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1.
Biochem Pharmacol ; 173: 113749, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31830469

RESUMO

Omega-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to protect the cardiovascular system, in part, by stimulating the endothelial formation of nitric oxide (NO). EPA:DHA 6:1 has been identified as a potent omega 3 PUFA formulation to induce endothelium-dependent vasorelaxation and activation of endothelial NO synthase (eNOS). This study examined whether intake of EPA:DHA 6:1 (500 mg/kg/day) for 2 weeks improves an established endothelial dysfunction in old rats (20 months old), and, if so, the underlying mechanism was subsequently determined. In the main mesenteric artery rings, an endothelial dysfunction characterized by a blunted NO component, an abolished endothelium-dependent hyperpolarization component, and increased endothelium-dependent contractile responses (EDCFs) are observed in old rats compared to young rats. Age-related endothelial dysfunction was associated with increased vascular formation of reactive oxygen species (ROS) and expression of eNOS, components of the local angiotensin system, senescence markers, and cyclooxygenase-2 (COX-2), and the downregulation of COX-1. The EPA:DHA 6:1 treatment improved the NO-mediated relaxation, reduced the EDCF-dependent contractile response and the vascular formation of ROS, and normalized the expression level of all target proteins in the old arterial wall. Thus, the present findings indicate that a 2-week intake of EPA:DHA 6:1 by old rats restored endothelium-dependent NO-mediated relaxations, most likely, by preventing the upregulation of the local angiotensin system and the subsequent formation of ROS.


Assuntos
Endotélio Vascular/fisiologia , Ácidos Graxos Ômega-3/administração & dosagem , Artérias Mesentéricas/fisiologia , NADPH Oxidases/metabolismo , Peptidil Dipeptidase A/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Fatores Etários , Animais , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/química , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/química , Ácidos Graxos Ômega-3/química , Imunofluorescência , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Ratos Wistar , Proteína Supressora de Tumor p53/metabolismo , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
3.
Int J Cardiol ; 226: 103-109, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27806307

RESUMO

BACKGROUND: This study aimed to provide safety and efficacy data of rivaroxaban in routine patient care in a non-selected symptomatic venous thromboembolism (VTE) population. METHODS AND RESULTS: REMOTEV is a prospective, non-interventional study of patients with acute symptomatic VTE, treated with oral rivaroxaban, VKA or parenteral heparin/fondaparinux alone for at least 3months and who are followed up for 6months. From Nov. 2013 to July 2015, 499 consecutive patients were retained for baseline analysis and 445 for safety analysis. The mean age was 65.1years, 7.6% had previously known active cancer, 18.6% had creatinine clearance 30≤CrCl<60mL/min, and 87.8% had pulmonary embolism with or without deep venous thrombosis. The major and clinically relevant bleeding rate was 5.4% (15/280) in the rivaroxaban group, 9.4%/(9/96) in the VKA group and 7.2% (5/69) in the heparin/fondaparinux group. The recurrent VTE rate was 1.4% (4/280) in the rivaroxaban group, 3.1% (3/96) in the VKA group and 11.6% (8/69) in the heparin/fondaparinux group. In the propensity score-adjusted samples, major and clinically relevant non-major bleeding (HR 0.37 [95% CI, 0.15 to 0.93], p<0.05), all-cause death (HR 0.21 [95% CI, 0.06 to 0.66], p<0.01) and the composite of recurrent VTE, major and clinically relevant non-major bleeding and all-cause mortality (HR 0.35 [95% CI, 0.17 to 0.71], p<0.01), were significantly lower in the rivaroxaban group compared to the VKA group. CONCLUSION: In REMOTEV 6-month outcomes are consistent with the findings of the phase 3 randomized trials and post-marketing data, with low rates of major bleeding and symptomatic recurrent VTE.


Assuntos
Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/epidemiologia
4.
Arch Cardiovasc Dis ; 109(11): 634-640, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27692662

RESUMO

Non-vitamin K antagonist oral anticoagulants are becoming increasingly important in the prophylaxis and treatment of thrombosis in atrial fibrillation and venous thromboembolism. Antiplatelets are widely prescribed in the primary and secondary prevention of cardiac and vascular diseases. There are potentially numerous situations where anticoagulants and antiplatelets may be combined; these combinations have been explored in coronary artery disease, and some have been included in updated recommendations. Is it legitimate to transpose these recommendations to the management of peripheral artery disease? The specific characteristics of the treated vessels, the stents used, the respective frequencies of stent thrombosis and its effect on the target organ are probably different, and explain why opinions differ. However, because of a lack of evidence, empirical behaviours are being established without scientific validation. This review of the literature details the situations in which combinations of an anticoagulant and an antiplatelet have been explored in peripheral artery disease. We discuss the issue of antithrombotic combinations in stable peripheral artery disease and for vascular or endovascular surgery.


