Aortic isthmus doppler velocimetry in fetuses with intrauterine growth restriction: A literature review / Dopplervelocimetria do istmo aórtico em fetos com crescimento intrauterino restrito: Uma revisão da literatura

Abstract Intrauterine growth restriction (IUGR) is associated with poor perinatal prognosis and a higher risk of stillbirth, neonatal death, and cerebral palsy. Its detection and the evaluation of its severity by new Doppler velocimetric parameters, such as aortic isthmus (AoI), are of great relevance for obstetrical practice. The AoI is a vascular segment that represents a point of communication between the right and left fetal circulations. It is considered to be a functional arterial shunt that reflects the relationship between the systemic and cerebral impedances, and has recently been proposed as a tool to detect the status of hemodynamic balance and prognosis of IUGR in fetuses. In the present review, we noticed that in healthy fetuses, the AoI net flow is always antegrade, but in fetuses with IUGR the deterioration of placental function leads to progressive reduction in its flow until it becomes mostly retrograde; this point is associated with a drastic reduction in oxygen delivery to the brain. The more impaired the AoI flow is, the greater is the risk of impairment in the Doppler velocimetry of other vessels; and the alterations of the AoI Doppler seem to precede other indicators of severe hypoxemia. Although there seems to be an association between the presence of retrograde flow in the AoI and the risk of long-term neurologic disability, its role in the prediction of perinatal morbi-mortality remains unclear. The AoI Doppler seems to be a promising tool in the management of fetuses with IUGR, but more studies are needed to investigate its employment in clinical practice.

Resumo O crescimento intrauterino restrito (CIUR) está associado a um prognóstico perinatal adverso, com maior risco de óbito intrauterino e neonatal, bem como de paralisia cerebral. Assim, sua detecção e a determinação de sua gravidade por novos parâmetros Dopplervelocimétricos, como o istmo aórtico (IAo), são de fundamental importância na prática obstétrica. O IAo é um segmento vascular que representa um ponto de comunicação entre os sistemas circulatórios fetais esquerdo e direito. É considerado um shunt arterial funcional, capaz de refletir a relação entre as impedâncias dos circuitos cerebral e sistêmico, e foi proposto como uma ferramenta para detecção do status do equilíbrio hemodinâmico e do prognóstico de fetos com CIUR. Na presente revisão, observou-se que, em fetos saudáveis, o fluxo predominante no IAo é sempre anterógrado; mas em fetos com CIUR a deterioração do estágio de insuficiência placentária acarreta reduções progressivas no fluxo ístmico até este apresentar sentido predominantemente retrógrado e levar a uma drástica redução no aporte de oxigênio ao sistema nervoso central. Quanto mais alterado estiver o fluxo no IAo, maior a chance de haver alteração na Dopplervelocimetria de outros vasos; e as alterações no Doppler do IAo parecem preceder outros indicadores de hipoxemia severa. Embora o fluxo retrógrado no IAo pareça se correlacionar com maior risco de alteração no desenvolvimento neurológico a longo prazo, ainda não está claro o seu papel na predição de morbimortalidade perinatal. O Doppler do IAo parece ser um parâmetro promissor no manejo do CIUR; entretanto, mais estudos são necessários para avaliar seu emprego na prática clínica.

Mortality and survival in aortic arch surgeries with preservation of supra-aortic vessels: thirteen years of experience / Mortalidade e sobrevida em cirurgias do arco aórtico com preservação de vasos supra-aórticos: treze anos de experiência

Background: The aortic arch diseases exhibit high morbidity and mortality rates. Some surgical strategies recommend partial preservation of the aortic arch and the supra-aortic vessels, but the immediate and mediumterm mortality rates of patients undergoing this surgical strategy is uncertain. Objectives: To compare overall mortality and mid- term survival curve of patients undergoing surgical strategy of partial preservation of the aortic arch and supra-aortic vessels (group A) compared to conventional strategies of the aortic arch approach (group B); to assess cardiovascular mortality over time. Methods: Descriptive and retrospective study of the medical records of patients undergoing aortic arch repair surgery between February 2000 and July 2013. We analyzed 111 patients, 29 in group A and 82 in group B. The overall survival and survival from cardiovascular events were assessed by Kaplan-Meier test. Results: In- hospital mortality from any cause was 31% in group A and 29.3% in group B. At 1 year, 2 year, and 5 year general survival was similar between the groups. In-hospital, 2 years and 5 years mortality from cardiovascular causes was 13.8%, 14.8%, e 22.7% in group A and 26.8%, 34.6% e 50.9% in group B. The difference between the groups in 5 years showed statistical significance (p = 0.0234). Survival from cardiovascular causes in 2 years and 5 years was 85.2% and 77,3% in group A and 65.4% and 49,1% in group B. Occurrence of urgent and emergency procedures were greater in group A, but without statistical significance. Conclusions: There was no difference in all-cause mortality over time between the groups. Group A showed lower cardiovascular mortality at 5 years than group B

