RESUMO
BACKGROUND: Prediabetes (PDM) and diabetes mellitus (DM) are common among acute coronary syndrome (ACS) patients. The present study evaluated the association between diabetes status and radial artery (RA) atherosclerosis using optical coherence tomography (OCT) in ACS patients. METHODS: A total of 335 ACS patients who underwent RA OCT were categorized into the DM group, the PDM group, and the normal glucose metabolism (NGM) group. OCT characteristics and clinical variables were compared. RESULTS: RA atherosclerotic plaques were more frequent in the PDM and DM groups than in the NGM group (38.7% vs. 33.3% vs. 16.1%, p = 0.001). Lipid and calcified plaque occurrence were significantly more common in the DM group, followed by the PDM and NGM groups (19.3% vs. 14.6% vs. 6.5%, p = 0.027; 11.8% vs. 6.5% vs. 1.1%, p = 0.009). The prevalence of microvessels in the PDM group was significantly higher (42.7% vs 23.7%, p = 0.017) than in the NGM group but was comparable to the DM group. Multivariate analysis revealed that HbA1c level and age were independent predictors of RA plaque formation and eccentric intimal hyperplasia (all p<0.05). CONCLUSIONS: RA atherosclerosis characteristics differ according to diabetes status. HbA1c level could be a useful marker for RA atherosclerosis progression in ACS patients.
Assuntos
Síndrome Coronariana Aguda , Aterosclerose , Doença da Artéria Coronariana , Diabetes Mellitus , Placa Aterosclerótica , Estado Pré-Diabético , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/epidemiologia , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/metabolismo , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Hemoglobinas Glicadas/metabolismo , Humanos , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Artéria Radial/diagnóstico por imagem , Artéria Radial/metabolismo , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodosRESUMO
We investigated the sensitivity, specificity and safety of ergonovine provocation test of radial artery in the diagnosis of coronary artery spasm (CAS). The patients who came to our hospital for chest pain from January to June 2020 as well as had coronary stenosis < 50% and no radial artery stenosis, were enrolled in this study. These patients were divided into CAS group and control group after intracoronary ergonovine provocation test. All patients underwent ergonovine provocation test of radial artery, the inner diameter (D0 and D1) and the peak systolic velocities (PSV0 and PSV1) of the radial artery were measured by ultrasound before and after ergonovine provocation. The predictive value of ergonovine provocation test of radial artery for the diagnosis of CAS was analyzed using receiver operator characteristic (ROC) curve. There were 19 patients in the CAS group and 28 patients in the control group. Low density lipoprotein cholesterol and smoking rate were significantly higher in the CAS group than in the control group (all P < 0.05), but there were no significant differences in other items (P > 0.05) between the two groups. In the ergonovine provocation test of radial artery, degree of radial artery stenosis was significantly higher in the CAS group [41.50% (35.60%, 50.00%)] than in the control group [11.25% (5.15%, 23.00%)] (P = 0.000), but there were no siginificant differences in D0, PSV0 and PSV1 between the two groups (P > 0.05). The area under ROC curve of ergonovine (120 µg) provocation test of radial artery for the diagnosis of CAS was 0.912 with 95%CI: 0.792-0.975, P = 0.001, cut-off of 31%, specificity of 92.86% and sensitivity of 84.21%. The ergonovine (120 µg) provocation test of radial artery did not cause any adverse reactions. We concluded that the ergonovine provocation test of radial artery has high sensitivity, specificity and safety in the diagnosis of CAS.
Assuntos
Vasoespasmo Coronário/diagnóstico , Vasos Coronários/efeitos dos fármacos , Ergonovina/farmacologia , Área Sob a Curva , Dor no Peito/fisiopatologia , Angiografia Coronária/métodos , Vasos Coronários/metabolismo , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial/efeitos dos fármacos , Artéria Radial/metabolismo , Sensibilidade e Especificidade , Espasmo/diagnóstico , Espasmo/fisiopatologiaRESUMO
BACKGROUND: The aim of this study was to explore the impact of 6-Fr and 7-Fr sheaths on the incidence of long-term radial artery occlusion (RAO) after trans-radial coronary intervention (TRI). METHODS: From September 2013 to January 2016, patients with ischemic heart disease including acute myocardial infarction and true bifurcation lesions were randomly assigned to 6-Fr group and 7-Fr group immediately after coronary angiography in a 1:1 ratio. The radial artery diameters were observed by ultrasound examination one day prior to TRI as well as at 30 days and 1 year after TRI. The primary endpoint was the incidence of RAO at 1-year after TRI. The secondary endpoints were the incidence of local vascular complications during hospitalization and changes of radial artery diameters within 1-year after TRI between the two groups. Additionally, multivariate logistic regression analysis was used to explore potential factors related to the incidence of long-term RAO after TRI. RESULTS: A total of 214 patients were enrolled and randomly assigned to 6-Fr group (n = 105) or 7-Fr group (n = 109). There was no significant difference in the incidence of RAO at 1-year after TRI (8.57% vs. 12.84%, p = 0.313). Moreover, no significant difference was observed in the incidence of local vascular complications during hospitalization (20% vs. 24.77%, p = 0.403). After 1-year follow-up, no significant difference was found in radial artery diameters (2.63 ± 0.31 mm vs. 2.64 ± 0.27 mm, p = 0.802). Multivariate logistic analysis revealed that repeated TRI was an independent risk factor of long-term RAO 1 year after TRI (OR = 10.316, 95% CI 2.928-36.351, p = 0.001). CONCLUSIONS: Compared to 6-Fr sheath, 7-Fr sheath did not increase short-term or long-term incidence of RAO after TRI.
