RESUMO
OBJECTIVE: Resilience is a complex, yet rather unexplored topic in patients with congenital heart disease (CHD). The goal of this study was to assess and compare resilience in children with CHD with healthy controls during the COVID-19 pandemic. DESIGN AND PATIENTS: From June 2020 to June 2021, 124 children with various CHDs (14.6±2.1 years, 49 girls) and 124 matched healthy controls (14.8±2.0 years, 49 girls) completed the Resilience Scale-11 short version. RESULTS: Resilience was significantly reduced in children with CHD compared with healthy controls (CHD: 59.0±10.0 vs healthy controls: 64.4±6.5, p<0.001). That reduction was prominent in all CHD subgroups except those with left heart obstruction (aortic stenosis and coarctation of the aorta) and patients with transposition of the great arteries. Complex CHD had the lowest resilience of 57.6±8.4 (p<0.001) after adjusting for age and sex according to group differences. There was no difference between native CHD and CHD with open-heart surgery (native: 59.5±12.2 vs surgery: 58.8±9.3, p=0.758). CONCLUSIONS: Resilience was reduced in children and adolescents with CHD compared with healthy peers during the COVID-19 pandemic. Children with complex severity appeared to be particularly affected. These findings emphasise continued efforts to provide a holistic and multidisciplinary approach in medical aftercare of these patients and their families.
Assuntos
Coartação Aórtica , COVID-19 , Cardiopatias Congênitas , Transposição dos Grandes Vasos , Feminino , Adolescente , Humanos , Criança , Pandemias , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/epidemiologia , COVID-19/epidemiologiaRESUMO
"Persistence of the fifth aortic arch" is a rare congenital cardiovascular anomaly that consists of an abnormal vessel arising from the distal ascending aorta connecting with the systemic or pulmonary circulation. We report a case of a type A interruption of the aortic arch and a coarctation of the fifth aortic arch, which connected the ascending with the descending aorta. No cardiac surgery was required because a covered stent was successfully implanted in the fifth aortic arch when the patient was 4 years old. A chromosome 9 q arm duplication of uncertain significance was also found, an anomaly never described before in this clinical context.
Assuntos
Aorta Torácica/diagnóstico por imagem , Coartação Aórtica/terapia , Tratamento Conservador/métodos , Coartação Aórtica/diagnóstico , Angiografia por Tomografia Computadorizada , Ecocardiografia , Humanos , Lactente , MasculinoRESUMO
BACKGROUND: We aimed to assess differences in myocardial deformation in fetuses at risk for coarctation (CoA) and the effects of maternal hyperoxygenation on deformation. METHODS: Fetal echocardiography and velocity vector imaging were performed prospectively and serially in 48 fetuses with a small aortic isthmus and 48 gestation age-matched normal fetuses. Fetuses with a small aortic isthmus were randomly divided into two groups: one group with and the other group without maternal supplemental oxygen administration. The strain (S) and strain rate (SR) in the left ventricle (LV) and right ventricle (RV) were measured and compared between the groups. Regression analyses were performed to identify potential factors associated with myocardial deformation. RESULTS: Compared with normal fetuses, fetuses with a small aortic isthmus exhibited a lower S and SR at baseline. A negative correlation was found between aortic isthmus velocity-time integrals and S and SR at baseline (P < .05). In the group that received supplemental oxygen therapy, the S and SR in both the LV and RV increased as a function of time, especially 4 weeks after the initiation of oxygen therapy (P < .05). The duration of oxygen therapy and increased combined cardiac index were associated with increased myocardial deformation (P < .05). CONCLUSIONS: Myocardial deformation appears abnormal in those at risk for CoA beginning in utero, and chronic oxygen therapy appears to increase deformation measures. These findings may improve patient counseling and perinatal management.
