Aberrant right subclavian artery: case report and literature review.

The aberrant right subclavian artery, also known as the arteria lusoria, is the most common aortic arch anomaly, occurring in 0.5 to 1% of the population. There is a higher prevalence in women and it is usually associated with other anatomical variations, such as the non-recurrent laryngeal nerve, present in 86.7% of cases. In the majority of cases, the aberrant right subclavian artery causes no symptoms. We describe this anomaly in an 82-year-old, hypertensive, and asymptomatic patient who had undergone a thoracoabdominal angiography to investigate a chronic DeBakey type III aortic dissection with dilation of the descending aorta. The aberrant right subclavian artery followed a retroesophageal course and was associated with a Kommerell diverticulum. In view of its rarity, we conducted an integrative bibliographic review of literature from the last 6 years indexed on the Medline, UpToDate, Lilacs, Scielo, and Portal Capes databases and discuss the most frequent anatomical changes, symptomatology, and therapeutic management adopted.

Artéria subclávia direita aberrante: relato de caso e revisão de literatura / Aberrant right subclavian artery: case report and literature review

Resumo A artéria subclávia direita aberrante, também conhecida como artéria lusória, é a anomalia do arco aórtico mais comum, ocorrendo entre 0,5 e 1% da população. Possui prevalência em mulheres e normalmente está associada a outras variações anatômicas, como o nervo laríngeo não recorrente, presente em 86,7% dos casos. Em sua maioria, a artéria subclávia direita aberrante não apresenta sintomas. Descrevemos essa alteração em uma paciente de 82 anos, hipertensa e assintomática, que havia sido submetida a uma angiotomografia toracoabdominal para a avaliação de uma dissecção crônica tipo III (DeBakey) associada à dilatação de aorta descendente. No achado, a artéria subclávia direita aberrante apresentava percurso retroesofágico associado a um divertículo de Kommerell. Devido à raridade, realizamos revisão bibliográfica integrativa das bases de dados MEDLINE, UpToDate, LILACS, SciELO e Portal CAPES dos últimos 6 anos e discutimos as alterações anatômicas mais frequentes, a sintomatologia e as condutas terapêuticas adotadas.

Abstract The aberrant right subclavian artery, also known as the arteria lusoria, is the most common aortic arch anomaly, occurring in 0.5 to 1% of the population. There is a higher prevalence in women and it is usually associated with other anatomical variations, such as the non-recurrent laryngeal nerve, present in 86.7% of cases. In the majority of cases, the aberrant right subclavian artery causes no symptoms. We describe this anomaly in an 82-year-old, hypertensive, and asymptomatic patient who had undergone a thoracoabdominal angiography to investigate a chronic DeBakey type III aortic dissection with dilation of the descending aorta. The aberrant right subclavian artery followed a retroesophageal course and was associated with a Kommerell diverticulum. In view of its rarity, we conducted an integrative bibliographic review of literature from the last 6 years indexed on the Medline, UpToDate, Lilacs, Scielo, and Portal Capes databases and discuss the most frequent anatomical changes, symptomatology, and therapeutic management adopted.

Internal carotid artery dissection in a patient with Ehlers-Danlos syndrome type IV: diagnosis and management / Disseccção da artéria carótida interna em paciente com síndrome de Ehlers-Danlos tipo IV: diagnóstico e manejo

Ehlers-Danlos syndrome (EDS) type IV, also known as vascular EDS, is an inherited connective tissue disorder with an estimated prevalence of 1/100,000 to 1/250,000. In EDS type IV, vascular complications may affect all anatomical areas, with a preference for large- and medium-sized arteries. Dissections of the vertebral and carotid arteries in their extra- and intra-cranial segments are typical. The authors report the case of a patient with EDS type IV for whom the diagnosis was established based on clinical signs and who developed internal carotid artery dissection at the age of 44 years. In the absence of a specific treatment for EDS type IV, medical interventions should focus on symptomatic relief, prophylactic measures, and genetic counseling. Invasive imaging techniques are contraindicated, and a conservative approach to vascular complications is usually recommended.