Assuntos
Arteriopatias Oclusivas , Intervenção Coronária Percutânea , Artéria Radial/metabolismo , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Cateterismo Cardíaco , Humanos , Estudos ProspectivosRESUMO
OBJECTIVE: Investigate the effects of photobiomodulation (PBM) on the expression of IL-10 and nitrites in individuals with Relapsing-Remitting multiple sclerosis (MS), as these biomarkers play a fundamental role in the physiopathology of the disease. The modulation of IL-10 and nitrites through treatment with PBM may be a novel treatment modality for MS. METHODS: A randomized, uncontrolled, clinical trial was conducted involving 14 individuals with a diagnosis of Relapsing-Remitting MS and a score of up to 6.0 on the Expanded Disability Status Scale (EDSS). THE PARTICIPANTS WERE RANDOMIZED TO TWO GROUPS: Group 1 -PBM in the sublingual region; Group 2 -PBM over the radial artery. Irradiation was administered with a wavelength of 808 nm and output power of 100 mW for 360 seconds twice a week, totaling 24 sessions. Peripheral blood was analyzed for the determination of serum levels of IL-10 and nitrites. RESULTS: After treatment with PBM, the expression of IL-10 increased in both the sublingual group (pre-treatment: 2.8 ± 1.4 pg/ml; post-treatment: 8.3 ± 2.4 pg/ml) and the radial artery group (pre-treatment: 2.7 pg/ml ± 1.4; post-treatment: 11.7 ± 3.8 pg/ml). In contrast, nitrite levels were not modulated in the sublingual group (pre-treatment: 65 ± 50 nmol/mg protein; post-treatment: 51 ± 42 nmol/mg protein) or the radial artery group (pre-treatment: 51 ± 16 nmol/mg protein; post-treatment: 42 ± 7 nmol/mg protein). CONCLUSION: Treatment with PBM positively modulated the expression of IL-10 but had no effect on nitrite levels. Further studies should be conducted with a larger sample and a control group, as PBM may be a promising complementary treatment for the management of MS. This trial is registered at ClinicalTrials.gov. Identifier: NCT03360487.
Assuntos
Interleucina-10/metabolismo , Terapia com Luz de Baixa Intensidade , Esclerose Múltipla Recidivante-Remitente/radioterapia , Nitritos/metabolismo , Adulto , Feminino , Humanos , Lasers Semicondutores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/patologia , Nitritos/sangue , Modalidades de Fisioterapia , Artéria Radial/metabolismo , Artéria Radial/efeitos da radiação , Adulto JovemRESUMO
The regulation of intracellular pH (pHi) plays a vital role in various cellular functions. We previously demonstrated that three different acid extruders, the Na+-H+ exchanger (NHE), Na+-HCO3- co-transporter (NBC) and H+-linked monocarboxylate transporter (MCT), functioned together in cultured human radial artery smooth muscle cells (HRASMCs). However, the functions of acid-loading transporters in HRASMCs remain poorly understood. Urotensin II (U-II), one of the most potent vasoconstrictors, is highly expressed in many cardiovascular diseases. The aim of this present study was to determine the concentration effect of U-II (3â¯pMâ¼100â¯nM) on the functional activity of pHi regulators in HRASMCs. Cultured HRASMCs were derived from segments of human radial arteries obtained from patients undergoing bypass grafting. Changes in pHi recovery due to intracellular acidification and alkalization induced by NH4Cl prepulse and Na-acetate prepulse, respectively, were detected by microspectrofluorimetry with the pH-sensitive fluorescent dye BCECF. Our present study showed that (a) U-II increased the activity of NHE in a concentration-dependent manner but did not change that of NBC or MCT or resting pHi, (b) the Cl--OH- exchanger (CHE) facilitated base extrusion, and (c) U-II induced a concentration-dependent increase in the activity of CHE. In conclusion, for the first time, our results highlight a concentration-dependent increase in the activity of NHE and CHE, but not NBC and MCT, induced by U-II in HRASMCs.
