RESUMO
OBJECTIVE: To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls. STUDY DESIGN: Patients with OSA and matched controls (ages 5-13 years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures. RESULTS: Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P < .05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P < .05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P < .05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P < .05 for each). Children with OSA did not have functional or structural carotid changes compared with controls. CONCLUSION: OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.
Assuntos
Proteínas de Fase Aguda/metabolismo , Aterosclerose/etiologia , Artéria Carótida Primitiva/fisiopatologia , Citocinas/sangue , Inflamação/etiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adolescente , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/fisiopatologia , Modelos Lineares , Masculino , Estudos Prospectivos , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , UltrassonografiaRESUMO
BACKGROUND: Although conventional angiography remains the reference standard for the grading of carotid stenosis, carotid duplex ultrasound (CDUS) is the most commonly used modality for determining the degree of carotid stenosis. The validity of CDUS findings for patients after left ventricular assist device (LVAD) implantation is questionable, because the velocities are often altered secondary to the continuous flow nature of the devices. METHODS: A retrospective review was performed of all patients who had undergone LVAD implantation from January 2007 to December 2019. All patients who had undergone CDUS before and after LVAD implantation were included. Patients receiving extracorporeal membrane oxygenation, those with unusable carotid imaging studies, and those with internal carotid artery (ICA) occlusion were excluded. The peak systolic velocity (PSV) and end-diastolic velocity (EDV) in the ICA and common carotid artery (CCA) and the ICA/CCA ratios were compared before and after LVAD implantation. RESULTS: A total of 36 patients (mean age 59 years; 30 men; 6 women) had undergone CDUS both before and after LVAD implantation (mean, 647 days between imaging studies). A total of 61 ICAs had met the criteria for inclusion. Before LVAD, 7 carotid arteries (13%) had had >50% carotid stenosis and 53 (87%) had had 0% to 50% stenosis. The mean changes in the velocities after LVAD were as follows. The ICA PSV had decreased by 6.12 ± 4.34 cm/s, and the ICA EDV had increased by 13.44 ± 4.23 cm/s. The CCA PSV had decreased by 17.22 ± 4.95 cm/s, and the CCA EDV had increased by 10.83 ± 2.59 cm/s. The mean ICA/CCA ratio had increased by 0.18 ± 0.05. All the mean changes in velocity were significant (P < .01), except for the ICA PSV (P = .167). Among four patients with known stenosis of 60% to 69%, the degree of increase in the ICA and CCA EDVs (75.8 and 13.3 cm/s, respectively) was significantly greater than that for patients with <50% or no stenosis. Carotid artery laterality did not significantly affect the differences in mean velocity. Centrifugal LVADs resulted in a significantly larger increase in the ICA EDV compared with axial LVADs (26.0 vs 6.3 cm/s; P < .01). CONCLUSIONS: LVADs were associated with significant changes in CCA PSV, ICA and CCA EDV, and ICA/CCA ratios. However, the magnitude of these changes in patients with <50% stenosis was minimal and might not be clinically significant. The LVAD type might only have an effect on EDV measurements in the CCA, and the left and right carotid arteries did not appear to have different degrees of change in velocity. The currently used criteria for determining carotid stenosis might result in an under- or overestimation of carotid stenosis in patients with an LVAD.
Assuntos
Artéria Carótida Primitiva/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Coração Auxiliar , Ultrassonografia Doppler Dupla , Função Ventricular Esquerda , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Artéria Carótida Primitiva/fisiopatologia , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/fisiopatologia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Endothelial dysfunction is observed in the peripheral vasculature of hypertensive patients, but it is unclear how the cerebral circulation is affected. More specifically, little is known about the impact of human hypertension on vertebral artery (VA) endothelial function. This study evaluated whether the endothelial function of the VA is impaired in hypertensive men. For 13 male hypertensive subjects (46 ± 3 yr) and eight age-matched male controls (46 ± 4 yr), blood pressure (BP; photoplethysmography), VA, and common carotid (CC) blood flow (duplex ultrasound) were determined at rest and during 30 min of intravenous l-arginine (30 g; a precursor of nitric oxide) or isotonic saline infusion. Controls and hypertensive subjects demonstrated a similar resting CC (601 ± 30 vs. controls 570 ± 43 ml/min; P = 0.529) and VA blood flow (119 ± 11 vs. controls 112 ± 9 ml/min; P = 0.878). During administration of l-arginine, CC blood flow increased similarly between groups (hypertensive 12 ± 3%, controls 13 ± 2%; P = 0.920). In contrast, the increase in VA blood flow was nonexistent in the hypertensive subjects (0.8 ± 3% vs. controls: 16 ± 4%; P = 0.015) with no significant change in BP. Both CC and VA flow returned to near-resting values within 30 min after the infusion, and for four hypertensive subjects and three controls, time-control experiments using 0.9% saline did not affect VA or CC blood flow significantly. The results demonstrate endothelial dysfunction in the posterior cerebral circulation of middle-aged hypertensive men.
