Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 827
Filtrar
1.
Sci Rep ; 14(1): 1438, 2024 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-38228786

RESUMEN

Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C-C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague-Dawley rats underwent surgical AAA formation using porcine pancreatic elastase and received daily ß-aminopropionitrile to promote AAA rupture. Rats with AAAs received either a standard diet, ketogenic diet (KD), or exogenous KBs (EKB). Rats receiving KD and EKB reached a state of ketosis and had significant reduction in AAA expansion and incidence of rupture. Ketosis also led to significantly reduced aortic CCR2 content, improved MMP balance, and reduced ECM degradation. Consistent with these findings, we also observed that Ccr2-/- mice have significantly reduced AAA expansion and rupture. In summary, this study demonstrates that CCR2 is essential for AAA expansion, and that its modulation with ketosis can reduce AAA pathology. This provides an impetus for future clinical studies that will evaluate the impact of ketosis on human AAA disease.


Asunto(s)
Aneurisma de la Aorta Abdominal , Rotura de la Aorta , Cetosis , Animales , Humanos , Masculino , Ratones , Ratas , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/metabolismo , Rotura de la Aorta/patología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Matriz Extracelular/metabolismo , Inflamación/patología , Cetosis/patología , Ratas Sprague-Dawley , Porcinos
2.
Int J Legal Med ; 138(1): 301-306, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36773089

RESUMEN

All unexpected deaths of children require an autopsy to determine the cause of death. In cases of aortic rupture, the immediate cause of death is easily identified at autopsy. Although the majority of aortic ruptures are caused by high-energy trauma, other causes should not be missed.We present and discuss the case of a 29-month-old child who died suddenly at home. Her recent medical history and the ecchymotic lesions observed on external examination of the body appeared potentially suspicious of physical abuse. The autopsy concluded that death was due to complete rupture of the abdominal aorta with associated vertebral disjunction. At first glance, the overall forensic picture could suggest a traumatic death. However, careful inspection of the retroperitoneum revealed a discrete atypical mass of infiltrative tissue within the hematoma. Histopathological examinations confirmed tumor proliferation of the soft tissues, triggering vascular and spinal injuries. Other paraneoplastic elements or metastases were ultimately revealed (orbital and subcutaneous). Overall, this was a rare and fatal case of abdominal aortic rupture induced by tumors. Due to the mechanisms and the forces needed to cause vertebral dislocations and aortic rupture, the combination of the two is highly suggestive of child abuse when an accidental traumatic history is absent or inconsistent with the injuries. Nevertheless, this case illustrates the importance of a systematic and rigorous forensic examination, rather than ignoring other possible diagnoses.


Asunto(s)
Rotura de la Aorta , Maltrato a los Niños , Humanos , Niño , Femenino , Preescolar , Rotura de la Aorta/patología , Muerte Súbita/etiología , Muerte Súbita/patología , Maltrato a los Niños/diagnóstico , Autopsia
3.
Rozhl Chir ; 101(8): 401-409, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36208936

RESUMEN

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a relatively frequent and serious condition in vascular surgery. The diagnostic and indication process and its treatment are driven by the guidelines which dictate an intervention when the maximum AAA diameter is more than 55 mm. Nevertheless, this approach is not fully sufficient in all AAA cases and thus we have been seeking to develop a modern diagnostic tool using computer modeling and vascular wall stress analysis. METHODS: The project has been ongoing in cooperation with engineers from VUT Brno (Brno University of Technology) and VŠB Ostrava (Technical University of Ostrava) for ten years. The design of the analytical tool was created during the first, experimental period of the project; this tool is able to assess vascular wall stress from regular CT scans using the finite element method. This primary model was gradually altered and its precision was increased considerably in the course of the years using data from mechanical and histological tests of AAA wall specimens harvested during open repairs. Additionally, other patient specific data are included in the analysis such as blood pressure, gender and material characteristics. RESULTS: The effectiveness of the method was evaluated in a pseudo-prospective study, showing clear superiority of the vascular wall stress analysis over the maximum diameter approach. The method was used in clinical practice for the first time during restrictions due to the COVID-19 pandemic; based on the analysis we were able to assess which AAA cases can be postponed and which had a high risk of rupture and an intervention was required despite the restrictions. The method achieved 100% sensitivity, and its specificity was also much better compared to the maximum diameter approach. CONCLUSION: The vascular wall stress analysis of AAA seems to be much more precise than the classic indication approach based only on the maximum diameter, and it can be used to determine the therapy based on patient specific parameters.