Assuntos
Miócitos de Músculo Liso/efeitos dos fármacos , Artéria Radial/efeitos dos fármacos , Urotensinas/farmacologia , Citoplasma/metabolismo , Relação Dose-Resposta a Droga , Humanos , Concentração de Íons de Hidrogênio , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Artéria Radial/citologia , Artéria Radial/metabolismo , Artéria Radial/fisiologia , Trocadores de Sódio-Hidrogênio/metabolismoRESUMO
BACKGROUND: Endothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. PATIENTS: 80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-ß (TGF-ß), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. RESULTS: After adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1-3 of RACs correlated with sTM (Râ¯=â¯0.50, pâ¯=â¯0.017), while grade 3 RACs were significantly associated with higher sTM (pâ¯=â¯0.02) than less advanced lesions. CONCLUSION: Among novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.
Assuntos
Células Endoteliais/metabolismo , Células Endoteliais/patologia , Inflamação/patologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Osteopontina/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Idoso , Biomarcadores/sangue , Calcinose/sangue , Doenças Cardiovasculares/sangue , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial/metabolismo , Artéria Radial/patologia , Análise de Regressão , Diálise Renal , Fatores de Risco , Trombomodulina/sangueRESUMO
Background Endothelial insulin resistance is insulin-insensitivity in the vascular endothelium and can be observed in experimental models. This study aimed to investigate endothelial insulin resistance in patients with suspected coronary artery disease. To this end, a novel method of obtaining freshly isolated arterial endothelial cells from a radial catheter sheath was developed. Methods and Results Freshly isolated arterial endothelial cells were retrieved from catheter sheaths placed in radial arteries for coronary angiography (n=69, patient age 64±12 years). The endothelial cells were divided into groups for incubation with or without insulin, vascular endothelial growth factor, or acetylcholine. The intensity of phosphorylated endothelial nitric oxide synthase at Ser1177 (p- eNOS ) was quantified by immunofluorescence microscopy. The percentage increase of insulin-induced phosphorylated endothelial nitric oxide synthase correlated negatively with derivatives of reactive oxygen metabolites, an oxidative stress test ( r=-0.348, n=53, P=0.011), E/E', an index of left ventricular diastolic dysfunction in Doppler echocardiography (ρ=-0.374, n=49, P=0.008), and log-transformed brain natriuretic peptide ( r=-0.266, n=62, P=0.037). Furthermore, percentage increase of insulin-induced p- eNOS was an independent factor for the cardio-ankle vascular index (standardized coefficient ß=-0.293, n=42, P=0.021) in the multivariate regression analysis of adaptive least absolute shrinkage and selection operator. Conclusions Our results suggested that endothelial insulin resistance is associated with oxidative stress, left ventricular diastolic dysfunction, heart failure, and arterial stiffness.
Assuntos
Doença da Artéria Coronariana/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Resistência à Insulina/fisiologia , Insulina/farmacologia , Artéria Radial/patologia , Vasodilatação/fisiologia , Cateterismo Cardíaco , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Ecocardiografia Doppler , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Óxido Nítrico Sintase/metabolismo , Artéria Radial/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: This pathophysiological study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetes. METHODS AND RESULTS: Radial artery endothelium-dependent flow-mediated dilatation in response to hand skin heating was reduced in essential hypertensive patients (n = 9) and type 2 diabetic subjects with (n = 19) or without hypertension (n = 10) compared to healthy subjects (n = 36), taking into consideration cardiovascular risk factors, flow stimulus and endothelium-independent dilatation to glyceryl trinitrate. Diabetic patients but not non-diabetic hypertensive subjects displayed elevated whole blood reactive oxygen species levels and loss of NO release during heating, assessed by measuring local plasma nitrite variation. Moreover, plasma levels of EET regioisomers increased during heating in healthy subjects, did not change in hypertensive patients and decreased in diabetic patients. Correlation analysis showed in the overall population that the less NO and EETs bioavailability increases during heating, the more flow-mediated dilatation is reduced. The expression and activity of sEH, measured in isolated peripheral blood mononuclear cells, was elevated in diabetic but not hypertensive patients, leading to increased EETs conversion to DHETs. Finally, hyperglycemic and hyperinsulinemic euglycemic clamps induced a decrease in flow-mediated dilatation in healthy subjects and this was associated with an altered EETs release during heating. CONCLUSIONS: These results demonstrate that an increased EETs degradation by sEH and altered NO bioavailability are associated with conduit artery endothelial dysfunction in type 2 diabetic patients independently from their hypertensive status. The hyperinsulinemic and hyperglycemic state in these patients may contribute to these alterations. Trial registration NCT02311075. Registered December 8, 2014.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Eicosanoides/sangue , Hipertensão Essencial/sangue , Artéria Radial/metabolismo , Vasodilatação , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/fisiopatologia , Epóxido Hidrolases/metabolismo , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/fisiopatologia , Feminino , Humanos , Hipertermia Induzida , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Nitritos/sangue , Nitroglicerina/administração & dosagem , Artéria Radial/efeitos dos fármacos , Artéria Radial/fisiopatologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagemRESUMO
BACKGROUND: An imbalance between the activity of matrix metalloproteinases (MMPs), particularly gelatinases, and tissue inhibitors of metalloproteinases (TIMPs) is considered as one of the mechanisms leading to aortocoronary graft failure. AIM: We aimed to assess the variability in gelatinase expression in the walls of aortocoronary conduits and to evaluate its impact on coronary artery bypass grafting (CABG) outcomes. METHODS: The study included 101 consecutive patients (61 men and 40 women) who underwent CABG. An immunohisto-chemical analysis of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression was performed on the cross-sections of the internal thoracic artery (ITA), radial artery (RA), and saphenous vein (SV). The histological findings were compared between patients with SV graft disease (SVGD[+] group) and those without occlusions in the SV (SVGD[-] group). RESULTS: The median MMP and TIMP expression was the weakest in the ITA wall. MMP expression was comparable between the RA and SV cross-sections, whereas TIMP expression was stronger in the RA than in the SV wall (p < 0.05). In most SV segments, but not in the arteries, immunostaining intensity for MMP was comparable to or stronger than for TIMPs. In the veins harvested from the SVGD(+) group, MMP-2 and MMP-9 tissue expression was more pronounced than in the SVGD(-) group. TIMP levels were comparable between groups. CONCLUSIONS: Imbalance in the metalloproteinase-to-inhibitor tissue expression in the vessel wall might predispose to graft failure. A stronger expression of TIMPs than MMPs in the arterial grafts might explain favourable long-term outcomes.