A síndrome de Ehlers-Danlos (EDS) tipo IV, também conhecida como EDS tipo vascular, é uma doença genética do tecido conjuntivo com prevalência estimada entre 1/100.000 e 1/250.000. Na EDS tipo IV, as complicações vasculares podem afetar todas as áreas anatômicas, com comprometimento preferencial de artérias de médio e grande diâmetros. Dissecções das artérias vertebrais e carótidas em seus segmentos intra e extracranianos são típicas. Os autores relatam o caso de uma paciente com EDS tipo IV na qual o diagnóstico sindrômico foi realizado com base nos achados clínicos e que desenvolveu dissecção da artéria carótida interna aos 44 anos. Na ausência de um tratamento específico para EDS tipo IV, a intervenção médica deve ser voltada para o tratamento sintomático, para medidas profiláticas e para o aconselhamento genético. Técnicas de imagem invasivas são contraindicadas e, geralmente, recomenda-se uma abordagem conservadora ao cuidar das complicações vasculares.

Isquemia crítica em membro inferior em paciente jovem com doença cística de artéria poplítea / Critical limb ischemia in a young patient with cystic disease of the popliteal artery

Degeneração cística da artéria poplítea é uma doença vascular rara, de etiologia desconhecida, na qual um cisto com conteúdo mucinoide compromete a artéria e desenvolve estenose ou oclusão do vaso. Apresentamos um caso de um paciente do sexo masculino, 45 anos, admitido na emergência hospitalar, que apresentava quadro de isquemia aguda no membro inferior esquerdo. Submetido à EcoDoppler, angiorressonância magnética e angiografia pré-operatória. Realizada arterectomia com enxerto fêmoro-poplíteo infrainguinal de safena invertida. O exame patológico foi consistente com o diagnóstico de doença cística da artéria poplítea. O paciente encontra-se em acompanhamento ambulatorial e foi acometido pela doença cística no membro contralateral. Os autores descreveram os melhores métodos de diagnóstico e tratamento para a doença, discutindo se o procedimento de urgência foi o mais adequado e se haveria opções terapêuticas alternativas para o caso, além de qual seria a melhor conduta a ser realizada no membro contralateral também acometido pela doença.

Cystic adventitial disease of the popliteal artery is a rare vascular disease of unknown etiology in which a mucin-containing cyst may compromise the artery and, because of the compression, develops stenosis or occlusion of affected artery. We report the case of a 45-year-old male with cystic adventitial disease of the left popliteal artery, after admission for an acute limb ischemia in his left leg, diagnosed non-invasively with EcoDoppler vascular dual scan, magnetic resonance angiography, angiography. Performed complete removal of the cyst with arteriectomy and venous replacement. The pathologic result ware consistent with the diagnostic of cystic adventitial disease. The patient is in ambulatory follow up and was affected by cystic disease in the contralateral limb. The authors described the best methods of diagnosis and treatment for cystic adventitial disease, discussing if the urgency procedure was the most appropriate and whether there was an alternative treatment for the case. Finally, questioning what would be the best procedure to be performed in the other limb.

Oxidized low-density lipoprotein and ankle-brachial pressure index in patients with clinically evident peripheral arterial disease.

OBJECTIVES: To investigate whether oxidized low-density lipoprotein is a suitable predictor of peripheral arterial disease severity. The role of oxidized low-density lipoprotein in the pathogenesis of atherosclerosis has already been investigated. Its relevance as a predictor of the appearance and worsening of coronary arterial disease is also well known. However, the same is not true regarding peripheral arterial disease. METHOD: Eighty-five consecutive patients with an ankle-brachial pressure index (ABPI) < 0.9 and the presence of either intermittent claudication or critical lower leg ischemia were included. The plasma level of IgG autoantibodies against oxidized low-density lipoprotein was evaluated through an enzyme-linked immunosorbent assay. The results were categorized into quartiles according to the ankle-brachial pressure index (a marker of peripheral arterial disease severity), and significant differences were investigated with the Kruskal-Wallis test. RESULTS: There was no significant difference between the quartiles for this population (p = 0.33). No correlation was found between the ankle-brachial pressure index and oxidized low-density lipoprotein levels in subjects with clinically evident peripheral arterial disease with a wide range of clinical manifestations. CONCLUSIONS: Oxidized low-density lipoprotein is not a good predictor of peripheral arterial disease severity.

Activated protein C attenuates acute lung injury and apoptosis in a hyperoxic animal model.