Assuntos
Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/etiologia , Ecocardiografia Doppler em Cores/métodos , Coração Fetal/diagnóstico por imagem , Oxigenoterapia Hiperbárica/efeitos adversos , Ultrassonografia Pré-Natal/métodos , Adulto , Feminino , Idade Gestacional , Humanos , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
We investigated the effect of ginsenoside Rb1 on cardiac function and remodeling in heart failure (HF). Four weeks after HF induction, the rats were administrated with ginsenoside Rb1 (35 and 70 mg/kg) and losartan (4.5 mg/kg) for 8 weeks. Losartan was used as a positive control. Cardiac function was assessed by measuring hemodynamic parameters. Histological changes were analyzed by HE and Masson's trichrome staining. Cardiac hypertrophy, fibrosis, mitochondrial membrane potential and glucose transporter type 4 (GLUT4) levels were evaluated. In the present study, high dose of (H-) ginsenoside Rb1 decreased heart rate, improved cardiac function and alleviated histological changes induced by HF. H-ginsenoside Rb1 attenuated cardiac hypertrophy and myocardial fibrosis by decreasing left ventricular (LV) weight/heart weight ratio and cardiomyocyte cross-sectional area and reducing the levels of atrial natriuretic factor (ANF), ß-myosin heavy chain (ß-MHC), periostin, collagen I, Angiotensin II (Ang II), Angiotensin converting enzyme (ACE) and Ang II type 1 (AT1) receptor. Moreover, H-ginsenoside Rb1 decreased mitochondrial membrane potential and enhanced the translocation of GLUT4 to plasma membrane. The TGF-ß1/Smad and ERK signaling pathways were inhibited and the Akt pathway was activated. These findings suggest that ginsenoside Rb1 might restore cardiac/mitochondrial function, increase glucose uptake and protect against cardiac remodeling via the TGF-ß1/Smad, ERK and Akt signaling pathways.
Assuntos
Ginsenosídeos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Fitoterapia , Remodelação Ventricular/efeitos dos fármacos , Animais , Coartação Aórtica , Fator Natriurético Atrial/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fibrose , Ginsenosídeos/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/prevenção & controle , Hipertrofia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Ratos Sprague-DawleyRESUMO
AIMS: Models of blood flow in the left ventricle (LV) and aorta are an important tool for analysing the interplay between LV deformation and flow patterns. Typically, image-based kinematic models describing endocardial motion are used as an input to blood flow simulations. While such models are suitable for analysing the hemodynamic status quo, they are limited in predicting the response to interventions that alter afterload conditions. Mechano-fluidic models using biophysically detailed electromechanical (EM) models have the potential to overcome this limitation, but are more costly to build and compute. We report our recent advancements in developing an automated workflow for the creation of such CFD ready kinematic models to serve as drivers of blood flow simulations. METHODS AND RESULTS: EM models of the LV and aortic root were created for four pediatric patients treated for either aortic coarctation or aortic valve disease. Using MRI, ECG and invasive pressure recordings, anatomy as well as electrophysiological, mechanical and circulatory model components were personalized. RESULTS: The implemented modeling pipeline was highly automated and allowed model construction and execution of simulations of a patient's heartbeat within 1 day. All models reproduced clinical data with acceptable accuracy. CONCLUSION: Using the developed modeling workflow, the use of EM LV models as driver of fluid flow simulations is becoming feasible. While EM models are costly to construct, they constitute an important and nontrivial step towards fully coupled electro-mechano-fluidic (EMF) models and show promise as a tool for predicting the response to interventions which affect afterload conditions.
Assuntos
Coartação Aórtica/fisiopatologia , Valva Aórtica/fisiopatologia , Doenças das Valvas Cardíacas/fisiopatologia , Hemodinâmica , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Função Ventricular Esquerda , Potenciais de Ação , Adolescente , Coartação Aórtica/diagnóstico , Coartação Aórtica/terapia , Automação , Fenômenos Biomecânicos , Cateterismo Cardíaco , Criança , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Frequência Cardíaca , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/terapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Modelos Anatômicos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , Resultado do Tratamento , Fluxo de TrabalhoRESUMO
The aim was to investigate the impact of maternal hyperoxygenation (HO) on cardiac dimensions in fetuses with isolated Coarctation (CoA). Fetal echocardiography was performed serially in 48 fetuses with CoA and gestation age matched normal fetues. The Z-scores for the mitral valve (MV), tricuspid valve (TV), aortic valve (AV), ascending aorta (AAo), isthmus, pulmonary valve (PV), main pulmonary artery (MPA), and descending aorta (DAo) were measured and compared among normal fetuses, CoA fetuses with oxygen and CoA fetuses with air. In the group with oxygen, 6 L/min oxygen was administered to the mother using a face mask. Regression analyses were performed to identify potential factors for HO outcome. The left heart dimension Z-scores increased gradually during HO therapy periods, especially at 4 weeks after oxygen therapy (P < 0.05). As for the case group with air, the left heart dimension remained unchanged. The duration of HO was associated with aortic arch Z-scores (adjusted R2 = 0.199, 0.60 for AAO and isthmus, respectively). Sustained maternal middle-flow oxygenation can be safely used to improve left heart dimensions in fetuses with isolated CoA. The duration of HO were associated with treatment outcome. These findings may provide useful information for developing novel treatment strategies.