Asunto(s)
Aneurisma de la Aorta Abdominal , Rotura de la Aorta , COVID-19 , Aorta Abdominal , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Rotura de la Aorta/patología , Prueba de COVID-19 , Humanos , Pandemias , Estudios Prospectivos , Estrés Mecánico
4.
J Thorac Cardiovasc Surg ; 163(3): e215-e226, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34586071

RESUMEN

OBJECTIVE: Aortic aneurysm and dissection are major life-threatening complications of Marfan syndrome. Avoiding factors that promote aortic damage is critical in managing the care of these patients. Findings from clinical and animal studies raise concerns regarding fluoroquinolone use in patients at risk for aortic aneurysm and dissection. Therefore, we examined the effects of ciprofloxacin on aortic aneurysm and dissection development in Marfan mice. METHODS: Eight-week-old Marfan mice (Fbn1C1041G/+) were given ciprofloxacin (100 mg/kg/d; n = 51) or vehicle (n = 59) for 4 weeks. Mice were monitored for 16 weeks. Aortic diameters were measured by using ultrasonography, and aortic structure was examined by using histopathologic and immunostaining analyses. RESULTS: Vehicle-treated Fbn1C1041G/+ mice showed progressive aortic enlargement, with aortic rupture occurring in 5% of these mice. Compared with vehicle-treated Fbn1C1041G/+ mice, ciprofloxacin-treated Fbn1C1041G/+ mice showed accelerated aortic enlargement (P = .01) and increased incidences of aortic dissection (25% vs 47%, P = .03) and rupture (5% vs 25%, P = .005). Furthermore, ciprofloxacin-treated Fbn1C1041G/+ mice had higher levels of elastic fiber fragmentation, matrix metalloproteinase expression, and apoptosis than did vehicle-treated Fbn1C1041G/+ mice. CONCLUSIONS: Ciprofloxacin accelerates aortic root enlargement and increases the incidence of aortic dissection and rupture in Marfan mice, partially by suppressing lysyl oxidase expression and further compromising the inherited defect in aortic elastic fibers. Our findings substantiate that ciprofloxacin should be avoided in patients with Marfan syndrome.


Asunto(s)
Antibacterianos/toxicidad , Aorta/efectos de los fármacos , Aneurisma de la Aorta/inducido químicamente , Disección Aórtica/inducido químicamente , Rotura de la Aorta/inducido químicamente , Ciprofloxacina/toxicidad , Fibrilina-1/genética , Remodelación Vascular/efectos de los fármacos , Disección Aórtica/genética , Disección Aórtica/metabolismo , Disección Aórtica/patología , Animales , Aorta/metabolismo , Aorta/ultraestructura , Aneurisma de la Aorta/genética , Aneurisma de la Aorta/metabolismo , Aneurisma de la Aorta/patología , Rotura de la Aorta/genética , Rotura de la Aorta/metabolismo , Rotura de la Aorta/patología , Apoptosis/efectos de los fármacos , Dilatación Patológica , Progresión de la Enfermedad , Tejido Elástico/efectos de los fármacos , Tejido Elástico/metabolismo , Tejido Elástico/ultraestructura , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Masculino , Metaloproteinasas de la Matriz/metabolismo , Ratones Noqueados , Fenotipo , Proteína-Lisina 6-Oxidasa/metabolismo
5.
J Vasc Res ; 59(1): 34-42, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34758464

RESUMEN

Accurately assessing the complex tissue mechanics of cerebral aneurysms (CAs) is critical for elucidating how CAs grow and whether that growth will lead to rupture. The factors that have been implicated in CA progression - blood flow dynamics, immune infiltration, and extracellular matrix remodeling - all occur heterogeneously throughout the CA. Thus, it stands to reason that the mechanical properties of CAs are also spatially heterogeneous. Here, we present a new method for characterizing the mechanical heterogeneity of human CAs using generalized anisotropic inverse mechanics, which uses biaxial stretching experiments and inverse analyses to determine the local Kelvin moduli and principal alignments within the tissue. Using this approach, we find that there is significant mechanical heterogeneity within a single acquired human CA. These results were confirmed using second harmonic generation imaging of the CA's fiber architecture and a correlation was observed. This approach provides a single-step method for determining the complex heterogeneous mechanics of CAs, which has important implications for future identification of metrics that can improve accuracy in prediction risk of rupture.


