed. METHODS AND RESULTS: We performed a systematic review to summarize postoperative computed tomography measurements including aortic diameter, cross-sectional area, volume, growth rate, and false lumen thrombosis in addition mid- to long-term clinical outcomes after ATAAD repair. Searches were conducted in Medline, Embase, and CENTRAL in October 2022. Studies were included if they reported clinical outcomes such as mortality or aortic reintervention after 1 year and included aforementioned computed tomography findings. Studies of chronic aortic dissection and studies of exclusive patient populations such as those with connective tissue diseases were excluded. Risk of bias was assessed with the Newcastle-Ottawa Scale. Searches retrieved 6999 articles. Sixty-eight studies met inclusion criteria (7885 patients). Extended repairs were associated with improved false lumen thrombosis, decreased aortic growth rate, and decreased rates of reintervention but not improved survival. Growth rates of the aorta post-ATAAD repair were highest in the descending thoracic aorta. The most frequent prognostic imaging factors reported were a patent/partially thrombosed false lumen and postoperative aortic diameter >40 to 45 mm. CONCLUSIONS: Established measurements of positive aortic remodeling, including complete false lumen thrombosis and stabilization of postoperative aortic diameter and growth are the most studied prognostic indicators for improved clinical outcomes after ATAAD repair. Growth rate of the aorta remains significant after ATAAD repair. Future studies should prospectively evaluate and compare prognostic factors for improved surveillance and management.


Asunto(s)
Disección Aórtica , Humanos , Disección Aórtica/cirugía , Disección Aórtica/diagnóstico por imagen , Enfermedad Aguda , Resultado del Tratamiento , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Angiografía por Tomografía Computarizada , Pronóstico , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Aneurisma de la Aorta/cirugía , Aneurisma de la Aorta/diagnóstico por imagen
8.
Rev Neurol ; 79(6): 175-178, 2024 Sep 16.
Artículo en Español, Inglés | MEDLINE | ID: mdl-39267403

RESUMEN

INTRODUCTION: Aortic arch complex atheromatosis is a source of cerebral embolism. A percentage of lacunar infarct could be of embolic etiology, especially due to microemboli of the aortic arch. CASE REPORT: We present the case of a 63-year-old hypertensive man suffering from dysarthria-clumsy hand syndrome for a right hemispheric minor ischemic stroke. The patient developed sequential acute thromboembolism of the left lower and right upper limbs. Computed tomography angiography revealed an aortic arch thrombus. Vascular surgery was successfully performed. CONCLUSION: This case highlights the importance of considering embolic sources in lacunar syndromes, especially at the level of the aortic arch.


TITLE: Síndrome de disartria-mano torpe y embolias agudas secuenciales múltiples de las extremidades como forma de presentación de un trombo del cayado aórtico.Introducción. La ateromatosis del complejo del arco aórtico es una fuente de embolia cerebral. Un porcentaje de infartos lacunares podría ser de etiología embólica, especialmente debidos a microembolias del arco aórtico. Caso clínico. Presentamos el caso de un varón hipertenso de 63 años con síndrome de disartria-mano torpe por un ictus isquémico minor hemisférico derecho. El paciente desarrolló un tromboembolismo agudo secuencial de los miembros inferior izquierdo y superior derecho. La angiografía por tomografía computarizada reveló un trombo en el arco aórtico. La cirugía vascular se llevó a cabo con éxito. Conclusión. Este caso destaca la importancia de considerar las fuentes embólicas en los síndromes lacunares, especialmente en el arco aórtico.


Asunto(s)
Aorta Torácica , Disartria , Humanos , Masculino , Persona de Mediana Edad , Disartria/etiología , Aorta Torácica/diagnóstico por imagen , Mano/irrigación sanguínea , Síndrome , Enfermedad Aguda , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/complicaciones
9.
J Cardiothorac Surg ; 19(1): 528, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39272203

RESUMEN

BACKGROUND: It is challenging to simultaneously conduct total endovascular repair and reconstruct the left subclavian artery (LSA) and isolated left vertebral artery (ILVA) in patients who had an ILVA and required zone 2 anchoring. This pilot study reported the initial application experience of thoracic endovascular aortic repair (TEVAR) with a proximal zone 2 landing for aortic arch reconstruction in patients with ILVA. METHODS: This study was a retrospective consecutive single-center case series analysis, which involved four patients with ILVA who required zone 2 anchoring and received TEVAR combined with a single-branched stent graft and concomitant on-table fenestration between March 2021 and December 2022. RESULTS: The postoperative follow-up period was 6-27 months, and no postoperative deaths or other primary complications occurred. There were no signs of a stroke or spinal cord ischemia, as well as no chest or back pain. The postoperative computed tomography angiography showed unobstructed ILVA and LSA, no stent stenosis and displacement, and no signs of endoleak. CONCLUSION: The outcome suggested that this technique might be a feasible, safe, and alternative treatment for such patients. Further studies with larger samples and longer follow-up periods are needed to confirm our findings.