Avaliação das dimensões da aorta torácica ao ecocardiograma transtóracico bidimensional: correlação com fatores de risco cardiovasculares / Transthoracic echocardiographic assessment of thoracic aorta: correlation with cardiovascular risk factors

Fundamentos: As dimensões da aorta torácica têm tido fraca correlação com fatores de risco cardiovasculares, como hipertensão arterial sistêmica (HAS), diabetes mellitus (DM) e doença arterial coronariana (DAC). Objetivos: Correlacionar o diâmetro da aorta torácica avaliado pelo ecocardiograma transtorácico (ETT) com HAS, DM, dislipidemia, DAC, tabagismo, idade, sexo, peso, altura, índice de massa corpórea (IMC) e superfície corporal (SC), além de uso contínuo de medicamentos com ação protetora cardiovascular. Métodos: Estudo observacional, transversal e retrospectivo. Foram selecionados 203 indivíduos (62,1 ± 15,3 anos; 57,1% do sexo feminino) que realizaram ETT com a avaliação da aorta torácica em 6 sítios: (1) anel valvar aórtico; (2) seio de valsalva; (3) junção sino tubular; (4) aorta proximal ascendente; (5) arco aórtico e (6) aorta descendente. Resultados: Idade (p < 0,05), sexo masculino (p < 0,001), peso (p < 0,001), altura (p < 0,05) e SC(p < 0,001) foram associados a maiores diâmetros da aorta torácica em todos os sítios de avaliação. A análise multivariada identificou que idade, sexo masculino e SC, conjuntamente, explicam a variação dos diâmetros no anel aórtico em 17,3%, no seio de valsalva, em 30,7%, na junção sino tubular em 17,7%, na ascendente proximal em 21,9%, no arco aórtico em 19,8% e na aorta descendente em 21,4%. Não houve associação entre os diâmetros da aorta e os fatores de risco avaliados e uso contínuo de betabloqueadores, inibidores da enzima conversora de angiotensina ou bloqueadores dos receptores da angiotensina. Conclusões: Idade, sexo masculino e superfície corpórea se correlacionaram positiva e significativamente com os diâmetros da aorta torácica

Background: Thoracic aorta dimensions have been poorly correlated with cardiovascular risk factors such as systemic arterial hypertension (SAH), diabetes mellitus (DM) and coronary artery disease (CAD). Objectives: To correlate the thoracic aorta diameter assessed by transthoracic echocardiography (TTE) with SAH, DM, dyslipidemia, CAD, smoking, age, gender, weight, height, body mass index (BMI) and body surface area (BSA) and continuous use of drugs with cardiovascular protective action. Methods: Observational, cross-sectional and retrospective study. The study included 203 individuals (62.1 ± 15.3 years of age; 57.1% female) who underwent TTE with thoracic aorta evaluation at 6 sites: (1) aortic valve annulus; (2) sinus of Valsalva; (3) sinotubular junction; (4) ascending proximal aorta; (5) aortic arch and (6) descending aorta.Results: Age (p < 0.05), male gender (p < 0.001), weight (p < 0.001), height (p < 0.05), and BSA (p < 0.001) were associated with greater thoracic aorta diameters at all sites evaluated. Multivariate analysis identified that age, male gender and BSA, together, explain the variation of aortic annulus diameters in 17.3%, in the sinus of Valsalva in 30.7%, in the sinotubular junction in 17.7%, in the proximal ascending aorta in 21.9%, in the aortic arch in 19.8% and in the descending aorta in 21.4%. There was no association between aortic diameters and the risk factors assessed and continuous use of beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Conclusions: Age, male gender and body surface area correlated positively and significantly with the thoracic aorta diameters

Aerobic Swim Training Restores Aortic Endothelial Function by Decreasing Superoxide Levels in Spontaneously Hypertensive Rats

OBJECTIVE: We aimed to determine whether aerobic training decreases superoxide levels, increases nitric oxide levels, and improves endothelium-dependent vasodilation in the aortas of spontaneously hypertensive rats. METHODS: Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were distributed into 2 groups: sedentary (SHRsd and WKYsd, n=10 each) and swimming-trained (SHRtr, n=10 and WKYtr, n=10, respectively). The trained group participated in training sessions 5 days/week for 1 h/day with an additional work load of 4% of the animal’s body weight. After a 10-week sedentary or aerobic training period, the rats were euthanized. The thoracic aortas were removed to evaluate the vasodilator response to acetylcholine (10-10 to 10-4 M) with or without preincubation with L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10-4 M) in vitro. The aortic tissue was also used to assess the levels of the endothelial nitric oxide synthase and nicotinamide adenine dinucleotide oxidase subunit isoforms 1 and 4 proteins, as well as the superoxide and nitrite contents. Blood pressure was measured using a computerized tail-cuff system. RESULTS: Aerobic training significantly increased the acetylcholine-induced maximum vasodilation observed in the SHRtr group compared with the SHRsd group (85.9±4.3 vs. 71.6±5.2%). Additionally, in the SHRtr group, superoxide levels were significantly decreased, nitric oxide bioavailability was improved, and the levels of the nicotinamide adenine dinucleotide oxidase subunit isoform 4 protein were decreased compared to the SHRsd group. Moreover, after training, the blood pressure of the SHRtr group decreased compared to the SHRsd group. Exercise training had no effect on the blood pressure of the WKYtr group. CONCLUSIONS: In SHR, aerobic swim training decreased vascular superoxide generation by nicotinamide adenine dinucleotide oxidase subunit isoform 4 and increased nitric oxide bioavailability, thereby improving endothelial function.