Asunto(s)
Arterias Cerebrales/patología , Matriz Extracelular/patología , Aneurisma Intracraneal/patología , Modelos Cardiovasculares , Rotura de la Aorta/patología , Rotura de la Aorta/fisiopatología , Fenómenos Biomecánicos , Angiografía Cerebral , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/fisiopatología , Circulación Cerebrovascular , Angiografía por Tomografía Computarizada , Dilatación Patológica , Colágenos Fibrilares , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/fisiopatología , Angiografía por Resonancia Magnética , Estrés Mecánico
7.
Ann Vasc Surg ; 77: 263-273, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34411677

RESUMEN

BACKGROUND: The thoracic aorta is a site of multiple pathological processes, such as aneurysms and dissections. When considering the development of endovascular devices, this vessel has been extensively manipulated because of aortic diseases, as well as to serve as a route for procedures involving the head and neck vessels. Therefore, the aim of the present study was to obtain biomechanical experimental information about the strength and deformability of this vessel. MATERIALS AND METHODS: Thirty-one thoracic aorta specimens were harvested during the autopsy procedure. They were carefully dissected and transversally sectioned according to Criado's aortic arch map landing zones (0 to 4). The supra-aortic trunks were removed, and the aortic rings were opened in their convexity, which resulted in flat tissue segments. Four millimeter-wide strips were prepared from each zone after which they were attached to a clip system connected to the INSTRON SPEC 2200 device, which was responsible for pulling the fragment up to its rupture during the uniaxial tension test. The INSPEC software was used to coordinate the test, and data management was conducted via the SERIES IX software. The biomechanical variables that were measured included failure stress, failure tension, and failure strain. RESULTS: When comparing the five segments from all 31 aortas, three different strength levels were observed. Zones 0 and 1 exhibited the highest failure stress and failure tension values, followed by Zones 2 and 4. Zone 3 (aortic isthmus) was the weakest segment that was tested when compared to the stress and tension of Zones 0 and 1 (P < 0.001), the stress and tension of Zone 2 (P = 0.005 and P = 0.002, respectively) and the stress and tension of Zone 4 (P = 0.023 and P = 0.006, respectively). Among donors > 65 years-old, women presented significantly weaker descending aortas than men in regards to stress (P = 0.049) and tension (P = 0.014). Among male donors, the elderly donors presented significantly stiffer aortic walls and weaker ascending (P = 0.029 for stress) and descending (P = 0.004 for stress; P = 0.031 for tension) aortas than younger men. CONCLUSIONS: Uniaxial tensile strength tests revealed that the thoracic aorta is a very heterogeneous vessel. Isthmus frailty may add to the understanding of the pathophysiology of some aortic diseases that commonly compromise this region. The lower strength that was verifiedin some aortic segments from elderly donors may contribute to the genesis of some thoracic aorta diseases among that group of donors. These data can contribute to the development of new endovascular devices that are specifically designed for this vessel.


Asunto(s)
Aorta Torácica/fisiopatología , Rotura de la Aorta/fisiopatología , Factores de Edad , Anciano , Anciano de 80 o más Años , Aorta Torácica/patología , Rotura de la Aorta/patología , Fenómenos Biomecánicos , Cadáver , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Resistencia a la Tracción
8.
Sci Rep ; 11(1): 13826, 2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-34226632

RESUMEN

Rupture risk stratification is critical for incidentally detected intracranial aneurysms. Here we developed and validated an institutional nomogram to solve this issue. We reviewed the imaging and clinical databases for aneurysms from January 2015 to September 2018. Aneurysms were reconstructed and morphological features were extracted by the Pyradiomics in python. Multiple logistic regression was performed to develop the nomogram. The consistency of the nomogram predicted rupture risks and PHASES scores was assessed. The performance of the nomogram was evaluated by the discrimination, calibration, and decision curve analysis (DCA). 719 aneurysms were enrolled in this study. For each aneurysm, twelve morphological and nine clinical features were obtained. After logistic regression, seven features were enrolled in the nomogram, which were SurfaceVolumeRatio, Flatness, Age, Hyperlipemia, Smoker, Multiple aneurysms, and Location of the aneurysm. The nomogram had a positive and close correlation with PHASES score in predicting aneurysm rupture risks. AUCs of the nomogram in discriminating aneurysm rupture status was 0.837 in a separate testing set. The calibration curves fitted well and DCA demonstrated positive net benefits of the nomogram in guiding clinical decisions. In conclusion, Pyradiomics derived morphological features based institutional nomogram was useful for aneurysm rupture risk stratification.