Assuntos
Vasos Sanguíneos/enzimologia , Ponte de Artéria Coronária , Doença das Coronárias/enzimologia , Gelatinases/genética , Inibidores Teciduais de Metaloproteinases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/metabolismo , Doença das Coronárias/genética , Doença das Coronárias/metabolismo , Doença das Coronárias/cirurgia , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial/enzimologia , Artéria Radial/metabolismo , Veia Safena/enzimologia , Veia Safena/metabolismo , Artérias Torácicas/enzimologia , Artérias Torácicas/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Resultado do TratamentoRESUMO
Adaptive remodeling processes are essential to the maintenance and viability of coronary artery bypass grafts where clinical outcomes depend strongly on the tissue source. In this investigation, we utilized an ex vivo perfusion bioreactor to culture porcine analogs of common human bypass grafts: the internal thoracic artery (ITA), the radial artery (RA), and the great saphenous vein (GSV), and then evaluated samples acutely (6 h) and chronically (7 days) under in situ or coronary-like perfusion conditions. Although morphologically similar, primary cells harvested from the ITA illustrated lower intimal and medial, but not adventitial, cell proliferation rates than those from the RA or GSV. Basal gene expression levels were similar in all vessels, with only COL3A1, SERPINE1, FN1, and TGFB1 being differentially expressed prior to culture; however, over half of all genes were affected nominally by the culturing process. When exposed to coronary-like conditions, RAs and GSVs experienced pathological remodeling not present in ITAs or when vessels were studied in situ. Many of the remodeling genes perturbed at 6 h were restored after 7 days (COL3A1, FN1, MMP2, and TIMP1) while others (SERPINE1, TGFB1, and VCAM1) were not. The findings elucidate the potential mechanisms of graft failure and highlight strategies to encourage healthy ex vivo pregraft conditioning.
Assuntos
Artéria Torácica Interna/patologia , Perfusão , Artéria Radial/patologia , Veia Safena/patologia , Técnicas de Cultura de Tecidos , Remodelação Vascular , Animais , Reatores Biológicos , Proliferação de Células , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Artéria Torácica Interna/metabolismo , Perfusão/instrumentação , Artéria Radial/metabolismo , Veia Safena/metabolismo , Transdução de Sinais , Sus scrofa , Fatores de Tempo , Técnicas de Cultura de Tecidos/instrumentação , Remodelação Vascular/genéticaRESUMO
BACKGROUND AND AIMS: The mechanisms involved in endothelial dysfunction in humans during aging are largely unknown at the level of conduit arteries. We aimed to asses the role of NO and CYP450 epoxygenases-derived epoxyeicosatrienoic acids (EETs) in the regulation of endothelium-dependent flow-mediated dilatation of conduit arteries during aging. METHODS: Radial artery diameter and mean wall shear stress were determined by echotracking coupled with Doppler in 83 subjects (19-71 years old) during a sustained flow increase induced by hand skin heating, with the brachial infusion of saline or NO-synthase and cytochrome P450 epoxygenase inhibitors (L-NNMA and fluconazole respectively). Local blood sampling was performed for the quantification of NO metabolite nitrite and EETs. RESULTS: The magnitude of flow-mediated dilatation was independently and negatively correlated with age, baseline artery diameter and systolic blood pressure, and positively correlated with the increase in shear stress induced by heating. There was an increase in nitrite level during heating until the age of 35-40 years, which declined thereafter. However, the inhibitory effect of L-NMMA on flow-mediated dilatation progressively decreased during aging, demonstrating a decrease in functional NO availability. Moreover, aging progressively reduced the increase in EET level during heating as well as the inhibitory effect of fluconazole on flow-mediated dilatation. CONCLUSIONS: These results show that aging impairs the availability of EETs and NO and epoxyeicosatrienoic acids in peripheral conduit arteries, contributing to the development of endothelial dysfunction.