Evidence suggests that activated protein C (APC) attenuates acute lung injury (ALI) through antithrombotic and anti-inflammatory mechanisms. The aim of this study was to determine the effects of APC on ALI in adult rats exposed to hyperoxic environment. Rats were divided into control, hyperoxia, hyperoxia + APC, and APC. Hyperoxia and hyperoxia + APC were exposed to 1, 3, and 5 days of hyperoxia. Hyperoxia + APC and APC were injected with APC (5 mg/kg, i.p.) every 12 h. Control and hyperoxia received isotonic sodium chloride solution injection. Measurement of wet to dry ratio and albumin leak demonstrated significant improvement in hyperoxia + APC when compared with hyperoxia. Apoptosis, as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, was significantly reduced in hyperoxia + APC when compared with hyperoxia. Histological evaluation of lung sections showed significant reduction in inflammation, edema, and in the number of marginating neutrophils in hyperoxia + APC as compared with hyperoxia. Transcriptional expression of lung inflammatory mediators demonstrated a time-dependent surge in the levels TNF-alpha, IL-1beta, and IL-6 in response to hyperoxia that was attenuated with APC administration in the presence of hyperoxia. In this rat model, APC attenuates lung injury and the expression of inflammatory mediators in ALI secondary to hyperoxia.

Oxidized low-density lipoprotein and ankle-brachial pressure index in patients with clinically evident peripheral arterial disease

OBJECTIVES: To investigate whether oxidized low-density lipoprotein is a suitable predictor of peripheral arterial disease severity. The role of oxidized low-density lipoprotein in the pathogenesis of atherosclerosis has already been investigated. Its relevance as a predictor of the appearance and worsening of coronary arterial disease is also well known. However, the same is not true regarding peripheral arterial disease. METHOD: Eighty-five consecutive patients with an ankle-brachial pressure index (ABPI) < 0.9 and the presence of either intermittent claudication or critical lower leg ischemia were included. The plasma level of IgG autoantibodies against oxidized low-density lipoprotein was evaluated through an enzyme-linked immunosorbent assay. The results were categorized into quartiles according to the ankle-brachial pressure index (a marker of peripheral arterial disease severity), and significant differences were investigated with the Kruskal-Wallis test. RESULTS: There was no significant difference between the quartiles for this population (p = 0.33). No correlation was found between the ankle-brachial pressure index and oxidized low-density lipoprotein levels in subjects with clinically evident peripheral arterial disease with a wide range of clinical manifestations. CONCLUSIONS: Oxidized low-density lipoprotein is not a good predictor of peripheral arterial disease severity.

Modulation of total ceramide and constituent ceramide species in the acutely and chronically hypoxic mouse heart at different ages.

Ceramide has been implicated in regulatory processes vital for cell survival under different stressors, most notably hypoxia. Little has been done to investigate the contributions of the different ceramide species to the regulation of cell survival. This study aims to highlight the patterns of variation in total ceramide and its species in the growing and hypoxic mouse heart. Mus musculus mice were placed in a hypoxic environment at birth. Control animals remained in room air. The hearts were extracted at different time points: 1 day, 1 week, 4 weeks, and 8 weeks. The total ceramide content and the amounts of component species were assayed by a modified diacylglycerol kinase assay and high-performance liquid chromatography-tandem mass spectroscopy, respectively. Data was collected from both ventricles in hypoxic and control conditions. There was significant polycythemia in the hypoxic versus control animals with a nearly twofold increase in hematocrit levels. Hypoxic right ventricle (RV) mass significantly increased over that of controls at different age groups. When ceramide content was compared in the hypoxic versus control animals, there was a significant increase at day 1 and a significant decrease at week 4 in the left ventricle, whereas a significant decrease was found in the RV at 1 week, 4 weeks, and 8 weeks. There was also a differential involvement of the RV with regard to levels of N-palmitoyl-D-erythro-sphingosine (C16-Cer) and its synthetic precursor dihydro-N-palmitoyl-D-erythro-sphinganine (DHC-16-Cer). The decrease in C16-Cer observed in both hypoxic and control RV's over time was paralleled by a significant increase in DHC-16-Cer in hypoxic (142.1+/-15.0 pmol; p<0.05) but not control (52.8+/-4.0 pmol) RV's suggesting a role for DHC-16-Cer in the RV adaptive response to hypoxia. Another species, N-arachidoyl-D-erythro-sphingosine (C20-Cer), was specifically and significantly decreased in the hypoxic RV. These studies support the presence of distinct roles for different ceramide species and their precursors. A better assessment of cyanotic congenital heart disease in light of the mechanism and timing of cardiomyocyte death, will lead to punctual interventions and even novel cardioprotective strategies.