Asunto(s)
Aorta Torácica , Procedimientos Endovasculares , Stents , Arteria Vertebral , Humanos , Proyectos Piloto , Masculino , Procedimientos Endovasculares/métodos , Estudios Retrospectivos , Femenino , Anciano , Persona de Mediana Edad , Aorta Torácica/cirugía , Aorta Torácica/diagnóstico por imagen , Arteria Vertebral/cirugía , Aneurisma de la Aorta Torácica/cirugía , Diseño de Prótesis , Implantación de Prótesis Vascular/métodos , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Arteria Subclavia/cirugía , Angiografía por Tomografía Computarizada , Resultado del Tratamiento , Reparación Endovascular de Aneurismas
10.
J Biomech ; 175: 112266, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39232449

RESUMEN

We introduce a new computational framework that utilises Pulse Wave Velocity (PWV) extracted directly from 4D flow MRI (4DMRI) to inform patient-specific compliant computational fluid dynamics (CFD) simulations of a Type-B aortic dissection (TBAD), post-thoracic endovascular aortic repair (TEVAR). The thoracic aortic geometry, a 3D inlet velocity profile (IVP) and dynamic outlet boundary conditions are derived from 4DMRI and brachial pressure patient data. A moving boundary method (MBM) is applied to simulate aortic wall displacement. The aortic wall stiffness is estimated through two methods: one relying on area-based distensibility and the other utilising regional pulse wave velocity (RPWV) distensibility, further fine-tuned to align with in vivo values. Predicted pressures and outlet flow rates were within 2.3 % of target values. RPWV-based simulations were more accurate in replicating in vivo hemodynamics than the area-based ones. RPWVs were closely predicted in most regions, except the endograft. Systolic flow reversal ratios (SFRR) were accurately captured, while differences above 60 % in in-plane rotational flow (IRF) between the simulations were observed. Significant disparities in predicted wall shear stress (WSS)-based indices were observed between the two approaches, especially the endothelial cell activation potential (ECAP). At the isthmus, the RPWV-driven simulation indicated a mean ECAP>1.4 Pa-1 (critical threshold), indicating areas potentially prone to thrombosis, not captured by the area-based simulation. RPWV-driven simulation results agree well with 4DMRI measurements, validating the proposed pipeline and facilitating a comprehensive assessment of surgical decision-making scenarios and potential complications, such as thrombosis and aortic growth.


Asunto(s)
Modelos Cardiovasculares , Análisis de la Onda del Pulso , Humanos , Análisis de la Onda del Pulso/métodos , Procedimientos Endovasculares/métodos , Disección Aórtica/fisiopatología , Disección Aórtica/cirugía , Simulación por Computador , Aorta Torácica/cirugía , Aorta Torácica/fisiología , Aorta Torácica/fisiopatología , Aorta Torácica/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Velocidad del Flujo Sanguíneo/fisiología , Hemodinámica/fisiología , Reparación Endovascular de Aneurismas
12.
Ren Fail ; 46(2): 2394633, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39230198

RESUMEN

OBJECTIVE: This study aimed to investigate the effect of the soluble Klotho (sKlotho)/Wnt/ß-catenin signaling pathway on vascular calcification in rat models of chronic kidney disease (CKD) and the intervention effect of Shenyuan granules. METHODS: Rats with 5/6 nephrectomy and high phosphorus feeding were used to establish the vascular calcification model. The rats were given gradient doses of Shenyuan granules aqueous solution and calcitriol solution by gavage for 8 weeks, which were divided into experimental group and positive control group. RESULTS: The 5/6 nephrectomy combined with high phosphorus feeding induced thoracic aortic calcification in rats. Shenyuan granules intervention increased the serum sKlotho level, inhibited the mRNA and protein expression of Wnt1, ß-catenin, and Runx2 in the thoracic aorta, and alleviated thoracic aortic media calcification in rats. CONCLUSION: Shenyuan granules may partially regulate the Wnt/ß-catenin signaling pathway via serum sKl to interfere with the expression of Runx2, thereby improving vascular calcification in CKD.