A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats / Uma Única Sessão de Exercício Resistido Melhora a Função Endotelial Aórtica em Ratos Hipertensos

Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR). Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS1177) and inducible nitric oxide synthase (iNOS) and to generate concentration-response curves to acetylcholine (ACh) and to phenylephrine (PHE). The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin administration. The maximal response (Emax) and the sensitivity (EC50) to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex) rats (Emax= -80 ± 4.6%, p < 0.05) when compared to those of controls (Ct) (Emax = -50 ± 6.8%). The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05) when compared to control conditions (120 ± 4.2%). This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05). Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

Resumo Fundamento: O exercício físico é uma importante ferramenta para o aprimoramento da função endotelial. Objetivo: Avaliar os efeitos do exercício dinâmico resistido agudo na função endotelial de ratos espontaneamente hipertensos (SHR). Métodos: Após 10 minutos de exercício, a aorta foi removida para avaliação da expressão de óxido nítrico sintase endotelial (eNOS), óxido nítrico sintase endotelial fosforilada (p-eNOS1177) e óxido nítrico sintase endotelial induzível (iNOS), e para a construção de curvas concentração-resposta de acetilcolina (ACT) e fenilefrina (FEN). O protocolo FEN foi também realizado com lesão endotelial e antes e depois da administração de N-nitro-L-arginina metil éster (L-NAME) e indometacina. A resposta máxima (Emax) e a sensibilidade (EC50) a esses fármacos foram avaliadas. Resultados: Houve aumento do relaxamento induzido por ACT nos anéis aórticos dos ratos exercitados (Ex) (Emax = -80 ± 4,6%; p < 0,05) quando comparado àquele dos controles (Ct) (Emax = -50 ± 6,8%). A Emax à FEN diminuiu após exercício (95 ± 7,9%; p < 0,05) quando comparada àquela dos controles (120 ± 4,2%). Tal resposta foi abolida após administração de L-NAME ou lesão endotelial. Na presença de indometacina, a reatividade dos anéis aórticos à FEN diminuiu nos dois grupos (EC50= Ex -5,9 ± 0,14 vs. Ct -6,6 ± 0,33 log µM; p < 0,05/ Emax = Ex 9,5 ± 2,9 vs. Ct 17 ± 6,2%; p < 0,05). O exercício não alterou a expressão de eNOS e de iNOS, mas aumentou o nível de p-eNOS. Conclusão: Uma única sessão de exercício resistido melhora a função endotelial em ratos hipertensos. Essa resposta parece ser mediada por elevação da produção de NO através de ativação de eNOS.

Role of adenylyl cyclase in reduced ß-adrenoceptor-mediated vasorelaxation during maturation

Beta-adrenergic receptor (βAR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of βAR subtypes (β1AR, β2AR, and β3AR) and cAMP in maturation-dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium. Vascular relaxation in aortic rings from younger and older groups was compared in the presence of βAR subtype agonists and antagonists along with cAMP and cGMP antagonists. Isolated aortic rings were used to evaluate relaxation responses, protein expression was evaluated by western blot or real time PCR, and metabolites were measured by ELISA. Expression of βAR subtypes and adenylyl cyclase was assessed, and cAMP activity was measured in vascular tissue from both groups. Isoproterenol- and BRL744-dependent relaxation in aortic rings with and without endothelium from 9-week-old rats was impaired compared with younger rats. The β1AR antagonist CGP20712A (10-7 M) did not affect isoproterenol or BRL744-dependent relaxation in arteries from either group. The β2AR antagonist ICI-118,551 (10-7 M) inhibited isoproterenol-dependent aortic relaxation in both groups. The β3AR antagonist SR59230A (10-7 M) inhibited isoproterenol- and BRL744-dependent aortic ring relaxation in younger but not in older rats. All βAR subtypes were expressed in both groups, although β3AR expression was lower in the older group. Adenylyl cyclase (SQ 22536) or protein kinase A (H89) inhibitors prevented isoproterenol-induced relaxation in younger but not in older rats. Production of cAMP was reduced in the older group. Adenylyl cyclase III and RyR3 protein expression was higher in the younger group. In conclusion, altered expression of β3AR and adenylyl cyclase III may be responsible for reduced cAMP production in the older group.