Assuntos
Aorta Torácica/anatomia & histologia , Coartação Aórtica/patologia , Coartação Aórtica/terapia , Feto/anatomia & histologia , Coração/anatomia & histologia , Oxigenoterapia Hiperbárica , Troca Materno-Fetal , Adulto , Ecocardiografia , Feminino , Humanos , Gravidez , Resultado do TratamentoRESUMO
UNLABELLED: With a prevalence of 2.6-4.5 %, infantile haemangiomas (IH) represent the most common tumour of infancy. While the majority of IH does not require therapy and regresses spontaneously, about 10 % of IH exhibit complications such as obstruction, ulceration or disfigurement. With the advent of oral propranolol, many conventional treatment options have become obsolete. This paper summarizes current recommendations for management of complicated IH. These recommendations have been written by an expert group after a consensus process including bibliographic review, several drafts of synthesis, meetings with quantitative voting system and redaction of an approved final manuscript. CONCLUSION: Oral propranolol is the first-line agent for the treatment of complicated IH. WHAT IS KNOWN: ⢠Infantile haemangiomas (IH) are the most common tumours of infancy. Within a very short period after its discovery and long before the publication of randomized controlled trials, propranolol has become the number one agent for the treatment of complicated IH. What is New: ⢠We report IH treatment recommendations of an international, interdisciplinary team of experts, based on an up-to-date review of the literature.
Assuntos
Hemangioma/terapia , Administração Tópica , Antagonistas Adrenérgicos beta/uso terapêutico , Coartação Aórtica/complicações , Crioterapia , Diagnóstico Diferencial , Estética , Anormalidades do Olho/complicações , Glucocorticoides/uso terapêutico , Hemangioma/diagnóstico , Humanos , Imunossupressores/uso terapêutico , Lactente , Terapia a Laser , Síndromes Neurocutâneas/complicações , Fototerapia , Propranolol/uso terapêutico , Fatores de Risco , Sirolimo/uso terapêutico , Neoplasias Vasculares/diagnóstico , Conduta ExpectanteRESUMO
Aortic dilatation and aortic dissection are increasingly recognised in patients with Turner syndrome (TS). Risk factors for aortic dissection include aortic dilatation, bicuspid aortic valves, coarctation of aorta and pregnancy. The risk of death due to aortic dissection in pregnancy in TS is 2%, which is approximately 100 times higher than the general population, as maternal mortality is extremely low. Ongoing cardiovascular monitoring is recommended, although there remain several unanswered questions in relation to cardiovascular imaging especially the choice of modality for detection of vascular, valvular abnormalities and measurements of aortic dimensions. Due to the relative short stature of patients with TS, aortic dimensions need to be defined by aortic measurements adjusted for body surface area, known as aortic sized index (ASI). The relationship of ASI and other risk factors with aortic dissection is only beginning to be clarified. Clinical management and monitoring of such patients should be delivered by a group of clinicians familiar with the issues unique to TS patients in a multidisciplinary fashion. All clinicians including the non-specialists need to have a low threshold of suspecting aortic dissection in these adolescents and young adults. This up to date review, including a summary of all 122 published cases of TS patients with aortic dissection, aims to provide a summary of recent publications on characteristics of aortic dissection and aortic dilatation in TS to highlight gaps in knowledge and propose possible clinical monitoring pathway of cardiovascular health in children and adults with TS. Cardiovascular assessment and risk counselling is especially crucial during the period of transition of adolescents with TS, although life long monitoring by expert cognizant to the issues specific in TS is essential.