Assuntos
Envelhecimento/sangue , Eicosanoides/sangue , Endotélio Vascular/metabolismo , Óxido Nítrico/metabolismo , Doença Arterial Periférica/sangue , Artéria Radial/metabolismo , Vasodilatação , Adulto , Fatores Etários , Idoso , Inibidores das Enzimas do Citocromo P-450/administração & dosagem , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Fluconazol/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Nitritos/sangue , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Artéria Radial/diagnóstico por imagem , Artéria Radial/efeitos dos fármacos , Artéria Radial/fisiopatologia , Ultrassonografia Doppler , Vasodilatação/efeitos dos fármacos , Adulto Jovem , ômega-N-Metilarginina/administração & dosagemRESUMO
BACKGROUND: Cerebral oximetry (cerebral oxygen saturation; ScO2) is used to noninvasively monitor cerebral oxygenation. ScO2 readings are based on the fraction of reduced and oxidized hemoglobin as an indirect estimate of brain tissue oxygenation and assume a static ratio of arterial to venous intracranial blood. Conditions that alter cerebral blood flow, such as acute changes in PaCO2, may decrease accuracy. We assessed the performance of two commercial cerebral oximeters across a range of oxygen concentrations during normocapnia and hypocapnia. METHODS: Casmed FORE-SIGHT Elite (CAS Medical Systems, Inc., USA) and Covidien INVOS 5100C (Covidien, USA) oximeter sensors were placed on 12 healthy volunteers. The fractional inspired oxygen tension was varied to achieve seven steady-state levels including hypoxic and hyperoxic PaO2 values. ScO2 and simultaneous arterial and jugular venous blood gas measurements were obtained with both normocapnia and hypocapnia. Oximeter bias was calculated as the difference between the ScO2 and reference saturation using manufacturer-specified weighting ratios from the arterial and venous samples. RESULTS: FORE-SIGHT Elite bias was greater during hypocapnia as compared with normocapnia (4 ± 9% vs. 0 ± 6%; P < 0.001). The INVOS 5100C bias was also lower during normocapnia (5 ± 15% vs. 3 ± 12%; P = 0.01). Hypocapnia resulted in a significant decrease in mixed venous oxygen saturation and mixed venous oxygen tension, as well as increased oxygen extraction across fractional inspired oxygen tension levels (P < 0.0001). Bias increased significantly with increasing oxygen extraction (P < 0.0001). CONCLUSIONS: Changes in PaCO2 affect cerebral oximeter accuracy, and increased bias occurs with hypocapnia. Decreased accuracy may represent an incorrect assumption of a static arterial-venous blood fraction. Understanding cerebral oximetry limitations is especially important in patients at risk for hypoxia-induced brain injury, where PaCO2 may be purposefully altered.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Dióxido de Carbono/sangue , Circulação Cerebrovascular/fisiologia , Oximetria/métodos , Oxigênio/sangue , Adulto , Feminino , Humanos , Masculino , Pressão Parcial , Artéria Radial/metabolismo , Adulto JovemRESUMO
Vascular calcification (VC) is a very common phenomenon in patients with chronic kidney disease(CKD) and it increases the incidence of cardiovascular disease and leads to high mortality in CKD patients. It has been reported that some microRNAs (miRs) play roles in vascular calcification as an epigenetic regulator. Indoxyl sulfate (IS) is a protein-bound uremic toxin which has been proven as one of the major risk factors of cardiovascular disease in CKD. Here we investigated whether microRNA-29b (miR-29b) is involved in IS-induced vascular calcification. We found that vascular miR-29b was down-regulated in radial arteries of patients with end-stage renal disease. Consistently, IS also decreased miR-29b expression in human aortic smooth muscle cells (HASMCs) and potentiated their calcification. MiR-29b mimics significantly suppressed, while miR-29b anti-miR markedly enhanced, IS-induced runt-related transcription factor 2 and osteopontin expression. The expression of Wnt7b/ß-catenin in radial arteries was higher in end stage renal disease than in control group, and IS increased Wnt7b/ß-catenin expression in HASMCs as early as 3days after stimulation. Furthermore, miR-29b mimics potently repressed Wnt7b/ß-catenin protein expression in HASMCs, whereas miR-29b anti-miR increased their expression, indicating miR-29b indeed negatively regulates Wnt7b/ß-catenin signaling. Dickkopf-1 protein, the Wnt/ß-catenin signaling inhibitor, suppressed anti-miR-29b-enhanced HASMCs calcification. Our data thus indicate that miR-29b downregulation and Wnt/ß-catenin signaling activation may be the key mechanism of IS induced vascular calcification in chronic kidney disease.