Assuntos
Arginina/administração & dosagem , Circulação Cerebrovascular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Hipertensão/fisiopatologia , Artéria Vertebral/efeitos dos fármacos , Adulto , Velocidade do Fluxo Sanguíneo , Artéria Carótida Primitiva/efeitos dos fármacos , Artéria Carótida Primitiva/fisiopatologia , Estudos de Casos e Controles , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão/diagnóstico , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Fatores de Tempo , Artéria Vertebral/fisiopatologiaRESUMO
The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.
O presente estudo teve como objetivo investigar alterações comportamentais e processos inflamatórios na isquemia cerebral induzida pela oclusão unilateral da carótida comum esquerda (UCCAO) em camundongos. As alterações comportamentais foram avaliadas após 15 minutos de isquemia e 24 horas de reperfusão. O teste de reconhecimento de objetos foi utilizado para avaliação da memória e do aprendizado. Em seguida, os animais foram mortos e os encéfalos foram coletados e processados para avaliação das alterações patológicas pelas técnicas de TTC e H&E, assim como da dosagem de mediadores inflamatórios por ELISA. A UCCAO promoveu alterações de memória após a reperfusão. Foram visualizadas áreas de infarto cerebral pela coloração de TTC e cavidades necróticas circundadas por neurônios isquêmicos no cérebro e neurodegeneração hipocampal. A UCCAO causou aumento dos níveis encefálicos de TNF-a, IL-1b e CXCL1. Estes achados demonstraram o envolvimento dos mediadores inflamatórios no sistema nervoso central e da neurodegeneração no déficit cognitivo após isquemia cerebral aguda.
Assuntos
Animais , Masculino , Encéfalo/patologia , Citocinas/análise , Transtornos da Memória/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Encéfalo/irrigação sanguínea , Artéria Carótida Primitiva/fisiopatologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Doenças Neurodegenerativas/fisiopatologia , Neurônios/patologia , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/fisiopatologia , Acidente Vascular Cerebral/complicações , Fatores de TempoRESUMO
The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These ï¬ndings suggest an involvement of central nervous system inï¬ammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.
Assuntos
Encéfalo/patologia , Citocinas/análise , Transtornos da Memória/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Encéfalo/irrigação sanguínea , Artéria Carótida Primitiva/fisiopatologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Masculino , Transtornos da Memória/etiologia , Camundongos Endogâmicos C57BL , Doenças Neurodegenerativas/fisiopatologia , Neurônios/patologia , Testes Neuropsicológicos , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/fisiopatologia , Acidente Vascular Cerebral/complicações , Fatores de TempoRESUMO
CONTEXT AND OBJECTIVE: The thickness of the carotid intima-media complex (C-IMC) is considered to be a marker of early atherosclerosis, but visual and echogenic changes to the C-IMC can also be noted. The objective here was to evaluate the relationship between cardiovascular risk factors and the echogenicity of the C-IMC and identify those most associated with an "abnormal" C-IMC. DESIGN AND SETTING: Cross-sectional study in the ultrasound sector of the Department of Diagnostic Imaging, Universidade Federal de São Paulo. METHODS: Eighty men were evaluated. Measurements of arterial blood pressure, waist circumference (WC), lipid profile, fasting glucose, uric acid and high-sensitivity C-reactive protein were obtained. The thickness of the C-IMC was measured by means of B-mode ultrasound, and the intima-media gray-scale mean (IM-GSM) and standard deviation (IM-SD) were calculated. RESULTS: The following were discriminating variables: fasting glucose (r2 = 0.036; P = 0.013), uric acid (r2 = 0.08; P = 0.03), IM-SD (r2 = 0.43; P < 0.001), IM-GSM (r2 = 0.35; P < 0.001) and thickness of the C-IMC (r2 = 0.29; P < 0.001). IM-GSM showed significant correlations with WC (r = -0.22; P = 0.005), fasting glucose (r = -0.24; P = 0.002) and high-density lipoprotein cholesterol (HDL-C) (r = 0.27; P = 0.0007). CONCLUSION: IM-GSM showed correlations with WC, fasting glucose and HDL-C. However, uric acid and IM-SD presented the greatest discriminating impact. These results suggest that visual changes in C-IMC may help identify patients with potential cardiovascular risk, independently of the thickness of the C-IMC.
Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Síndrome Metabólica/diagnóstico por imagem , Adulto , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Proteína C-Reativa/análise , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Artéria Carótida Primitiva/fisiopatologia , Estudos Transversais , Jejum/sangue , Glucose/metabolismo , Humanos , Lipoproteínas HDL/sangue , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Valores de Referência , Medição de Risco , Fatores de Risco , Ácido Úrico/sangue , Circunferência da CinturaRESUMO
CONTEXT AND OBJECTIVE: The thickness of the carotid intima-media complex (C-IMC) is considered to be a marker of early atherosclerosis, but visual and echogenic changes to the C-IMC can also be noted. The objective here was to evaluate the relationship between cardiovascular risk factors and the echogenicity of the C-IMC and identify those most associated with an "abnormal" C-IMC. DESIGN AND SETTING: Cross-sectional study in the ultrasound sector of the Department of Diagnostic Imaging, Universidade Federal de São Paulo. METHODS: Eighty men were evaluated. Measurements of arterial blood pressure, waist circumference (WC), lipid profile, fasting glucose, uric acid and high-sensitivity C-reactive protein were obtained. The thickness of the C-IMC was measured by means of B-mode ultrasound, and the intima-media gray-scale mean (IM-GSM) and standard deviation (IM-SD) were calculated. RESULTS: The following were discriminating variables: fasting glucose (r2 = 0.036; P = 0.013), uric acid (r2 = 0.08; P = 0.03), IM-SD (r2 = 0.43; P < 0.001), IM-GSM (r2 = 0.35; P < 0.001) and thickness of the C-IMC (r2 = 0.29; P < 0.001). IM-GSM showed significant correlations with WC (r = -0.22; P = 0.005), fasting glucose (r = -0.24; P = 0.002) and high-density lipoprotein cholesterol (HDL-C) (r = 0.27; P = 0.0007). CONCLUSION: IM-GSM showed correlations with WC, fasting glucose and HDL-C. However, uric acid and IM-SD presented the greatest discriminating impact. These results suggest that visual changes in C-IMC may help identify patients with potential cardiovascular risk, independently of the thickness of the C-IMC. .
CONTEXTO E OBJETIVO: A espessura do complexo íntima-média carotídeo (CIM-C) é considerada um marcador da aterosclerose precoce, mas alterações visuais e da ecogenicidade do CIM-C também podem ser observadas. O objetivo foi avaliar a relação entre os fatores de risco cardiovascular e a ecogenicidade do CIM-C e identificar aqueles mais relacionados com o CIM-C "alterado". TIPO DE ESTUDO E LOCAL: Estudo transversal no setor de ultrassonografia do Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo. MÉTODOS: Oitenta homens foram avaliados. Aferição da pressão arterial, medida da circunferência abdominal (CA), perfil lipídico, glicemia de jejum (GLI), ácido úrico (AU) e proteína C-reativa de alta sensibilidade foram obtidos. A espessura do CIM-C foi medida por ultrassom modo B e a média da escala de cinza (GSM) e do desvio padrão do CIM (DPIM) foram calculados. RESULTADOS: As variáveis discriminantes foram GLI (r2 = 0,036; P = 0,013), AU (r2 = 0,08; P = 0,03), DPIM (r2 = 0,43; P < 0,001), GSM (r2 = 0,35; P < 0,001) e espessura do CIM-C (r2 = 0.29; P < 0,001). Houve correlação significativa entre GSM e CA (r = -0,22; P = 0,005), GLI (r = -0,24; P = 0,002) e lipoproteína de alta densidade do colesterol (HDL-C) (r = 0,27; P = 0,0007). CONCLUSÃO: A GSM teve correlação com CA, GLI, HDL-C. Entretanto, AU e DPIM apresentaram maior impacto discriminante, sugerindo que alterações visuais do CIM-C, independentemente da espessura, podem auxiliar na identificação de pacientes com potencial risco cardiovascular. .