Asunto(s)
Aneurisma/diagnóstico , Rotura de la Aorta/diagnóstico , Medición de Riesgo , Accidente Cerebrovascular/diagnóstico , Anciano , Aneurisma/diagnóstico por imagen , Aneurisma/epidemiología , Aneurisma/patología , Rotura de la Aorta/diagnóstico por imagen , Rotura de la Aorta/epidemiología , Rotura de la Aorta/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nomogramas , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/patología
9.
PLoS One ; 16(7): e0255238, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34310653

RESUMEN

INTRODUCTION: Aortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model. METHODS: LUM expression patterns were analyzed using aortic tissues of AD patients, and serum soluble LUM (s-LUM) levels were compared between patients with acute AD (AAD) and chronic AD (CAD). Lum-knockout (Lum-/-) mice were challenged with ß-aminopropionitrile (BAPN) and angiotensin II (Ang II) to induce AD. The survival rate, AD incidence, and aortic aneurysm (AA) in these mice were compared with those in BAPN-Ang II-challenged wildtype (WT) mice. Tgf-ß/Smad2, Mmps, Lum, and Nox expression patterns were examined. RESULTS: LUM expression was detected in the intima and media of the ascending aorta in patients with AAD. Serum s-LUM levels were significantly higher in patients with AAD than CAD. Furthermore, AD-associated mortality and thoracic aortic rupture incidence were significantly higher in the Lum-/- AD mice than in the WT AD mice. However, no significant pathologic changes in AA were observed in the Lum-/- AD mice compared with the WT AD mice. The BAPN-Ang II-challenged WT and Lum-/- AD mice had higher Tgf-ß, p-Smad2, Mmp2, Mmp9, and Nox4 levels than those of non-AD mice. We also found that Lum expression was significantly higher in the BAPN-Ang II-challenged WT in comparison to the unchallenged WT mice. CONCLUSION: LUM expression was altered in patients with AD display increased s-LUM in blood, and Lum-/- mice exhibited augmented AD pathogenesis. These findings support the notion that LUM is a biomarker signifying the pathogenesis of injured aorta seen in AAD. The presence of LUM is essential for maintenance of connective tissue integrity. Future studies should elucidate the mechanisms underlying LUM association in aortic changes.


Asunto(s)
Disección Aórtica/patología , Lumican/sangre , Enfermedad Aguda , Aminopropionitrilo/farmacología , Disección Aórtica/metabolismo , Disección Aórtica/mortalidad , Angiotensina II/farmacología , Animales , Aorta/metabolismo , Aorta/patología , Rotura de la Aorta/epidemiología , Rotura de la Aorta/patología , Biomarcadores/sangre , Enfermedad Crónica , Modelos Animales de Enfermedad , Humanos , Incidencia , Estimación de Kaplan-Meier , Lumican/deficiencia , Lumican/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína Smad2/genética , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia Arriba/efectos de los fármacos
10.
Cell Rep Med ; 2(5): 100261, 2021 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-34095874

RESUMEN

Aortic rupture and dissection are life-threatening complications of ascending thoracic aortic aneurysms (aTAAs), and risk assessment has been largely based on the monitoring of lumen size enlargement. Temporal changes in the extracellular matrix (ECM), which has a critical impact on aortic remodeling, are not routinely evaluated, and cardiovascular biomarkers do not exist to predict aTAA formation. Here, Raman microspectroscopy and Raman imaging are used to identify spectral biomarkers specific for aTAAs in mice and humans by multivariate data analysis (MVA). Multivariate curve resolution-alternating least-squares (MCR-ALS) combined with Lasso regression reveals elastic fiber-derived (Ce1) and collagen fiber-derived (Cc6) components that are significantly increased in aTAA lesions of murine and human aortic tissues. In particular, Cc6 detects changes in amino acid residues, including phenylalanine, tyrosine, tryptophan, cysteine, aspartate, and glutamate. Ce1 and Cc6 may serve as diagnostic Raman biomarkers that detect alterations of amino acids derived from aneurysm lesions.