Assuntos
Anticoagulantes/administração & dosagem , Doença Arterial Periférica/prevenção & controle , Inibidores da Agregação Plaquetária/administração & dosagem , Prevenção Secundária/métodos , Vitamina K/antagonistas & inibidores , Administração Oral , Quimioterapia Combinada , Humanos
5.
Ann Vasc Surg ; 32: 5-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26802302

RESUMO

BACKGROUND: Use of the forearm basilic vein for the creation of an arteriovenous fistula has been codified as second-choice vascular access for hemodialysis in the last clinical guidelines of the Society for Vascular Surgery in 2008. Poor literature data on this technical option and on its evaluation and outcomes led us to initiate a retrospective single-center study. METHODS: We analyzed the outcomes of every arteriovenous fistula using the forearm basilic vein created in our department. It is a retrospective study in which we collected data prospectively by contacting dialysis centers, nephrologists, and patients. Primary end point was primary patency rate at 1 year. Secondary end points were secondary patency rate at 1 year, time of maturation, and Doppler flow measurement before the first puncture. RESULTS: From February 2004 to June 2014, 49 forearm basilic arteriovenous fistulas were created: 33 ulnar-basilic and 16 radial basilic arteriovenous fistulas. Initial technical success rate was 98%. Functional success rate was 60%. Primary and secondary patency rates at 1 year were respectively 21% and 48%. Median time of maturation was 81 days, and mean Doppler flow measurement was 678 mL/min. Ulnar-basilic fistulas had a statistically significant shorter time of maturation than radial basilic fistulas (P ≤ 0.05). CONCLUSIONS: Despite poor primary patency rate and a long time of maturation, forearm basilic arteriovenous fistula has satisfactory secondary patency rate and keeps all the advantages of a distal-located vascular access concerning complications. It is worth its second-choice place in the current algorithm of creation of vascular access for hemodialysis.


Assuntos
Derivação Arteriovenosa Cirúrgica/métodos , Artéria Braquial/cirurgia , Antebraço/irrigação sanguínea , Artéria Radial/cirurgia , Diálise Renal , Insuficiência Renal Crônica/terapia , Veias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Feminino , França , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Artéria Radial/diagnóstico por imagem , Artéria Radial/fisiopatologia , Fluxo Sanguíneo Regional , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler , Grau de Desobstrução Vascular , Veias/diagnóstico por imagem , Veias/fisiopatologia , Adulto Jovem
6.
Ann Vasc Surg ; 32: 25-33, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26806233

RESUMO

BACKGROUND: The aim was to report the midterm outcome for nonagenarians with critical limb ischemia (CLI) and to identify factors affecting survival or limb salvage rates. METHODS: Nonagenarians who underwent endovascular surgery (ES), open surgery (OS), or primary amputation (PA) for CLI between 2005 and 2014 were included. Cox regression model identified factors affecting survival and limb salvage. RESULTS: ES was performed in 116 patients (119 limbs), OS in 73 patients (73 limbs), and PA in 54 patients (57 limbs). Mean follow-up was 10.38 months. There was no difference in survival between ES, OS, and PA groups: survival rate was 51.2% at 1 year and 38.9% at 2 years after ES, 48.3% at 1 year and 39.6% at 2 years after OS, and 50.6% at 1 years and 40.8% at 2 years after PA (P = 0.58). There was no difference in limb salvage between ES and OS groups: limb salvage rate was 88.2% and 77.8% at 1 and 2 years after ES and 87.3% and 77.6% at 1 and 2 years after OS. Coronary artery disease (hazard ratio [HR] 1.54; confidence interval [CI] 1.04-1.08; P = 0.01) was risk factor for death. Fully dependent state was risk factor for death (HR 4.2; CI 3.55-4.87; P < 0.001) and major amputation (HR 5.3; CI 1.32-1.67; P < 0.001). In fully dependent patients, 1-year and 2-year survival rate was 28.9% and 20.6%, respectively, and 1-year and 2-year limb salvage rate was 61.2% and 44.5%, respectively. CONCLUSIONS: With acceptable early and late mortality, limb salvage and maintenance of functional status and level of independent living, revascularization in nonagenarians is effective as long as the patient is not fully dependent.