Inhibition of PKC-dependent extracellular Ca2+ entry contributes to the depression of contractile activity in long-term pressure-overloaded endothelium-denuded rat aortas

We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.

Multislice CT Scans in Patients on Extracorporeal Membrane Oxygenation: Emphasis on Hemodynamic Changes and Imaging Pitfalls

This pictorial review provides the principles of extracorporeal membrane oxygenation (ECMO) support and associated CT imaging features with emphasis on the hemodynamic changes and possible imaging pitfalls encountered. It is important that radiologists in ECMO centers apply well-designed imaging protocols and familiarize themselves with post-contrast CT imaging findings in patients on ECMO.

Medición de presiones relativas en aorta torácica y arteria pulmonar de voluntarios sanos y pacientes con Tetralogía de Fallot reparada utilizando la secuencia 4D Flow de resonancia magnética cardíaca / Relative pressure measurement in thoracic aorta and pulmonary artery in healthy volunteers and patients with Tetralogy of Fallot repaired by 4D Flow cardiovascular MRI

Objective. To validate the utility of 4D Blood Flow and Navier-Stokes equations to create relative pressure (RP) maps in the aorta and pulmonary artery (PA) in healthy volunteers and patients with repaired tetralogy of Fallot (TOF). Methods. A 4D flow sequence of whole heart and its major vessels was acquired in 10 healthy volunteers and 6 patients with repaired TOF. The root of the ascending aorta was used as the reference point to calculate RP along five different points of this area. In addition, relative pressure of both right and left PA was measured as correlated to absolute pressure. Results. Patients with repaired TOF showed greater pulmonary artery (PA) relative pressure differences between maximum and minimum values when compared to volunteers (p <0.05). Additionally, aortic relative pressures had an excellent correlation with published data, whether using 4D flow or by catheterization. Conclusions. 4D Flow MRI may represent a new non-invasive and non operator-dependent diagnostic tool in CV disease management.

Objetivo. Utilizar 4D Flow y las ecuaciones de Navier-Stokes para obtener mapas de presiones relativas (PR) en la Aorta y Arteria Pulmonar (AP) de voluntarios y pacientes con Tetralogía de Fallot reparada (TOFr). Métodos. En 10 voluntarios y 6 pacientes con TOFr se adquirió la secuencia 4D flow del corazón y sus principales vasos. La raíz de la Aorta Ascendente se utilizó como referencia para calcular las PR a esta zona en cinco puntos distintos. Además, se midió la PR de la AP derecha e izquierda respecto a la AP. Resultados. Los pacientes con TOFr tuvieron diferencias de PR entre los valores máximos y mínimos más grandes que los voluntarios en la AP (p<0,05). Adicionalmente, las PR de la aorta tuvieron una excelente correlación con datos publicados utilizando 4D flow y mediante cateterización. Conclusiones. 4D Flow podría constituir una nueva herramienta diagnóstica, no invasiva, ni operador dependiente, en el manejo de patologías CV.

Alterações vasculares em ratos obesos por dieta rica em gordura: papel da Via L-arginina/NO Endotelial / Vascular alterations in high-fat diet-obese rats: role of Endothelial L-arginine/NO Pathway / Alteraciones vasculares en ratones obesos por dieta rica en grasa: papel de la vía L-arginina/NO endotelial

FUNDAMENTO: Mecanismos subjacentes a anormalidades vasculares na obesidade ainda não estão completamente esclarecidos. OBJETIVO: Foi avaliada a via do óxido nítrico/L-arginina na resposta vascular de ratos obesos por dieta rica em gordura, enfocando as células endoteliais e do músculo liso. MÉTODOS: Ratos com 30 dias de vida foram divididos em 2 grupos: controle (C) e obeso (OB, ratos sob dieta rica em gordura por 30 semanas). Após 30 semanas, foram registrados o peso corporal, índice de adiposidade, pressão arterial e perfis metabólicos e endócrinos dos animais. Foram obtidas curvas para noradrelanina na ausência e presença de inibidor de óxido nítrico sintase (L-NAME, 3x10-4M) em aorta torácica intacta e com desnudamento em ratos C e OB. RESULTADOS: As medidas de peso corporal, índice de adiposidade, leptina e insulina aumentaram nos ratos OB, enquanto a pressão arterial permaneceu inalterada. A obesidade também produziu tolerância à glicose e resistência à insulina. A reatividade à noradrenalina da aorta intacta foi similar em ratos C e OB. A presença de L-NAME produziu um aumento similar nas respostas máximas, mas um desvio maior à esquerda das respostas nas aortas intactas dos ratos C em relação aos ratos OB [EC50 (x10-7M): C = 1,84 (0,83-4,07), O = 2,49 (1,41-4,38); presença de L-NAME C = 0,02 (0,01-0,04)*, O = 0,21 (0,11-0,40)*†,*p < 0,05 vs controle respectivo,†p < 0,05 vs controle mais L-NAME, n = 6-7]. Nenhum dos protocolos alterou a reatividade à noradrenalina de aortas com desnudamento. CONCLUSÃO: A obesidade induzida por dieta rica em gordura promove alterações metabólicas e vasculares. A alteração vascular envolveu uma melhora da via endotelial L-arginina/NO provavelmente relacionada à hiperinsulinemia e hiperleptinemia induzidas por dieta. A maior resistência aos efeitos do L-NAME na aorta de ratos obesos diz respeito a menor vulnerabilidade de indivíduos obesos na presença de patologias associadas que causam danos à atividade do sistema NO.