Asunto(s)
Medicamentos Herbarios Chinos , Glucuronidasa , Proteínas Klotho , Insuficiencia Renal Crónica , Calcificación Vascular , Vía de Señalización Wnt , beta Catenina , Animales , Masculino , Ratas , Aorta Torácica/metabolismo , Aorta Torácica/patología , beta Catenina/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Glucuronidasa/metabolismo , Glucuronidasa/genética , Proteínas Klotho/metabolismo , Nefrectomía , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/complicaciones , Calcificación Vascular/metabolismo , Calcificación Vascular/etiología , Calcificación Vascular/patología , Vía de Señalización Wnt/efectos de los fármacos , Proteína Wnt1/metabolismo , Proteína Wnt1/genética
13.
Langenbecks Arch Surg ; 409(1): 274, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251463

RESUMEN

PURPOSE: Anatomical understanding is an important basis for medical teaching, especially in a surgical context. The interpretation of complex vascular structures via two-dimensional visualization can yet be difficult, particularly for students. The objective of this study was to investigate the feasibility of an MxR-assisted educational approach in vascular surgery undergraduate education, comparing an MxR-based teaching-intervention with CT-based material for learning and understanding the vascular morphology of the thoracic aorta. METHODS: In a prospective randomized controlled trial learning success and diagnostic skills following an MxR- vs. a CT-based intervention was investigated in 120 thoracic aortic visualizations. Secondary outcomes were motivation, system-usability as well as workload/satisfaction. Motivational factors and training-experience were also assessed. Twelve students (7 females; mean age: 23 years) were randomized into two groups undergoing educational intervention with MxR or CT. RESULTS: Evaluation of learning success showed a mean improvement of 1.17 points (max.score: 10; 95%CI: 0.36-1.97). The MxR-group has improved by a mean of 1.33 [95% CI: 0.16-2.51], against 1.0 points [95% CI: -0.71- 2.71] in the CT-group. Regarding diagnostic skills, both groups performed equally (CT-group: 58.25 ± 7.86 vs. MxR-group:58.5 ± 6.60; max. score 92.0). 11/12 participants were convinced that MxR facilitated learning of vascular morphologies. The usability of the MxR-system was rated positively, and the perceived workload was low. CONCLUSION: MxR-systems can be a valuable addition to vascular surgery education. Further evaluation of the technology in larger teaching situations are required. Especially regarding the acquisition of practical skills, the use of MxR-systems offers interesting application possibilities in surgical education.


Asunto(s)
Aorta Torácica , Educación de Pregrado en Medicina , Humanos , Femenino , Masculino , Proyectos Piloto , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/anatomía & histología , Estudios Prospectivos , Adulto Joven , Educación de Pregrado en Medicina/métodos , Adulto , Realidad Aumentada , Estudios de Factibilidad , Tomografía Computarizada por Rayos X , Procedimientos Quirúrgicos Vasculares/educación , Competencia Clínica , Anatomía/educación
14.
J Cardiothorac Surg ; 19(1): 519, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251978

RESUMEN

BACKGROUND: Mega-aortic syndrome including aortic arch and descending aortic aneurysm is a challenging surgical case. Because the aorta continuously dilates, creating the distal anastomosis sites becomes an issue. Despite the developments in endovascular techniques including frozen elephant trunk, in the case of mega-aortic syndrome or mycotic aneurysm, extensive surgical repair is still a strong armamentarium. Our patient had a mega-aorta with chronic aortic dissection. Herein, we show tips regarding concurrent ascending, aortic arch, and descending aortic replacement via posterolateral thoracotomy for this relatively young patient. CASE PRESENTATION: A 46-year-old man with chronic kidney disease had chronic type A aortic dissection with an extensively dilated thoracic aorta from the distal ascending to the descending aorta measuring 63 mm in diameter and abdominal aorta measuring 50 mm. The short segment of the distal descending aorta was narrowed to 36 mm. The patient underwent a concurrent replacement of the distal ascending aorta, aortic arch, and descending aorta via a posterolateral thoracotomy. The patient was extubated on postoperative day (POD) 1 and discharged home without serious complications such as stroke, respiratory failure, or renal failure on POD 18. The 1-year follow-up computed tomography did not find issues in the anastomosis sites; however, the abdominal aorta enlarged from 50 to 58 mm. The patient underwent a thoracoabdominal aortic replacement and recovered well without any complications. CONCLUSIONS: Good exposure and meticulous organ protection methods are key to a safe concurrent replacement of the ascending, aortic arch, and descending aorta via posterolateral thoracotomy.