Assuntos
Amputação Cirúrgica , Procedimentos Endovasculares , Isquemia/cirurgia , Procedimentos Cirúrgicos Vasculares , Atividades Cotidianas , Fatores Etários , Idoso de 80 Anos ou mais , Amputação Cirúrgica/efeitos adversos , Amputação Cirúrgica/mortalidade , Distribuição de Qui-Quadrado , Estado Terminal , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Vida Independente , Isquemia/diagnóstico por imagem , Isquemia/mortalidade , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
7.
Ann Vasc Surg ; 29(2): 365.e5-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25463334

RESUMO

Patients with Crohn disease (CD) or ulcerative colitis are known to be at increased risk of arterial thromboembolic complications. We report the case of a 33-year-old woman suffering from CD for 19 years who presented lower limb claudication. Computed tomography scan revealed an aortoiliac occlusion extending from the level of the inferior mesenteric artery to both iliac bifurcations. Endovascular recanalization was attempted as a first option but failed. We then performed an aortobi-femoral bypass through a left retroperitoneal approach that allowed a total relief of the symptoms. Histologic study of the aorta demonstrated a nonspecific aortitis with lymphohistiocytic cell infiltration in the media and adventitia tunica. There was no signs of associated vasculitis. At the light of a literature review, we discussed our surgical strategy and the inflammation of the aortic wall as local factor of thrombosis that has never been previously described.


Assuntos
Doenças da Aorta/diagnóstico , Arteriopatias Oclusivas/diagnóstico , Doença de Crohn/complicações , Trombose/diagnóstico , Adulto , Doenças da Aorta/etiologia , Doenças da Aorta/terapia , Aortite/diagnóstico , Aortite/etiologia , Aortite/terapia , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/terapia , Implante de Prótese Vascular , Feminino , Humanos , Extremidade Inferior/irrigação sanguínea , Trombose/etiologia , Trombose/terapia
8.
Ann Vasc Surg ; 28(4): 983-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24333196

RESUMO

BACKGROUND: We compared long-term outcomes of isolated below-the-knee (BTK) bypass revascularization in diabetic patients presenting with critical limb ischemia (CLI) with and without achieving the bypass on the artery corresponding to the territory of the lesion based on the angiosome concept. MATERIALS: We analyzed outcomes of 58 consecutive CLI limbs of 54 diabetic patients presenting with tissue loss who underwent isolated BTK bypasses from 2003 to 2009 for crural occlusive arterial disease. Bypasses were classified into direct and indirect groups based on the angiosome concept, whether feeding artery flow to the site of ischemic tissue loss was achieved or not. We compared median ulcer-healing time, survival, primary patency, and limb salvage rates between both groups by Kaplan-Meier analysis and log-rank test. Independent factors of major amputations were explored by univariate analysis. Variables with P < 0.2 in univariate analysis were submitted to multivariable analysis. RESULTS: Median ulcer-healing time was 56 ± 18 days in direct group (n = 36) and 112 ± 45 days in indirect group (n = 22, P = 0.01). There was no difference between both groups in terms of survival or primary patency. Limb salvage rate was significantly higher in direct group than in indirect group: 91% vs. 66% at 1 year, 65% vs. 24% at 3 years, and 58% vs. 18% at 5 years, respectively (P = 0.03). After multivariable Cox proportional analysis, independent factors associated with major amputation were end-stage renal disease (P = 0.030) and C-reactive protein level (P = 0.025). CONCLUSIONS: Achieving a direct arterial flow based on angiosome concept in CLI diabetic patients presenting with tissue loss appears to be important for ulcer healing and limb salvage.


Assuntos
Pé Diabético/cirurgia , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Modelos Anatômicos , Modelos Cardiovasculares , Doença Arterial Periférica/cirurgia , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Distribuição de Qui-Quadrado , Estado Terminal , Pé Diabético/diagnóstico , Pé Diabético/fisiopatologia , Feminino , Humanos , Isquemia/diagnóstico , Isquemia/fisiopatologia , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Modelos de Riscos Proporcionais , Fluxo Sanguíneo Regional , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Cicatrização
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