BACKGROUND: Mechanisms underlying vascular abnormalities in obesity remain to be completely clarified. OBJECTIVE: L-arginine/nitric oxide pathway was evaluated on vascular response of high-fat diet-obese rats, focusing on endothelial and smooth muscle cells. METHODS: 30-day-old rats were divided in two groups: control (C) and obese (OB, high-fat diet for 30 weeks). After 30 weeks, body weight, adiposity index, blood pressure, and metabolic and endocrine profiles of the animals were recorded. Curves to noradrenaline were obtained in absence and presence of nitric oxide synthase inhibitor (L-NAME, 3x10-4M) on intact and denuded thoracic aorta from C and OB rats. RESULTS: Body weight, adiposity index, leptin and insulin levels were increased in OB, while blood pressure was unchanged. Obesity also produced glucose tolerance and insulin resistance. Reactivity to noradrenaline of intact aorta was similar in C and OB rats. L-NAME presence produced a similar increase in maximal responses, but a higher leftward shift of noradrenaline responses in intact aorta from C than in OB rats [EC50 (x10-7M): C = 1.84 (0.83-4.07), O = 2.49 (1.41-4.38); L-NAME presence C = 0.02 (0.01-0.04)*, O = 0.21 (0.11-0.40)*†,*p < 0.05 vs respective control, †p < 0.05 vs control plus L-NAME, n = 6-7]. None of the protocols altered the reactivity to noradrenaline of denuded aortas. CONCLUSION: High-fat diet-induced obesity promotes metabolic and vascular alterations. The vascular alteration involved an endothelial L-arginine/NO pathway improvement was probably correlated to diet-induced hyperinsulinemia and hyperleptinemia. The greater resistance to L-NAME effects in aorta of obese rats raises concerns about the lower cardiovascular vulnerability of obese individuals in the presence of associated pathologies that impair NO-system activity.

FUNDAMENTO: Los mecanismos subyacentes a las anormalidades vasculares en la obesidad todavía no están completamente aclarados. OBJETIVO: Se evaluó la vía del óxido nítrico/L-arginina en la respuesta vascular de ratones obesos por dieta rica en grasa, concentrándonos en las células endoteliales y en el músculo liso. MÉTODOS: Ratones con 30 días de vida que fueron divididos en 2 grupos: control (C) y obeso (OB, ratones bajo dieta rica en grasa durante 30 semanas). Después de 30 semanas, fueron registrados el peso corporal, el índice de adiposidad, la presión arterial y los perfiles metabólicos y endocrinos de los animales. Fueron obtenidas las curvas para noradrelanina en ausencia y en presencia del inhibidor de óxido nítrico sintasa (L-NAME, 3x10-4M), en la aorta torácica intacta y con denudación de los ratones C y OB. RESULTADOS: Las medidas de peso corporal, índice de adiposidad, leptina e insulina aumentaron en los ratones OB, mientras que la presión arterial permaneció inalterada. La obesidad también produjo una tolerancia a la glucosa y una resistencia a la insulina. La reactividad a la noradrenalina de la aorta intacta fue similar en los ratones C y OB. La presencia de L-NAME generó un aumento similar en las respuestas máximas, pero una desviación mayor a la izquierda de las respuestas en las aortas intactas de los ratones C con relación a los ratones OB [EC50 (x10-7M): C = 1,84 (0,83-4,07), O = 2,49 (1,41-4,38); presencia de L-NAME C = 0,02 (0,01-0,04)*, O = 0,21 (0,11-0,40)*†,*p < 0,05 vs control respectivo, †p < 0,05 vs control más L-NAME, n = 6-7]. Ninguno de los protocolos alteró la reactividad a la noradrenalina de las aortas con denudación. CONCLUSIÓN: La obesidad inducida por dieta rica en grasa genera alteraciones metabólicas y vasculares. La alteración vascular conllevó a una mejoría de la vía endotelial L-arginina/NO tal vez relacionada con la hiperinsulinemia e hiperleptinemia inducidas por dieta. La mayor resistencia a los efectos del L-NAME en la aorta de ratones obesos, se refiere a una menor vulnerabilidad de individuos obesos en presencia de patologías asociadas que causan daños a la actividad del sistema NO.