Asunto(s)
Aorta Torácica/patología , Aneurisma de la Aorta Torácica/patología , Aneurisma de la Aorta/patología , Biomarcadores/análisis , Espectrometría Raman , Disección Aórtica/patología , Animales , Aorta/patología , Rotura de la Aorta/patología , Humanos , Ratones , Espectrometría Raman/métodos , Estrés Mecánico , Resistencia a la Tracción/fisiología
11.
Br J Surg ; 108(6): 652-658, 2021 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-34157087

RESUMEN

BACKGROUND: Previous studies have suggested that finite element analysis (FEA) can estimate the rupture risk of an abdominal aortic aneurysm (AAA); however, the value of biomechanical estimates over measurement of AAA diameter alone remains unclear. This study aimed to compare peak wall stress (PWS) and peak wall rupture index (PWRI) in participants with ruptured and asymptomatic intact AAAs. METHODS: The reproducibility of semiautomated methods for estimating aortic PWS and PWRI from CT images was assessed. PWS and PWRI were estimated in people with ruptured AAAs and those with asymptomatic intact AAAs matched by orthogonal diameter on a 1 : 2 basis. Spearman's correlation coefficient was used to assess the association between PWS or PWRI and AAA diameter. Independent associations between PWS or PWRI and AAA rupture were identified by means of logistic regression analyses. RESULTS: Twenty individuals were included in the analysis of reproducibility. The main analysis included 50 patients with an intact AAA and 25 with a ruptured AAA. Median orthogonal diameter was similar in ruptured and intact AAAs (82·3 (i.q.r. 73·5-92·0) versus 81·0 (73·2-92·4) mm respectively; P = 0·906). Median PWS values were 286·8 (220·2-329·6) and 245·8 (215·2-302·3) kPa respectively (P = 0·192). There was no significant difference in PWRI between the two groups (P = 0·982). PWS and PWRI correlated positively with orthogonal diameter (both P < 0·001). Participants with high PWS, but not PWRI, were more likely to have a ruptured AAA after adjusting for potential confounders (odds ratio 5·84, 95 per cent c.i. 1·22 to 27·95; P = 0·027). This association was not maintained in all sensitivity analyses. CONCLUSION: High aortic PWS had an inconsistent association with greater odds of aneurysm rupture in patients with a large AAA.


Asunto(s)
Aneurisma de la Aorta Abdominal/complicaciones , Rotura de la Aorta/etiología , Anciano , Aorta Abdominal/fisiopatología , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/fisiopatología , Rotura de la Aorta/diagnóstico , Rotura de la Aorta/patología , Rotura de la Aorta/fisiopatología , Enfermedades Asintomáticas , Estudios de Casos y Controles , Femenino , Análisis de Elementos Finitos , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo
12.
J Biochem Mol Toxicol ; 35(8): e22836, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34075649

RESUMEN

The mortality rate in ruptured abdominal aortic aneurysms can today be reduced through cardiovascular surgery. However, ischemia and reperfusion-induced tissue damage develop due to aortic cross-clamping applied during surgery. The present study aimed to reduce oxidative stress-induced hepatic damage resulting from ischemia and reperfusion due to aortic cross-clamping during surgery by means of resveratrol administration. Forty male Sprague-Dawley rats were randomly assigned into four groups: control (healthy), glycerol+ischemia/reperfusion (I/R) (sham), I/R, and I/R + Resveratrol. In all groups scheduled for I/R, 60 min of shock was followed by 60 min of ischemia. In the I/R + Resveratrol group, 10 mg/kg of resveratrol was administered 15 min before ischemia and immediately before reperfusion via the intraperitoneal route. In addition, 120 min of reperfusion was applied under anesthesia after ischemia in all groups. Intralobar and interlobar necrosis, vascular congestion, and edematous fields resulting from aortic occlusion were present. Liver tissue malondialdehyde (MDA) levels and cleaved caspase-3 positivity increased, while glutathione (GSH) levels decreased. However, resveratrol administration reduced intralobular and interlobar necrosis, vascular congestion and edematous fields, cleaved caspase-3 positivity, and MDA levels, and increased GSH levels. Our findings suggest that resveratrol is effective against aortic occlusion-induced liver injury by reducing oxidative stress and apoptosis.