Apoptosis and the activity of ceramide, Bax and Bcl-2 in the lungs of neonatal rats exposed to limited and prolonged hyperoxia.

BACKGROUND: The aim of the study is to examine the effect of limited and prolonged hyperoxia on neonatal rat lung. This is done by examining the morphologic changes of apoptosis, the expression of ceramide, an important mediator of apoptosis, the expression of inflammatory mediators represented by IL-1beta and the expression of 2 proto-oncogenes that appear to modulate apoptosis (Bax and Bcl-2). METHODS: Newborn rats were placed in chambers containing room air or oxygen above 90% for 7 days. The rats were sacrificed at 3, 7 or 14 days and their lungs removed. Sections were fixed, subjected to TUNEL, Hoechst, and E-Cadherin Staining. Sections were also incubated with anti-Bcl-2 and anti-Bax antisera. Bcl-2 and Bax were quantitated by immunohistochemistry. Lipids were extracted, and ceramide measured through a modified diacylglycerol kinase assay. RT-PCR was utilized to assess IL-1beta expression. RESULTS: TUNEL staining showed significant apoptosis in the hyperoxia-exposed lungs at 3 days only. Co-staining of the apoptotic cells with Hoechst, and E-Cadherin indicated that apoptotic cells were mainly epithelial cells. The expression of Bax and ceramide was significantly higher in the hyperoxia-exposed lungs at 3 and 14 days of age, but not at 7 days. Bcl-2 was significantly elevated in the hyperoxia-exposed lungs at 3 and 14 days. IL-1beta expression was significantly increased at 14 days. CONCLUSION: Exposure of neonatal rat lung to hyperoxia results in early apoptosis documented by TUNEL assay. The early rise in Bax and ceramide appears to overcome the anti-apoptotic activity of Bcl-2. Further exposure did not result in late apoptotic changes. This suggests that apoptotic response to hyperoxia is time sensitive. Prolonged hyperoxia results in acute lung injury and the shifting balance of ceramide, Bax and Bcl-2 may be related to the evolution of the inflammatory process.

Valor preditivo da trombomodulina sérica em pacientes com claudicação intermitente e com isquemia crítica de membros inferiores / Predictive value of the plasmatic levels of thrombomodulin in patients with intermittent claudication and critical ischemia in the lower limbs

A Trombomodulina é um marcador endotelial da doença aterosclerótica, e seu uso como preditor da doença arterial obstrutiva periférica (DAOP) deve ser comprovada. Avaliou-se 41 pacientes com claudicação intermitente e 40 com isquemia crítica. A Trombomodulina plasmática (TMp) foi quantificada em todos os pacientes, através de método imunoenzimático (ELISA). As hipóteses de normalidade e de homogeneidade de variância foram provadas, respectivamente, pelos testes de Shapiro-Wilk e de Levene. A comparação da TMp entre ambos os grupos foi realizada empregando-se o teste t de Student. A utilização de pacientes com Claudicação Intermitente e com Isquemia Crítica é interessante como modelo de estudo e deve ser empregado para avaliar diferentes marcadores de prognóstico da DAOP. Não foi observada diferença estatisticamente significante nos níveis de TMp nos grupos, não permitindo utilizar-se a TMp para avaliar o prognóstico da doença arterial obstrutiva periférica (DAOP) / Thrombomodulin (TM) is an endothelial marker of arterosclerotic disease and its use as a predictor of Peripheral Arterial Disease (PAD) must be proven. Forty-one patients having intermittent claudication and forty having critical ischemia were evaluated. Plasmatic Thrombomodulin (TMp) was quantified in all patients using the immunoenzymatic method (ELISA). The hypotheses of normality and variance homogeneity were proven, respectively, using the Wilk-Shapiro and Levene Tests. The comparison of the TMp between both groups was carried out using the Student-T Test. The utilization of patients with Intermittent Claudication and Critical Ischemia is interesting as a study model and should be used to evaluate different prognostic markers of PAD. No statistically significant difference was observed in the TMp levels between the groups, thus not permitting the use of TMp to evaluate the prognostics of Peripheral Arterial Disease (PAD)...