Assuntos
Indicã/toxicidade , Falência Renal Crônica/metabolismo , MicroRNAs/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Calcificação Vascular/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Técnicas de Cultura de Células , Células Cultivadas , Regulação para Baixo , Humanos , Indicã/metabolismo , MicroRNAs/genética , Músculo Liso Vascular/metabolismo , Artéria Radial/efeitos dos fármacos , Artéria Radial/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Transradial catheterization is associated with radial artery injury and vasomotor dysfunction and represents an accessible model of acute vascular injury in humans. We characterized vascular injury and functional recovery to understand the role of circulating endothelial progenitor cells in vascular repair. METHODS AND RESULTS: In 50 patients (aged 64±10 years, 70% male) undergoing transradial cardiac catheterization, radial artery injury was assessed by optical coherence tomography and examination of explanted vascular sheaths. Flow- and nitrate-mediated dilatation of the radial artery was assessed in both arms at baseline, at 24 hours, and at 1, 4, and 12 weeks. Circulating endothelial progenitor cell populations were quantified using flow cytometry. Late endothelial outgrowth colonies were isolated and examined in vitro. Optical coherence tomography identified macroscopic injury in 12 of 50 patients (24%), but endothelial cells (1.9±1.2×104 cells) were isolated from all arterial sheaths examined. Compared with the noncatheterized radial artery, flow-mediated vasodilatation was impaired in the catheterized artery at 24 hours (9.9±4.6% versus 4.1±3.1%, P<0.0001) and recovered by 12 weeks (8.1±4.9% versus 10.1±4.9%, P=0.09). Although the number of CD133+ cells increased 24 hours after catheterization (P=0.02), the numbers of CD34+ cells and endothelial outgrowth colonies were unchanged. Migration of endothelial cells derived from endothelial outgrowth colonies correlated with arterial function before catheterization but was not related to recovery of function following injury. CONCLUSIONS: Transradial cardiac catheterization causes endothelial denudation, vascular injury, and vasomotor dysfunction that recover over 12 weeks. Recovery of vascular function does not appear to be dependent on the mobilization or function of endothelial progenitor cells. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147119.
Assuntos
Cateterismo Cardíaco/efeitos adversos , Cateterismo Periférico/efeitos adversos , Movimento Celular , Proliferação de Células , Células Progenitoras Endoteliais/patologia , Artéria Radial/patologia , Lesões do Sistema Vascular/patologia , Antígeno AC133/sangue , Idoso , Antígenos CD34/sangue , Cateterismo Cardíaco/métodos , Cateterismo Periférico/métodos , Separação Celular/métodos , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Punções , Artéria Radial/lesões , Artéria Radial/metabolismo , Artéria Radial/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Tomografia de Coerência Óptica , Ultrassonografia , Lesões do Sistema Vascular/sangue , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/fisiopatologia , VasodilataçãoRESUMO
Reperfusion in the setting of acute ischemia is essential in limiting tissue necrosis. However, reperfusion itself is associated with significant adverse effects. There is animal evidence that platelets play a role in the adverse effects of ischemia and reperfusion (IR) injury. We examined whether clopidogrel would have favorable effects on endothelial dysfunction induced by an episode of IR. Using a parallel design, we administered clopidogrel 600 mg or matching placebo to normal volunteers (n = 20) 24 hours before an episode of IR. Flow-mediated dilatation (FMD, radial artery) was assessed before and after 20 minutes of upper arm ischemia. Following IR, there was a highly significant decrease in FMD in the placebo group (7.6% ± 1.3% vs 3.4% ± 0.1%; P < .001). In the clopidogrel group, there was no change in FMD post-IR (8.3% ± 0.8% vs 7.1% ± 1.2%; P = not significant). Following IR, FMD in the placebo group was significantly smaller than that observed in the clopidogrel group ( P < .01). Ischemia and reperfusion caused no change in plasma levels of biomarkers of inflammation (intercellular adhesion molecule 1, chemokine ligand 5, and interleukin 6) in either group. Therefore, a single dose of clopidogrel given 24 hours prior to an episode of IR had protective effects, limiting the adverse effects of ischemia on endothelial function.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Artéria Radial/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Ticlopidina/análogos & derivados , Extremidade Superior/irrigação sanguínea , Adolescente , Adulto , Biomarcadores/sangue , Quimiocina CCL5/sangue , Clopidogrel , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Voluntários Saudáveis , Humanos , Mediadores da Inflamação/sangue , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Masculino , Inibidores da Agregação Plaquetária/efeitos adversos , Artéria Radial/diagnóstico por imagem , Artéria Radial/metabolismo , Artéria Radial/fisiopatologia , Fluxo Sanguíneo Regional , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/etiologia , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Fatores de Tempo , Ultrassonografia Doppler , Vasodilatação/efeitos dos fármacos , Adulto JovemRESUMO
PURPOSE: Bone metabolism disorder is often associated with cardiovascular calcification in patients with chronic kidney disease (CKD). Sclerostin, a novel candidate protein, has been identified to be involved in the bone-vascular axis. The aims of the current investigation were to assess vessel sclerostin expression and its relationship with circulating sclerostin levels. METHODS: A cross-sectional observational study was conducted from January 2012 to December 2014. Thirty-two predialysis patients with CKD stage 5 who received arteriovenous fistula (AVF) operations were enrolled in this study. Radial arteries were collected and paraffin-embedded during the AVF operation, followed by immunohistochemical staining for sclerostin expression. In addition, serum sclerostin levels were measured by the enzyme-linked immunosorbent assay. RESULTS: The prevalence of positive sclerostin staining in the radial arteries was 56.25%. Sclerostin expression was localized in the artery media layer. Serum sclerostin levels in patients with positive sclerostin expression were much higher than in those with negative expression (p = 0.018). Multivariate logistic regression analyses including potential confounders as age, gender, systolic blood pressure (BP), diastolic BP, serum sclerostin, corrected calcium (Ca), phosphate (P), Ca × P product, alkaline phosphatase, intact parathyroid hormone, and estimated glomerular filtration rate showed that only serum sclerostin levels were closely related to vessel sclerostin expression (p = 0.025). The area under the curve of serum sclerostin levels for predicting positive vessel sclerostin expression was 0.742 with 61.1% sensitivity and 85.7% specificity (p = 0.008). The cutoff point for vessel sclerostin expression of serum sclerostin was 1591.53 pg/mL. CONCLUSIONS: Positive expression of sclerostin in the radial artery media layer was related to high serum sclerostin levels. Sclerostin may act as both a local and systemic regulator involved in vascular calcification.
Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Falência Renal Crônica/sangue , Artéria Radial/metabolismo , Túnica Média/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Área Sob a Curva , Proteínas Morfogenéticas Ósseas/sangue , Estudos Transversais , Feminino , Marcadores Genéticos , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Curva ROC , Diálise RenalRESUMO
BACKGROUND: Endothelin receptor antagonists are approved for pulmonary arterial hypertension. Development of selective ETA-receptor antagonists over mixed or dual receptor antagonists has depended on a range of receptor binding assays, second messenger assays and functional blood vessel assays. This study compared the 3 clinically-approved endothelin receptor antagonists in assays of human isolated pulmonary and radial arteries in vitro. METHODS: Human isolated pulmonary (i.d. 5.5mm) and human radial (i.d. 3.23mm) artery ring segments were mounted in organ baths for isometric force measurement. Single concentration-contraction curves to endothelin-1 were constructed in the absence or presence of bosentan (1-10µM), macitentan (0.03-0.3µM) or ambrisentan (0.1-1µM). RESULTS: All 3 endothelin antagonists caused competitive rightward shifts in the endothelin-1 concentration-response curves in both arteries. The Clark plot and analysis gave the following pKB values: bosentan, pulmonary artery 6.28±0.13 and radial artery 6.04±0.10; macitentan, pulmonary artery 8.02±0.13 and radial artery 7.49±0.08; and ambrisentan, pulmonary artery 7.38±0.13 and radial artery 6.96±0.10. CONCLUSIONS: Noting the maximum plasma levels attained from recommended oral doses of each antagonist in volunteers, the pKB findings here show that there would be significant antagonism of endothelin-1 contraction in the pulmonary and radial arteries at therapeutic plasma levels. This functional assay confirms in human tissue that much higher plasma concentrations of endothelin-1 receptor antagonists are required to be effective than those predicted from binding or other biochemical assays.
Assuntos
Antagonistas dos Receptores de Endotelina/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Artéria Radial/efeitos dos fármacos , Artéria Radial/fisiopatologia , Receptor de Endotelina A/metabolismo , Bosentana , Relação Dose-Resposta a Droga , Antagonistas dos Receptores de Endotelina/uso terapêutico , Endotelina-1/metabolismo , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Fenilpropionatos/farmacologia , Fenilpropionatos/uso terapêutico , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Piridazinas/farmacologia , Piridazinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Artéria Radial/metabolismo , Artéria Radial/patologia , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Sobrevivência de Tecidos/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacosRESUMO
Plasma levels of several amino acids are correlated with metabolic dysregulation in obesity and type 2 diabetes. To increase our understanding of human amino-acid metabolism, we aimed to determine splanchnic interorgan amino-acid handling. Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy were included in this study. Blood was sampled from the portal vein, hepatic vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal vein, and the radial artery during surgery. The difference between arterial and venous concentrations of 21 amino acids was determined using liquid chromatography as a measure of amino-acid metabolism across a given organ. Whereas glutamine was significantly taken up by the small intestine (121.0 ± 23.8 µmol/L; P < 0.0001), citrulline was released (-36.1 ± 4.6 µmol/L; P < 0.0001). This, however, was not seen for the colon. Interestingly, the liver showed a small, but a significant uptake of citrulline from the circulation (4.8 ± 1.6 µmol/L; P = 0.0138) next to many other amino acids. The kidneys showed a marked release of serine and alanine into the circulation (-58.0 ± 4.4 µmol/L and -61.8 ± 5.2 µmol/L, P < 0.0001), and a smaller, but statistically significant release of tyrosine (-12.0 ± 1.3 µmol/L, P < 0.0001). The spleen only released taurine (-9.6 ± 3.3 µmol/L; P = 0.0078). Simultaneous blood sampling in different veins provides unique qualitative and quantitative information on integrative amino-acid physiology, and reveals that the well-known intestinal glutamine-citrulline pathway appears to be functional in the small intestine but not in the colon.