Asunto(s)
Aneurisma de la Aorta Abdominal/metabolismo , Rotura de la Aorta/metabolismo , Apoptosis/efectos de los fármacos , Hepatopatías/prevención & control , Estrés Oxidativo/efectos de los fármacos , Resveratrol/farmacología , Animales , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aneurisma de la Aorta Abdominal/patología , Rotura de la Aorta/complicaciones , Rotura de la Aorta/tratamiento farmacológico , Rotura de la Aorta/patología , Modelos Animales de Enfermedad , Hepatopatías/etiología , Hepatopatías/metabolismo , Hepatopatías/patología , Masculino , Ratas
13.
Am J Physiol Heart Circ Physiol ; 320(5): H1786-H1801, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33635167

RESUMEN

Thoracic aortic aneurysm and dissection (TAAD) is a deadly disease characterized by intimal disruption induced by hemodynamic forces of the circulation. The effect of exercise in patients with TAAD is largely unknown. ß-Aminopropionitrile (BAPN) is an irreversible inhibitor of lysyl oxidase that induces TAAD in mice. The objective of this study was to investigate the effect of aerobic exercise on BAPN-induced TAAD. Upon weaning, mice were given either BAPN-containing water or standard drinking water and subjected to either conventional cage activity (BAPN-CONV) or forced treadmill exercise (BAPN-EX) for up to 26 wk. Mortality was 23.5% (20/85) for BAPN-CONV mice versus 0% (0/22) for BAPN-EX mice (hazard ratio 3.8; P = 0.01). BAPN induced significant elastic lamina fragmentation and intimal-medial thickening compared with BAPN-untreated controls, and aneurysms were identified in 50% (5/10) of mice that underwent contrast-enhanced CT scanning. Exercise significantly decreased BAPN-induced wall thickening, calculated circumferential wall tension, and lumen diameter, with 0% (0/5) of BAPN-EX demonstrating chronic aortic aneurysm formation on CT scan. Expression of selected genes relevant to vascular diseases was analyzed by qRT-PCR. Notably, exercise normalized BAPN-induced increases in TGF-ß pathway-related genes Cd109, Smad4, and Tgfßr1; inflammation-related genes Vcam1, Bcl2a1, Ccr2, Pparg, Il1r1, Il1r1, Itgb2, and Itgax; and vascular injury- and response-related genes Mmp3, Fn1, and Vwf. Additionally, exercise significantly increased elastin expression in BAPN-treated animals compared with controls. This study suggests that moderate aerobic exercise may be safe and effective in preventing the most devastating outcomes in TAAD.NEW & NOTEWORTHY Moderate aerobic exercise was shown to significantly reduce mortality, extracellular matrix degradation, and thoracic aortic aneurysm and dissection formation associated with lysyl oxidase inhibition in a mouse model. Gene expression suggested a reversal of TGF-ß, inflammation, and extracellular matrix remodeling pathway dysregulation, along with augmented elastogenesis with exercise.


Asunto(s)
Aorta Torácica/patología , Aneurisma de la Aorta Torácica/terapia , Disección Aórtica/terapia , Rotura de la Aorta/prevención & control , Terapia por Ejercicio , Matriz Extracelular/patología , Remodelación Vascular , Aminopropionitrilo , Disección Aórtica/inducido químicamente , Disección Aórtica/metabolismo , Disección Aórtica/patología , Animales , Aorta Torácica/metabolismo , Aorta Torácica/fisiopatología , Aneurisma de la Aorta Torácica/inducido químicamente , Aneurisma de la Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/patología , Rotura de la Aorta/inducido químicamente , Rotura de la Aorta/metabolismo , Rotura de la Aorta/patología , Dilatación Patológica , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Regulación de la Expresión Génica , Hemodinámica , Masculino , Ratones Endogámicos C57BL , Proteolisis , Transducción de Señal
15.
Ann Vasc Surg ; 70: 517-527, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32891747

RESUMEN

BACKGROUND: Resistance and elasticity of normal and aneurysmal aorta walls are directly associated with this vessel's growth and rupture. This study aims to experimentally analyze the biomechanical behavior of aneurysmal specimens found at autopsy, comparing them with normal diameter aortas removed from age-matched donors. METHODS: Thirty-eight human aortas (30 normal aortas; 8 infrarenal abdominal aortic aneurysms) were harvested during autopsy. An apparatus was built with a digital gauge, plastic tray, connections, and hoses that conducted fluid (air) from a pump through the system. Specimens were dissected, and a flexible balloon was introduced in each of them to avoid leakage. The specimens were fastened on the test tray, and activation of the air pump enhanced system pressure up to their rupture. RESULTS: All 8 aneurysms and all 30 normal aortas specimens evolved to rupture under inflation pressures above 590 mm Hg (mean ± standard deviation = 1,035 ± 375 mm Hg) and 840 mm Hg (mean ± SD = 1,405 ± 342 mm Hg), respectively. In the aneurysm group, 25% of specimens did not rupture in their most dilated region. Percentage of increment in diameter was higher in normal aortas (mean ± SD = 0.2106 ± 0.144) than in aneurysms (mean ± SD = 0.093 ± 0.070). CONCLUSIONS: In the present experiment, unruptured infrarenal abdominal aortic aneurysms could support high pressures nearly as much as nonaneurysmal abdominal aortas. In some specimens, the most dilated part of the aneurysm was not the most vulnerable under pressure. Normal aortas presented higher elasticity than aneurysms.