Effect of soft tissue crush injury on tensions of thoracic aortic rings in rats / 法医学杂志

OBJECTIVE@#To observe the effect of soft tissue crush injury on the tensions of thoracic aortic rings (TARs) in rats and to investigate the potential roles of nitric oxide in the change of the tensions.@*METHODS@#Thirty adult SD rats were randomly divided into control group and crush injury (8 h and 16 h after injury) groups. Two kinds of TARs (one with endothelium and the other without endothelium) in vitro were prepared. In the TARs with endothelium, the tensions induced by phenylephrine (PE), acetylcholine (Ach), calcium ionophore A23187 and angiotensin II (AngI) were measured by the vascular tension detective technique. Then the TARs with endothelium were preincubated with nitric oxide synthase inhibitor N-nitro-L-arginine (L-NNA) for 20 minutes, the tensions induced by PE and Ang II were measured again. In the TARs without endothelium, the tensions induced by PE and Ang II were measured by the same method.@*RESULTS@#In the TARs with endothelium, the tension of relaxation induced by cumulative doses of Ach and A23187 decreased significantly in 8 h and 16h groups. The tension of contraction induced by cumulative doses of PE and Ang II also decreased significantly (P<0.05). The tension of contraction increased after the preincubation with L-NNA. In the TARs without endothelium, the tension of contraction induced by PE and Ang II increased comparing to that of TARs with endothelium.@*CONCLUSION@#The soft tissue crush injury can influence the tensions of TARs in rats and the vascular-derived NO can mediate the effects.

4D FLOW: una nueva herramienta de diagnóstico para cardiopatías congénitas / 4D Flow MRI: a new diagnostic tool for congenital heart diseases

Purpose. To demonstrate the utility of 4D flow MR imaging for analyzing blood flow patterns and flow distribution in patients with congenital heart diseases. Methods: Six patients with congenital heart diseases were scanned using a standard cardiac MRI protocol, according to their condition. Additionally, 2D flow sequences of the great vessels, and a 4D flow sequence covering the entire heart were acquired. Flow patterns were visualized by using vector fields, streamlines and particle traces. Results: 4D flow technique depicted vortices and helical flow in the pulmonary artery of most patients, as well as in the aorta and superior vena cava of one patient with corrected aortic coarctation and a levoatrial cardinal vein. Conclusion: 4D flow MR imaging enables the identification of flow patterns difficult to detect with other diagnostic modalities. Comprehensive evaluation of flow patterns might help to understand the hemodynamic consequences of congenital heart diseases and their surgical procedures.

Objetivo. Demostrar la utilidad de 4D flow para el análisis de patrones y distribución de flujos en pacientes con cardiopatías congénitas. Métodos: Seis pacientes con cardiopatías congénitas fueron escaneados con un protocolo de resonancia magnética cardíaca estándar. Además se incluyeron secuencias de flujo 2D en los principales vasos del tórax y una secuencia 4D flow que cubría todo el corazón. Para la visualización de los patrones de flujo se emplearon vectores de velocidad, líneas de flujo y trazadores de partículas. Resultados: 4D flow reveló vórtices y hélices en la arteria pulmonar de la mayoría de los pacientes, y en la aorta y vena cava superior de un paciente con coartación aórtica reparada y vena cardinal levoatrial. Conclusiones: 4D flow permite identificar patrones de flujo en pacientes con cardiopatías congénitas, difíciles de observar con otros métodos diagnósticos. La evaluación de patrones de flujo podría contribuir a comprender las consecuencias hemodinámicas de diferentes cardiopatías congénitas.

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats / Estresse oxidativo não está associado à disfunção vascular em um modelo de diabetes induzida por aloxana em ratos

OBJECTIVES: To verify if an experimental model of alloxan-diabetic rats promotes oxidative stress, reduces nitric oxide bioavailability and causes vascular dysfunction, and to evaluate the effect of N-acetylcysteine (NAC) on these parameters. METHODS: Alloxan-diabetic rats were treated or not with NAC for four weeks. Plasmatic levels of malondialdehyde (MDA) and nitrite/nitrate (NOx), the endothelial and inducible nitric oxide synthase (eNOS and iNOS) immunostaining and the vascular reactivity of aorta were compared among diabetic (D), treated diabetic (TD) and control (C) rats. RESULTS: MDA levels increased in D and TD. NOx levels did not differ among groups. Endothelial eNOS immunostaining reduced and adventitial iNOS increased in D and TD. The responsiveness of rings to acetylcholine, sodium nitroprusside, and phenylephrine did not differ among groups. CONCLUSIONS: NAC had no effect on the evaluated parameters and this experimental model did not promote vascular dysfunction despite the development of oxidative stress.