Assuntos
Aminoácidos/sangue , Neoplasias Duodenais/metabolismo , Neoplasias Pancreáticas/metabolismo , Pancreaticoduodenectomia/métodos , Circulação Esplâncnica/fisiologia , Idoso , Colo/irrigação sanguínea , Colo/metabolismo , Neoplasias Duodenais/irrigação sanguínea , Neoplasias Duodenais/cirurgia , Feminino , Veias Hepáticas/metabolismo , Humanos , Intestino Delgado/irrigação sanguínea , Intestino Delgado/metabolismo , Rim/irrigação sanguínea , Rim/metabolismo , Fígado/irrigação sanguínea , Fígado/metabolismo , Masculino , Veias Mesentéricas/metabolismo , Pessoa de Meia-Idade , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/cirurgia , Veia Porta/metabolismo , Artéria Radial/metabolismo , Veias Renais/metabolismo , Baço/irrigação sanguínea , Baço/metabolismo , Veia Esplênica/metabolismoRESUMO
AIM: To determine whether acute loss of liver tissue affects hepatic short-chain fatty acid (SCFA) clearance. METHODS: Blood was sampled from the radial artery, portal vein, and hepatic vein before and after hepatic resection in 30 patients undergoing partial liver resection. Plasma SCFA levels were measured by liquid chromatography-mass spectrometry. SCFA exchange across gut and liver was calculated from arteriovenous differences and plasma flow. Liver volume was estimated by CT liver volumetry. RESULTS: The gut produced significant amounts of acetate, propionate, and butyrate (39.4±13.5, 6.2±1.3, and 9.5±2.6 µmol·kgbw-1·h-1), which did not change after partial hepatectomy (p = 0.67, p = 0.59 and p = 0.24). Hepatic propionate uptake did not differ significantly before and after resection (-6.4±1.4 vs. -8.4±1.5 µmol·kgbw-1·h-1, p = 0.49). Hepatic acetate and butyrate uptake increased significantly upon partial liver resection (acetate: -35.1±13.0 vs. -39.6±9.4 µmol·kgbw-1·h-1, p = 0.0011; butyrate: -9.9±2.7 vs. -11.5±2.4 µmol·kgbw-1·h-1, p = 0.0006). Arterial SCFA concentrations were not different before and after partial liver resection (acetate: 176.9±17.3 vs. 142.3±12.5 µmol/L, p = 0.18; propionate: 7.2±1.4 vs. 5.6±0.6 µmol/L, p = 0.38; butyrate: 4.3±0.7 vs. 3.6±0.6 µmol/L, p = 0.73). CONCLUSION: The liver maintains its capacity to clear acetate, propionate, and butyrate from the portal blood upon acute loss of liver tissue.
Assuntos
Ácidos Graxos Voláteis/metabolismo , Hepatectomia/métodos , Fígado/metabolismo , Fígado/cirurgia , Acetatos/metabolismo , Adulto , Idoso , Ácido Butírico/metabolismo , Ácidos Graxos Voláteis/sangue , Feminino , Veias Hepáticas/metabolismo , Humanos , Fígado/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Veia Porta/metabolismo , Período Pós-Operatório , Período Pré-Operatório , Propionatos , Artéria Radial/metabolismoRESUMO
Vascular calcification (VC) is an independent risk factor for cardiovascular disease and mortality in uremia. Post-translational core fucosylation is implicated in a number of pathological processes. First, we investigated the role of core fucosylation and key TGF-ß1 pathway receptors in calcified arteries in vivo. To determine whether blocking core fucosylation effectively inhibited VC and TGF-ß/Smad signaling pathway, we established an in vitro model of phosphate-induced calcification in rat vascular smooth muscle cells (VSMCs) to assess the role of core fucosylation in VC. Core fucose could be detected at markedly higher levels in calcified VSMCs than control cells. Fut8 (α-1,6 fucosyltransferase), the only enzyme responsible for core fucosylation in humans, was significantly upregulated by high phosphate. Exposed to high phosphate media and blocking core fucosylation in VSMCs by knocking down Fut8 using a siRNA markedly reduced calcium and phosphorus deposition and Cbfα1 expression (osteoblast-specific transcription factor), and increased α-Sma expression (smooth muscle cell marker). Fut8 siRNA significantly inhibited TGF-ß/Smad2/3 signaling activation in VSMCs cultured in high phosphate media. In conclusion, this study provides evidence to suggest core fucosylation plays a major role in the process of VC and appropriate blockade of core fucosylation may represent a potential therapeutic strategy for treating VC in end-stage renal disease.