Asunto(s)
Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/patología , Rotura de la Aorta/patología , Presión Arterial , Adulto , Anciano , Anciano de 80 o más Años , Aorta Abdominal/fisiopatología , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/fisiopatología , Rotura de la Aorta/etiología , Rotura de la Aorta/fisiopatología , Autopsia , Estudios de Casos y Controles , Dilatación Patológica , Elasticidad , Femenino , Humanos , Masculino , Persona de Mediana Edad
17.
PLoS One ; 15(11): e0242097, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33211767

RESUMEN

We present a data-informed, highly personalized, probabilistic approach for the quantification of abdominal aortic aneurysm (AAA) rupture risk. Our novel framework builds upon a comprehensive database of tensile test results that were carried out on 305 AAA tissue samples from 139 patients, as well as corresponding non-invasively and clinically accessible patient-specific data. Based on this, a multivariate regression model is created to obtain a probabilistic description of personalized vessel wall properties associated with a prospective AAA patient. We formulate a probabilistic rupture risk index that consistently incorporates the available statistical information and generalizes existing approaches. For the efficient evaluation of this index, a flexible Kriging-based surrogate model with an active training process is proposed. In a case-control study, the methodology is applied on a total of 36 retrospective, diameter matched asymptomatic (group 1, n = 18) and known symptomatic/ruptured (group 2, n = 18) cohort of AAA patients. Finally, we show its efficacy to discriminate between the two groups and demonstrate competitive performance in comparison to existing deterministic and probabilistic biomechanical indices.


Asunto(s)
Aneurisma de la Aorta Abdominal/patología , Rotura de la Aorta/patología , Modelos Teóricos , Modelación Específica para el Paciente , Aorta/diagnóstico por imagen , Aorta/patología , Rotura de la Aorta/epidemiología , Fenómenos Biomecánicos , Estudios de Casos y Controles , Femenino , Humanos , Masculino
18.
BMC Surg ; 20(1): 272, 2020 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-33160340

RESUMEN

BACKGROUND: Metastatic germ cell cancer of the testis is characterized by favorable prognosis since effective treatment methods are available even in cases of extensive disease. Retroperitoneal masses frequently encroach major blood vessels requiring a vascular intervention usually performed in association with the post-chemotherapy retroperitoneal lymph node dissection (RPLND). Reported clinical case describes a successful pre-treatment endovascular surgery for abdominal aortic rupture allowing for full-dose systemic chemotherapy administration, and subsequent radical surgical intervention at primary tumor site as well as metastatic retroperitoneal lymph node dissection including the reconstruction of inferior caval vein. CASE PRESENTATION: Patient presented with left-sided testicular tumor and voluminous retroperitoneal mass with vascular involvement. Soon after the patient had been admitted for the first cycle of cisplatin-based chemotherapy, computed tomographic angiography (CTA) revealed a dorsal aortic wall rupture with active extravasation and irregular pseudoaneurysmatic dilatation of the aorta below the leak area. Retroperitoneal intratumoral hemorrhage associated with the bilateral iliac venous thrombosis required an endovascular repair procedure of infrarenal abdominal aorta. CONCLUSIONS: Following the successful endovascular aortic repair 3 cycles of BEP (bleomycin, etoposide, cisplatin) regimen were administered with subsequent delayed left radical orchiectomy and RPLND associated with vena cava inferior (VCI) resection. Reconstruction of VCI was originally not deemed necessary as collateral blood flow appeared sufficient, however, intraoperative complications resulted in the need for unilateral VCI reconstruction, using the interposed bypass between right common iliac vein and infrarenal segment of VCI. Histopathologic examination of the attained specimen detected no vital cancer structures. The patient remains disease-free 18 months after the RPLND.