Asunto(s)
Aorta Torácica , Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Toracotomía , Humanos , Masculino , Persona de Mediana Edad , Disección Aórtica/cirugía , Disección Aórtica/complicaciones , Toracotomía/métodos , Aorta Torácica/cirugía , Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Implantación de Prótesis Vascular/métodos , Tomografía Computarizada por Rayos X , Enfermedad Crónica
16.
J Cardiothorac Surg ; 19(1): 514, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39238045

RESUMEN

BACKGROUND: Type A acute aortic dissection (TAAAD) is a deadly condition that demands immediate surgery, because it involves a critically. The mortality and morbidity associated with it are significant, and it is vital that the patient's conditions and treatment strategies are fully understood to ensure the appropriate management of TAAAD. This study aims to ascertain whether hemiarch repair (HAR) versus extended arch repair (EAR) with or without descending aortic intervention results in better perioperative and late outcomes for patients with TAAAD. METHODS: Four leading centers of cardiac surgery from two European countries have joined forces to create a groundbreaking multicenter observational registry (AoArch). This study was approved by the institutional review board (IRB 202201173). We conducted a retrospective review (NCT00591263) of our prospectively maintained database for patients who underwent operative repair of DeBakey type I or type II dissection from January 1, 2005 to March 2024 (NCT05927090). We will analyze how patient co-morbidities, referral conditions, and surgical strategies involving hemi-arch repair (HAR) and extended arch repair (EAR) impact early and late adverse events. We have developed a procedure urgency algorithm based on the severity of preoperative hemodynamic conditions and malperfusion due to TAAAD, and we will use it to assess the primary clinical outcomes: in-hospital mortality, late mortality, and reoperations on the aorta. We will define secondary outcomes as permanent neurologic deficit, the need for new dialysis, respiratory failure, a composite of major adverse events (myocardial infarction, cerebrovascular accidents, the need for dialysis, or the need for tracheostomy), and a composite of major adverse pulmonary events (intubation over 48 h, pneumonia, reintubation, tracheostomy), and reoperation due to bleeding. DISCUSSION: This multicenter registry will definitively determine the prognostic significance of critical preoperative conditions and the efficacy of extended arch interventions and hemiarch repair in reducing the risk of early adverse events after surgery for TAAAD. This registry will provide insights into the long-term durability of different strategies of surgical repair for TAAAD.


Asunto(s)
Aorta Torácica , Aneurisma de la Aorta Torácica , Disección Aórtica , Sistema de Registros , Humanos , Disección Aórtica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Estudios Retrospectivos , Aorta Torácica/cirugía , Mortalidad Hospitalaria , Masculino , Femenino , Complicaciones Posoperatorias/epidemiología , Persona de Mediana Edad
17.
Artículo en Inglés | MEDLINE | ID: mdl-39248719

RESUMEN

Presenting this video tutorial, we want to demonstrate a step-by-step surgical approach to acute intramural haematoma of the thoracic aorta without a definite entry tear. Limited by the aortic valve proximally, the intramural haematoma involved the aortic root, ascending aorta, aortic arch, including adjacent parts of supra-aortic branches, and descending aorta extending to the diaphragmatic level. The operative strategy involved urgent total aortic arch replacement with the frozen elephant trunk technique and anatomical reimplantation of the three supra-aortic vessels. The direct open over-the-wire technique was used to cannulate the right axillary artery, and standard venous cannulation was performed while brain protection was achieved with bilateral selective antegrade cerebral perfusion.


Asunto(s)
Aorta Torácica , Implantación de Prótesis Vascular , Hematoma , Humanos , Aorta Torácica/cirugía , Hematoma/cirugía , Hematoma/etiología , Hematoma/diagnóstico , Implantación de Prótesis Vascular/métodos , Masculino , Prótesis Vascular , Enfermedades de la Aorta/cirugía , Enfermedades de la Aorta/diagnóstico , Femenino , Persona de Mediana Edad , Anciano , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico
18.
Artículo en Inglés | MEDLINE | ID: mdl-39219482

RESUMEN

The definitive management of combined aortic arch and descending aortic pathologies such as aneurysms and dissections is either a single or staged operation associated with high morbidity and mortality. Stroke, kidney dysfunction, coagulopathy and high blood transfusion requirements are all affiliated with hypothermic circulatory arrest and prolonged cardiopulmonary bypass times. Considering the perilous nature of these operations, the authors describe a step-by-step zone 2 arch replacement as a staged frozen elephant trunk procedure, which provides an adequate landing zone for a later-placed endovascular stent yet maintains a short cardiopulmonary bypass time and no circulatory arrest.