Assuntos
Aneurisma da Aorta Torácica/epidemiologia , Síndrome de Turner/epidemiologia , Síndrome de Turner/fisiopatologia , Adolescente , Adulto , Aneurisma Aórtico/epidemiologia , Aneurisma Aórtico/prevenção & controle , Coartação Aórtica/epidemiologia , Valva Aórtica/anormalidades , Doença da Válvula Aórtica Bicúspide , Feminino , Doenças das Valvas Cardíacas/epidemiologia , Humanos , Cariótipo , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Monitorização Fisiológica , Gravidez , Fatores de Risco , Síndrome de Turner/mortalidadeRESUMO
BACKGROUND: HMG-coA-reductase-inhibitors (statins) have been proven to reduce atherosclerosis progression as observed by carotid intima-media thickness in patients with known coronary heart disease, independent of lipid lowering. Cardiovascular complications are common in patients after successful coarctation repair. The effect of statins on cardiovascular risk in adults after successful coarctation repair has not yet been established. METHODS: We designed a multicentre, prospective, randomised, open label trial to evaluate the effect of the HMGcoA-reductase-inhibitor (Atorvastatin) on atherosclerotic progression in adult post-coarctectomy patients. The primary endpoint in this study is the carotid intima-media thickness as measured by Bmode ultrasonography of the carotid arteries. CONCLUSION: This large prospective, randomised, open label trial will establish the effect of HMG-coA-reductase inhibitors (Atorvastatin) on cardiovascular risk in adult patients after successful coarctation repair.
Assuntos
Coartação Aórtica/cirurgia , Aterosclerose/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos , Artérias Carótidas/diagnóstico por imagem , Ácidos Heptanoicos/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Cuidados Pós-Operatórios/métodos , Pirróis/administração & dosagem , Adulto , Coartação Aórtica/complicações , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Atorvastatina , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , História Antiga , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento , UltrassonografiaRESUMO
BACKGROUND: Aim of study is designed to investigate whether apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) expression is changed in abdominal aortic coarctation models. METHODS: Male Sprague-Dawley rats were randomly assigned with abdominal aortic coarctation, repaired group, sham, and control groups. Endothelial function was assessed with endothelium-dependent relaxations. Detection of superoxide anion and lipid peroxidation was performed by lucigenin chemiluminescence and thiobarbituric acid-reactive substances assay. APE1/Ref-1 expression was measured with Western blot and immunohistochemistry. RESULTS: In anesthetized condition, the abdominal aortic coarctation rats showed hypertension as systolic/diastolic arterial pressure of 171/114 mm Hg, compared with 114/94 mm Hg of control. Endothelium-dependent relaxations were significantly impaired in the aortic coarctation which was recovered in 1 week after coarctation repair. Superoxide production and lipid peroxidation were elevated in aortic coarctation rats. In immunohistochemistry, APE1/Ref-1 expressions were increased at aorta and kidney in aortic coarctation rats. Increased APE1/Ref-1 expression in aorta was recovered by repair of coarctation. CONCLUSIONS: Taken together, it suggests that APE1/Ref-1 expression was increased in aortic coarctation-induced hypertensive rats, suggesting a biomarker for hypertension. Impaired endothelium dependent relaxation in the aortic coarctation can be modulated by repair of coarctation or the modulation of blood pressure.
Assuntos
Animais , Humanos , Masculino , Ratos , Acridinas , Aorta , Coartação Aórtica , Pressão Arterial , Pressão Sanguínea , Western Blotting , Endotélio , Hipertensão , Imuno-Histoquímica , Rim , Peroxidação de Lipídeos , Luminescência , Oxirredução , Estresse Oxidativo , Ratos Sprague-Dawley , Relaxamento , Salicilamidas , SuperóxidosRESUMO
Ginsenoside Rg(1) (Rg(1)), one of the active components of Panax ginseng, has been reported to promote endogenous nitric oxide (NO) production in some tissues, and to inhibit left ventricular (LV) hypertrophy in rats. This study aimed to investigate whether Rg(1)-induced inhibition of rat LV hypertrophy is mediated by NO-production. Rat LV hypertrophy was induced by abdominal aorta coarctation. Rg(1) 15 mg/kg/d, L-arginine 200 mg/kg/d, and the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME) 100 mg/kg/d used with the same dose of L-arginine or Rg(1) were given starting from 1 d after surgery for 21 consecutive days. LV hypertrophy was evidenced by determining LV weight and mRNA expression of atrial natriuretic peptide, a marker of cardiac hypertrophic response, as well as by histopathology. Rg(1) and L-arginine administration significantly reduced the elevated LV hypertrophic parameters independent of LV systolic pressure changing, and ameliorated the histopathology of LV myocardium and LV diastolic function. All the beneficial effects of Rg(1) and L-arginine were abolished or blunted by L-NAME. Further to examine the role of NO in Rg(1) inhibition on LV hypertrophy, expression of endothelial NOS was determined at the transcript levels. In our experimental conditions endothelial NOS mRNA expression in LV tissue was lowered by abdominal aorta coarctation, and upregulated by Rg(1) administration. These results demonstrate that Rg(1)-induced protection against LV hypertrophy elicited by abdominal aorta coarctation in rats is mediated, at least in part, via endogenous NO production and release.