Regulation of the sphingolipid signaling pathways in the growing and hypoxic rat heart.

Sphingolipids (SLs) have a biomodulatory role in physiological as well as pathological cardiovascular conditions. This study aims to assess the variation of SL mediators and metabolizing enzymes in the growing and hypoxic rat heart. Sprague-Dawley rats were placed in a hypoxic environment at birth. Control animals remained in room air. In control animals, activities of acidic-sphingomyelinase (A-SMase), sphingomyelin synthase (SMS), glucosylceramide synthase (GCS), and ceramidase decreased with age in both ventricles whereas activity of neutral-sphingomyelinase (N-SMase) increased with age. Hypoxic RV mass was 171 and 229% that of controls, at 4 and 8 weeks, respectively. This was accompanied by an increase in RV myocardial ceramide synthesis, consumption and breakdown, with a net effect of suppression of ceramide accumulation and increase in diacylglycerol (DAG) concentration. In addition, significant increase in activities of: A-SMase by 26 and 29%, SMS by 108 and 40%, and ceramidase by 66 and 35%, in the hypoxic RV rats as compared to controls, was noted at 4 and 8 weeks of age, respectively. Sphingolipids and their regulating enzymes appear to play a role in adaptive responses to chronic hypoxia in the neonatal rat heart.

Tissue-specific ceramide response in the chronically hypoxic rat model mimicking cyanotic heart disease.

BACKGROUND AND OBJECTIVE: Acute hypoxia is associated with apoptosis and increase in ceramide levels in various organs. To assess the effect of chronic hypoxia on ceramide accumulation in the lungs and kidneys, we utilized an animal model mimicking cyanotic heart disease. METHODS: Rats were placed in a hypoxic environment at birth and oxygen levels were maintained at 10% in an air-tight Plexiglas chamber. Controls remained in room air. Animals were sacrificed and the lung and kidneys were harvested and weighed at 1 and 4 weeks, respectively. Ceramide levels were measured using a modified diacylglycerol kinase assay. RESULTS: Significant polycythemia developed in the hypoxic rats at 1 and 4 weeks. Indexed lung and kidney masses were significantly increased in the hypoxic animals as compared to controls at 1 and 4 weeks, respectively. The ceramide levels in the hypoxic lungs and kidneys were not significantly different from control groups at 1 and 4 weeks. [Ceramide/phosphate ratio in the kidneys was 1.28 +/- 0.17 (C) versus 1.18 +/- 0.12 (H) at 1 week; P = 0.39, and 1.46 +/- 0.08 (C) versus 1.33 +/- 0.15 (H) at 4 weeks (P = 0.44)] and [ceramide/phosphate ratio (pmol/nmol) in the lungs was 2.29 +/- 0.14 (C) versus 1.98 +/- 0.12 (H) at 1 week (P = 0.17), and 2.42 +/- 0.16 (C) versus 2.30 +/- 0.05 (H) at 4 weeks, P = 0.34]. CONCLUSION: The response of lungs and kidneys to chronic hypoxia includes increase in indexed mass and lack of ceramide accumulation. This is similar to the response previously reported in the chronically hypoxic brain and heart. Thus, various organs appear to have similar ceramide response pattern to chronic hypoxia.

Endocrine changes in a rat model of chronic hypoxia mimicking cyanotic heart disease.