Assuntos
Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares , Artéria Carótida Primitiva , Espessura Intima-Media Carotídea , Síndrome Metabólica , Aterosclerose/fisiopatologia , Aterosclerose , Proteína C-Reativa/análise , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Artéria Carótida Primitiva/fisiopatologia , Estudos Transversais , Jejum/sangue , Glucose/metabolismo , Lipoproteínas HDL/sangue , Síndrome Metabólica/fisiopatologia , Valores de Referência , Medição de Risco , Fatores de Risco , Ácido Úrico/sangue , Circunferência da CinturaRESUMO
The present study examined the behavioral and neurohistological changes induced by the bilateral common carotid artery occlusion (BCCAO) model of brain ischemia in Swiss mice. The post-ischemic behavioral effects of 17min BCCAO were recorded 7, 14, and 28 days after reperfusion in the Morris water maze, open field, and elevated plus maze to assess spatial learning and memory, general locomotor activity, and levels of anxiety-like behavior, respectively. After behavioral testing, the brains were removed and processed to evaluate hippocampal neurodegeneration using Nissl staining and Fluoro-Jade C histochemistry and hippocampal neurogenesis using doublecortin immunohistochemistry. BCCAO induced memory impairment 7 and 14 days after reperfusion, with apparent functional recovery 28 days later. Anxiety-related behaviors remained elevated in ischemic compared to sham mice tested 28 days after reperfusion. Hippocampal neurodegeneration was detected in all hippocampal subfields (CA1-CA4) from day 7 to day 28. Decreased hippocampal neurogenesis was observed 14 and 28 days after BCCAO. The effects of BCCAO on spatial memory were transient, whereas anxiety-like behavior was persistent and might be related to CA3 hippocampal injury induced by BCCAO in mice.
Assuntos
Ansiedade/etiologia , Comportamento Animal/fisiologia , Isquemia Encefálica/complicações , Artéria Carótida Primitiva/fisiopatologia , Estenose das Carótidas/complicações , Transtornos Cognitivos/etiologia , Animais , Ansiedade/patologia , Ansiedade/fisiopatologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Estenose das Carótidas/patologia , Estenose das Carótidas/fisiopatologia , Contagem de Células , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Neurogênese/fisiologia , Neurônios/patologia , Neurônios/fisiologiaRESUMO
PURPOSE: To evaluate the effect of cerebral hypoxia-ischemia on memory and learning survival of rats submitted to permanent bilateral carotid ligation (PBCL). METHODS: Twenty-four survivors of PBCL were evaluated after 30 days with regard to memory and learning using a water survival maze. Twenty-three healthy rats were used as control group. The results were expressed by their means and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee for animal investigation. RESULTS: The mortality rate for the surgery was 44.4%. The latency time to find the survival platform was higher in rats that underwent PBCL (Normal: 10.24 ± 1.85s - STUDY: 25.30 ± 4.69s - Mann - Whitney p=0.0388). Additionally, the type of swimming and the spatial stability of the studied rats on the survival platform were compromised in these animals. CONCLUSION: The permanent bilateral carotid ligation induces change in the learning and survival memory.
Assuntos
Arteriopatias Oclusivas/fisiopatologia , Artéria Carótida Primitiva/fisiopatologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Aprendizagem/fisiologia , Memória/fisiologia , Animais , Encéfalo/irrigação sanguínea , Hipóxia-Isquemia Encefálica/mortalidade , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos WistarRESUMO
PURPOSE: To evaluate the effect of cerebral hypoxia-ischemia on memory and learning survival of rats submitted to permanent bilateral carotid ligation (PBCL). METHODS: Twenty-four survivors of PBCL were evaluated after 30 days with regard to memory and learning using a water survival maze. Twenty-three healthy rats were used as control group. The results were expressed by their means and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee for animal investigation. RESULTS: The mortality rate for the surgery was 44.4%. The latency time to find the survival platform was higher in rats that underwent PBCL (Normal: 10.24 ± 1.85s - Study: 25.30 ± 4.69s - Mann - Whitney p=0.0388). Additionally, the type of swimming and the spatial stability of the studied rats on the survival platform were compromised in these animals. CONCLUSION: The permanent bilateral carotid ligation induces change in the learning and survival memory.