Asunto(s)
Rotura de la Aorta/cirugía , Procedimientos Endovasculares/métodos , Hemorragia/cirugía , Neoplasias de Células Germinales y Embrionarias , Neoplasias Retroperitoneales , Neoplasias Testiculares , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/patología , Aorta Abdominal/cirugía , Rotura de la Aorta/diagnóstico por imagen , Rotura de la Aorta/etiología , Rotura de la Aorta/patología , Bleomicina/administración & dosificación , Cisplatino/administración & dosificación , Angiografía por Tomografía Computarizada , Etopósido/administración & dosificación , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Humanos , Vena Ilíaca , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/secundario , Neoplasias de Células Germinales y Embrionarias/cirugía , Orquiectomía , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/secundario , Neoplasias Retroperitoneales/cirugía , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/patología , Neoplasias Testiculares/cirugía , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/secundario , Neoplasias Vasculares/cirugía , Vena Cava Inferior/cirugía , Trombosis de la Vena/cirugía
19.
Gene ; 762: 145056, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-32805313

RESUMEN

BACKGROUND: Abdominal aortic aneurysm (AAA) is a disease characterized by weakening arterial wall and permanent expansion with high mortality once rupture, which was involved with immune system activation. However, owing to technical difficulties, previous research has limited the impact of one or limited immune cells on AAA. METHODS: We analyzed the composition of immune cells using the CIBERSORT algorithm through transcriptome sequencing data from patients with stable (eAAA) and ruptured aneurysms (rAAA). The whole transcriptome sequencing data, including 17 patients with ruptured AAA and 31 patients with stable AAA were downloaded from Gene Expression Omnibus (GEO, GSE98278). After normalizing and data processing, five rAAA and seventeen eAAA patients entered the follow-up analysis. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify several pathways that were significantly enriched in rAAA compared to eAAA tissues. RESULTS: We demonstrated that the compositions of infiltrative immune cell in eAAA and rAAA were different. Naïve B cells, both resting and activated CD4+ memory T cells were found significantly higher in ruptured AAA, while memory B cells and activated mast cells were much less in ruptured AAA than that in stable AAA. Besides, PTX3 was significantly highly expressed in rAAA, which might be associated with the complement system and polarization of macrophages. Finally, differentially expressed genes and the related immune cells were mapped in a network to reveal the relationship between gene expression and infiltrative immune cells. CONCLUSION: We identified the infiltrated immune cell profile of eAAA and rAAA patients, which might be the potential target of AAA treatment.


Asunto(s)
Aneurisma de la Aorta Abdominal/genética , Rotura de la Aorta/genética , Linfocitos B/metabolismo , Linfocitos T/metabolismo , Transcriptoma , Animales , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Rotura de la Aorta/metabolismo , Rotura de la Aorta/patología , Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Células Dendríticas/metabolismo , Humanos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo
20.
Comput Math Methods Med ; 2020: 6718495, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32724330

RESUMEN

As many as 80% of patients with TAR die on the spot while out of those reaching a hospital, 30% would die within 24 hours. Thus, it is essential to better understand and prevent this injury. The exact mechanics of TAR are unknown. Although most researchers approve it as a common-sense deceleration injury, the exact detailed mechanism of TRA still remains unidentified. In this work, a deceleration mechanism of TAR was carried out using finite element analysis (FEA). The FE analysis aimed to predict internal kinematics of the aorta and assist to comprehend the mechanism of aorta injury. The model contains the heart, lungs, thoracic aorta vessel, and rib cage. High-resolution computerized tomography (HR CT scan) was used to provide pictures that were reconstructed by MIMICS software. ANSYS FE simulation was carried out to investigate the behavior of the aorta in the thoracic interior after deceleration occurred during a car crash. The finite element analysis indicated that maximum stress and strain applied to the aorta were from 5.4819e5 to 2.614e6 Pa and 0.21048 to 0.62676, respectively, in the Y-direction when the initial velocity increased from 10 to 25 m/s. Furthermore, in the X-direction when the velocity changed from 15 to 25 m/s, the stress and strain values increased from 5.17771e5 to 2.3128e6 and from 0.22445 to 0.618, respectively.


Asunto(s)
Aorta/lesiones , Rotura de la Aorta/etiología , Modelos Cardiovasculares , Contusiones Miocárdicas/etiología , Aceleración/efectos adversos , Accidentes de Tránsito , Rotura de la Aorta/patología , Rotura de la Aorta/fisiopatología , Fenómenos Biomecánicos , Biología Computacional , Simulación por Computador , Análisis de Elementos Finitos , Humanos , Imagenología Tridimensional , Conceptos Matemáticos , Contusiones Miocárdicas/patología , Contusiones Miocárdicas/fisiopatología , Estrés Mecánico , Tomografía Computarizada por Rayos X
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...