OBJECTIVE: The endocrine system plays an important role in the adaptation to hypoxia. The aim of this study is to assess the effect of chronic hypoxia on endocrine changes in a neonatal animal model mimicking cyanotic heart disease. METHODS: Sprague-Dawley rats were placed in a normobaric hypoxic environment at birth and oxygen levels were maintained at 10% in an airtight Plexiglas chamber. Controls remained in room air. Animals were sacrificed at 4 and 8 weeks of life. Hematocrit, Free T4 (FT4), Thyrotropin (TSH), corticosterone, and Growth hormone (GH) were measured. RESULTS: Significant polycythemia developed in the hypoxic rats. Free T4 levels were significantly lower in the hypoxic (H) group compared to the control (C) group at 4 and 8 weeks with FT4 of 2.44 +/- 1.11 ng/dL (H) and 4.35 +/- 1.62 (C) at 4 weeks with a p value < 0.005 and FT4 of 2.01 +/- 0.36 (H) and 3.25 +/- 0.54 (C) ng/dL at 8 weeks with p < 0.01. At 8 weeks TSH levels were significantly lower in the hypoxic group (1.84 +/- 0.9 ng/mL (H) vs. 3.11 +/- 1.1 (C)) with p < 0.05. Corticosterone levels were higher in the hypoxic group with values of 126 +/- 14.8 ng/mL (H) and 114.1 +/- 12.6 (H) at 4 and 8 weeks respectively, when compared to the control group with values of 82.9 +/- 18.1 (C) and 92.7 +/- 10.3 (C) and 4 and 8 weeks with p < 0.0005 and < 0.05 respectively. Growth hormone levels were lower in the hypoxic group at 4 and 8 weeks with p < 0.05 and p < 0.001, respectively. CONCLUSION: Chronic hypoxia in our neonatal rat model was associated with decrease in growth hormone levels and an increase in corticosterone levels. Furthermore, hypoxia resulted in thyroid hormone axis suppression. This effect seems to centrally mediated.

Cardiac growth patterns in response to chronic hypoxia in a neonatal rat model mimicking cyanotic heart disease.

OBJECTIVE: Myocardial growth during fetal life is accomplished by the proliferation of myocytes. Shortly after birth, normal myocytes largely lose their capability to replicate. The present study aims to assess the effect of persistent postnatal hypoxia on myocardial growth patterns in an animal model mimicking cyanotic heart disease. METHODS: Sprague-Dawley rats were placed in a normobaric hypoxic environment at birth and oxygen levels were maintained at 10% (group H). Controls (group C) remained in room air. The animals were sacrificed and the hearts were harvested at one, four and eight weeks. RESULTS: Significant polycythemia developed in the hypoxic rats. There was a significant increase in indexed right ventricle (RV) and left ventricle (LV) masses compared with controls. Myocardial DNA concentrations were significantly increased in both ventricles of the hypoxic rats. For the RV, the increase in DNA content for group H was 135%, 132% and 112% that of group C values at one, four and eight weeks, respectively. RV and LV myocardial protein:DNA ratios were lower in the one-week- and four-week-old hypoxic rats, and significantly higher in the hypoxic eight-week-old rats. Polyploidy, hydroxyproline concentrations and dry:wet weight ratios were not significantly different in the LV and RV between both group H and group C animals. CONCLUSION: Cardiac mass increases in response to chronic hypoxia were greater in the RV than the LV. This increase was mainly due to myocardial proliferation in the first four weeks of life. Although the three groups of hypoxic rats had significant elevations in DNA concentration compared with controls, there was a shift from proliferation to hypertrophy after week 4 of life. The age of the myocyte appears to be the most important factor in triggering proliferation in this hypoxic animal model.

Lack of apoptosis in the hypoxic brain of a rat model mimicking cyanotic heart disease.

OBJECTIVE: To assess the effect of chronic hypoxia on brain neuronal apoptosis, an animal model mimicking cyanotic heart disease was utilized. METHODS: Rats were placed in an hypoxic environment at birth and oxygen levels were maintained at 10% in an air-tight Plexiglass chamber. Controls remained in room air. Animals were sacrificed and the brains were harvested at 1 and 4 weeks, respectively. RESULTS: Significant polycythemia developed in the hypoxic rats at 1 and 4 weeks. Indexed brain mass to body weight was significantly increased in the hypoxic groups by 18% (p < 0.01) and 38% (p < 0.01) as compared to controls at 1 and 4 weeks, respectively. There was no difference in the number of apoptotic neurons between the chronically hypoxic rats and controls, as assayed by TUNEL labelling and Hoechst staining. The role of the sphingolipid ceramide was then examined because of its reported role in stress response, growth suppression and apoptosis. It was found that the brain ceramide accumulation was not significantly different in the hypoxic and control groups at 1 and 4 weeks. CONCLUSION: A protective adaptive response to chronic hypoxia in the neonatal brain may exist.