Asunto(s)
Aorta Torácica , Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Humanos , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Implantación de Prótesis Vascular/efectos adversos , Disección Aórtica/cirugía , Procedimientos Endovasculares/métodos , Masculino , Stents , Puente Cardiopulmonar/métodos , Prótesis Vascular , Femenino , Persona de Mediana Edad
19.
J R Soc Interface ; 21(217): 20240110, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39192727

RESUMEN

The renin-angiotensin system plays a key role in regulating blood pressure, which has motivated many investigations of associated mouse models of hypertensive arterial remodelling. Such studies typically focus on histological and cell biological changes, not wall mechanics. This study explores tissue-level ramifications of chronic angiotensin II infusion in wild-type (WT) and type 1b angiotensin II (AngII) receptor null (Agtr1b -/-) mice. Biaxial biomechanical and immunohistological changes were quantified and compared in the thoracic and abdominal aorta in these mice following 14 and 28 days of angiotensin II infusion. Preliminary results showed that changes were largely independent of sex. Associated thickening and stiffening of the aortic wall in male mice differed significantly between thoracic and abdominal regions and between genotypes. Notwithstanding multiple biomechanical changes in both WT and Agtr1b -/- mice, AngII infusion caused distinctive wall thickening and inflammation in the descending thoracic aorta of WT, but not Agtr1b -/-, mice. Our study underscores the importance of exploring differential roles of receptor-dependent angiotensin II signalling along the aorta and its influence on distinct cell types involved in regional histomechanical remodelling. Disrupting the AT1b receptor primarily affected inflammatory cell responses and smooth muscle contractility, suggesting potential therapeutic targets.


Asunto(s)
Angiotensina II , Ratones Noqueados , Receptor de Angiotensina Tipo 1 , Remodelación Vascular , Animales , Angiotensina II/farmacología , Angiotensina II/metabolismo , Ratones , Masculino , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 1/genética , Femenino , Aorta Torácica/metabolismo , Aorta Torácica/patología
20.
Vascul Pharmacol ; 156: 107418, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39159736

RESUMEN

Substituted catechols include both natural and synthetic compounds found in the environment and foods. Some of them are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. Our previous findings showed that one of these metabolites, 4-methylcatechol, exerts potent vasorelaxant effects in rats. In the current study, we aimed at testing of its 22 structural congeners in order to find the most potent structure and to investigate the mechanism of action. 3-methoxycatechol (3-MOC), 4-ethylcatechol, 3,5-dichlorocatechol, 4-tert-butylcatechol, 4,5-dichlorocatechol, 3-fluorocatechol, 3-isopropylcatechol, 3-methylcatechol and the parent 4-methylcatechol exhibited high vasodilatory activities on isolated rat aortic rings with EC50s ranging from ∼10 to 24 µM. Some significant sex-differences were found. The most potent compound, 3-MOC, relaxed also resistant mesenteric artery but not porcine coronary artery, and decreased arterial blood pressure in both male and female spontaneously hypertensive rats in vivo without affecting heart rate. It potentiated the vasodilation mediated by cAMP and cGMP, but did not impact L-type Ca2+-channels. By using two inhibitors, activation of voltage-gated potassium channels (KV) was found to be involved in the mechanism of action. This was corroborated by docking analysis of 3-MOC with the KV7.4 channel. None of the most active catechols decreased the viability of the A-10 rat embryonic thoracic aorta smooth muscle cell line. Our findings showed that various catechols can relax vascular smooth muscles and hence could provide templates for developing new antihypertensive vasodilator agents without affecting coronary circulation.


Asunto(s)
Catecoles , Arterias Mesentéricas , Simulación del Acoplamiento Molecular , Ratas Endogámicas SHR , Vasodilatación , Vasodilatadores , Animales , Vasodilatación/efectos de los fármacos , Masculino , Catecoles/farmacología , Catecoles/química , Vasodilatadores/farmacología , Vasodilatadores/química , Femenino , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/metabolismo , Canales de Potasio con Entrada de Voltaje/metabolismo , Canales de Potasio con Entrada de Voltaje/antagonistas & inhibidores , Canales de Potasio con Entrada de Voltaje/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Porcinos , Relación Dosis-Respuesta a Droga , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipertensión/metabolismo , Presión Arterial/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/metabolismo , Ratas , Factores Sexuales , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Modelos Animales de Enfermedad , Relación Estructura-Actividad , GMP Cíclico/metabolismo
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