OBJETIVOS: Verificar se um modelo experimental de diabetes por aloxana promove estresse oxidativo, reduz a disponibilidade de óxido nítrico e causa disfunção vascular, e avaliar o efeito da N-acetilcisteína (NAC) nesses parâmetros. MÉTODOS: Ratos diabéticos por aloxana foram tratados com NAC por quatro semanas. Níveis plasmáticos de malondialdeído (MDA) e nitrito/nitrato (NOx), imunomarcação para óxido nítrico sintase endotelial e induzida (eNOS e iNOS) e reatividade vascular da aorta foram comparados entre ratos diabéticos (D), diabéticos tratados (TD) e controles (C). RESULTADOS: O MDA aumentou nos grupos D e TD. O NOx não diferiu entre os grupos. A marcação da eNOS no endotélio reduziu e a da iNOS na adventícia aumentou nos grupos D e TD. A responsividade dos anéis vasculares à acetilcolina, nitroprussiato de sódio e fenilefrina não diferiu entre os grupos. CONCLUSÕES: A NAC não teve efeito sobre os parâmetros avaliados. Esse modelo experimental não promoveu disfunção vascular apesar do desenvolvimento de estresse oxidativo.

Evaluación de la función cardiovascular en fetos con restricción de crecimiento / Cardiac function in fetus with growth restriction

Objective: To evaluate longitudinal changes in the cardiac function parameters in relation to the hemodynamic worsening in growth restricted (IUGR) fetuses. Methods: The cardiac function was serially studied in a cohort of 46 IUGR fetuses below 32 weeks of gestation by 2-D and Doppler ultrasound parameters. IUGR was defined as an estimated fetal weight below the 10th percentile with a Doppler pulsatility index (PI) in the umbilical artery (UA) above 2 standard deviations of the mean. Longitudinal changes, perinatal deaths and survivors were evaluated. Results: All cardiac parameters were significantly different in IUGR fetuses. Aortic isthmus blood flow index (IFI) and Modified myocardial performance index (Mod-MPI) showed the clearest longitudinal changes and temporal deterioration. Conclusions: IFI and Mod-MPI showed consistent longitudinal changes in IUGR fetuses. These 2 markers could be added to the DV to evaluate the fetal deterioration and indicate the optimal time of delivery.

Objetivo: Evaluar cambios longitudinales de los parámetros de función cardíaca en relación al agravamiento hemodinámico en fetos con restricción del crecimiento intrauterino (RCIU). Métodos: La función cardíaca fue estudiada en una cohorte de 46 fetos RCIU con menos de 32 semanas de gestación con parámetros 2-D y ultrasonografía Doppler. Se definió RCIU como un peso fetal estimado bajo el percentil 10 asociado a un índice de pulsatilidad (IP) al Doppler de la arteria umbilical (AU) por debajo de dos desviaciones estándar del promedio. Se evaluaron cambios longitudinales, mortalidad y sobrevida perinatal. Resultados: Todos los parámetros tuvieron diferencias estadísticamente significativas en fetos RCIU. El índice de velocidad de flujo del istmo aórtico (IFI) y el índice de función miocárdico modificado (IFM-mod) mostraron los más evidentes cambios longitudinales y deterioro en el tiempo. Conclusiones: El IFI y el IFM-mod mostraron consistentes cambios longitudinales en fetos RCIU. Estos dos marcadores podrían ser usados junto a la medición del ductus venoso para evaluar el deterioro fetal y la indicación óptima del momento del parto.

Purine nucleotides reduce superoxide production by nitric oxide synthase in a murine sepsis model

Sepsis involves a systemic inflammatory response of multiple endogenous mediators, resulting in many of the injurious and sometimes fatal physiological symptoms of the disease. This systemic activation leads to a compromised vascular response and endothelial dysfunction. Purine nucleotides interact with purinoceptors and initiate a variety of physiological processes that play an important role in maintaining cardiovascular function. The purpose of the present study was to investigate the effects of ATP on vascular function in a lipopolysaccharide (LPS) model of sepsis. LPS induced a significant increase in aortic superoxide production 16 h after injection. Addition of ATP to the organ bath incubation solution reduced superoxide production by the aortas of endotoxemic animals. Reactive Blue, an antagonist of the P2Y receptor, blocked the effect of ATP on superoxide production, and the nonselective P2Y agonist MeSATP inhibited superoxide production. Nitric oxide synthase (NOS) inhibition by L-NAME blocked vascular relaxation and reduced superoxide production in LPS-treated animals. In the presence of L-NAME there was no ATP effect on superoxide production. A vascular reactivity study showed that ATP increased maximal relaxation in LPS-treated animals compared to controls. The presence of ATP induced increases in Akt and endothelial NOS phosphorylated proteins in the aorta of septic animals. ATP reduces superoxide release resulting in an improved vasorelaxant response. Sepsis may uncouple NOS to produce superoxide. We showed that ATP through Akt pathway phosphorylated endothelial NOS and “re-couples” NOS function.

Evaluation of the chronic complications of diabetes in a high fructose diet in rats.

The increasing prevalence of type 2 diabetes is associated with increasing health costs, especially for the treatment of cardiovascular disease. The development of new treatment modalities requires animal models that mimic the range of pathophysiological changes seen in diabetic humans. Dietary fructose intake has been linked to the increase in insulin resistance as part of the metabolic syndrome; fructose-fed rats develop type 2 diabetes. This study has characterized the cardiovascular changes in young adult male Wistar rats fed a 61% fructose diet for 16 weeks. Our results extend the reported changes of hypertension, lipid abnormalities, impaired glucose tolerance and impaired oxidative defense to include ventricular dilatation with hypertrophy and decreased contractile function, together with increased inflammatory cell infiltration into the ventricular myocardium, resulting in excessive collagen deposition and an increased stiffness of the left ventricle. However, endothelial dysfunction, tactile allodynia as a symptom of peripheral neuropathy and retinopathy are not present in these rats, in contrast to the streptozotocin-induced model of type 1 diabetes. Thus, fructose feeding mimics many, but not all, of the symptoms of type 2 diabetes in humans.

Prevalência de mineralização aórtica detectada no abate de bovinos no estado de Minas Gerais, Brasil / Prevalence of aortic mineralization in slaughtered bovine from the state of Minas Gerais, Brazil

Descreve-se a prevalência da mineralização aórtica em bovinos abatidos em frigorífico de Belo Horizonte, MG. Foram examinados 783 fragmentos de aorta torácica de bovinos de diferentes grupos raciais, sexo e idades. As lesões foram caracterizadas em: grau I, grau II, grau III ou grau IV, baseado na intensidade das alterações macroscópicas. Duzentas e noventa e oito (38,1 por cento) aortas foram classificadas com algum tipo de lesão: 180 com grau I (23,0 por cento), 59 com grau II (7,5 por cento), 35 com grau III (4,5 por cento) e 24 com grau IV (3,1 por cento). Houve diferenças nas freqüências de mineralização aórtica quanto ao sexo, a idade e a raça. Fêmeas e machos castrados (54,6 por cento e 50,7 por cento, P<0,00001 e P<0,0001, respectivamente) comparados a machos inteiros (27,5 por cento), mestiços zebuínos de dupla aptidão e animais sem raça definida (59,3 por cento e 47,8 por cento, P<0,02 e P<0,05, respectivamente) comparados a zebus puros (37,4 por cento) e animais acima de três anos de idade (59,4 por cento, P<0,0001) comparados a animais com 2-3 anos ou menos de dois anos de idade (21,7 por cento e 13,9 por cento) foram mais freqüentemente acometidos por mineralização aórtica.

This study describes the prevalence of aortic mineralization in slaughtered bovine in the state of Minas Gerais. Fragments of thoracic aorta from 783 animals from different origin, breed, gender and age were evaluated macroscopically. All lesions were characterized and divided in, grade I, grade II, grade III and grade IV, depending on the severity of the lesions. A total of 298 (38.1 percent) aortas had lesions, as follow: 180 grade I (23.0 percent), 59 grade II (7.5 percent), 35 grade III (4.5 percent) and 24 grade IV (3.1 percent). Differences concerning age, breed and sex were observed. Females and castrated males (54.6 percent and 50.7 percent, P<0.00001 and P<0.0001, respectively) compared to intact males, zebu-crossbred and mixed bred (59.3 percent and 47.8 percent, P<0.02 and P<0.05, respectively) compared to pure zebu (37,4 percent) and animals older then 3 years (59.4 percent, P<0.0001) compared to animals 2-3 years or under 2 years of age (21.7 percent and 13.9 percent, respectively) were more frequently affected by aortic mineralization.

Efeito aterogênico da poluição atmosférica: associação aos anticorpos anti LDLox e anti peptídeo D da apoB e aos aspectos morfométricos e inflamatórios / Aterogenic effect of air pollution: association to anti-oxLDL and anti peptide D-ApoB and in aspects morphometric and inflamatory

O objetivo deste estudo foi identificar genes diferencialmente expressos entre adenocarcinoma de pâncreas de pacientes com e sem diabetes melito, utilizando microarranjos de oligonucleotídeos hibridizados com cRNA de tumores advindos de pacientes nessas duas condições. Observou-se nos microarranjos que 293 genes estavam pelo menos duas vezes mais expressos nos tumores dos pacientes com diabetes melito. Outros 297 genes estavam mais expressos nos tumores dos não-diabéticos...

The objective of the present study was to identify differentially expressed genes between pancreatic adenocarcinoma from patients who had and who did not have diabetes mellitus. Oligonucleotides bioarrays were hybridized with complementary RNA from tumors of two diabetic and two normotolerant patients. It was observed that 293 genes were at least twice more expressed in tumors from diabetic patients. Other 297 genes were more expressed in tumors from normotolerant patients. In quantitative RT-PCR performed in 12 tumors samples, FAM3D mRNA was more expressed in tumors from diabetic than in tumors from non-diabetic patients...