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Ginsenosídeos/uso terapêutico , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Óxido Nítrico/biossíntese , Panax/química , Fitoterapia , Abdome/irrigação sanguínea , Animais , Coartação Aórtica , Arginina/farmacologia , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Fármacos Cardiovasculares/farmacologia , Modelos Animais de Doenças , Endotélio/enzimologia , Ginsenosídeos/farmacologia , Ventrículos do Coração/patologia , Masculino , Miocárdio/patologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Tamanho do Órgão , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Clark (1996) proposed that abnormal blood flow is related to some congenital cardiovascular malformations (CCVMs), particularly CCVM with obstruction to blood flow. Our hypothesis is that CCVMs may relate to genes that affect blood coagulation or flow. We studied whether polymorphisms of such genes are related to CCVMs; previous association of these SNPs to conotruncal CCVMs is described. METHODS: We assessed risk of pulmonary stenosis (PS, N = 120), atrial septal defect (ASD, N = 108), aortic stenosis (AS, N = 36), and coarctation of the aorta (CoAo, N = 64), associated with 33 candidate genes, selected for their relationship to blood flow affected by homocysteine metabolism, coagulation, cell-cell interaction, inflammation, or blood pressure regulation. RESULTS: Effects were specific to cardiac phenotype and race. CoAo was associated with MTHFR (-667) C>T (odds ratio [OR] for TT 3.5, 95% confidence limits [CI] 1.4-8.6). AS was associated with a polymorphism of SERPINE1, G5>G4, OR = 5.6 for the homozygote with 95% CI 1.4-22.9. Unique polymorphisms were associated with increased risk of ASD and PS: NPPA 664G>A with ASD (OR of 2.4, 95%CI 1.3-4.4) and NOS3 (-690) C>T with PS (OR 6.1; 95% CI 1.6-22.6 in the African American population only). For ASD, the NPPA (-664) G>A SNP there was increased risk from the variant genotype only in maternal smokers (OR 2.6; 95% CI 1.0-7.2). CONCLUSIONS: Genes affecting vascular function and coagulation appear to be promising candidates for the etiology of cardiac malformations and warrant further study.
Assuntos
Cardiopatias Congênitas/genética , Polimorfismo de Nucleotídeo Único , Coartação Aórtica/genética , Estenose da Valva Aórtica/genética , Coagulação Sanguínea/genética , Pressão Sanguínea/genética , Pressão Sanguínea/fisiologia , Comunicação Celular/genética , Suplementos Nutricionais , Feminino , Comunicação Interatrial/genética , Homocisteína/genética , Homocisteína/metabolismo , Humanos , Recém-Nascido , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Gravidez , Estudos Prospectivos , Estenose da Valva Pulmonar/genética , Grupos Raciais/genéticaAssuntos
Coartação Aórtica/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Quilotórax/terapia , Nutrição Parenteral/métodos , Adolescente , Criança , Quilotórax/sangue , Quilotórax/etiologia , Quilotórax/metabolismo , Metabolismo Energético , Humanos , Masculino , Resultado do TratamentoRESUMO
Since angiotensin (Ang) (1-7) injected into the brain blocked Ang II pressor actions in rats made hypertensive by aortic coarctation (CH), we examined systemic and tissue angiotensin peptide levels, specifically concentrating on the hypothalamic Ang-(1-7) levels. Plasma, heart and kidney isolated from CH rats showed increased levels of Ang I, Ang II and Ang-(1-7) compared with the normotensive group, with Ang II being the predominant peptide in heart and kidney. In the hypothalamus, equimolar amounts of Ang II and Ang-(1-7) were found in the sham group, whereas only Ang-(1-7) levels increased in CH rats. We conclude that aortic coarctation activates systemic and tissue renin-angiotensin system. The increased central levels of Ang-(1-7) in the CH rats suggest a potential mitigating role of this peptide in central control of the hypertensive process.
Assuntos
Angiotensina I/metabolismo , Coartação Aórtica/complicações , Coartação Aórtica/metabolismo , Hipertensão/etiologia , Hipertensão/metabolismo , Hipotálamo/metabolismo , Fragmentos de Peptídeos/metabolismo , Angiotensina II/metabolismo , Angiotensinas/metabolismo , Animais , Rim/metabolismo , Masculino , Miocárdio/metabolismo , Ratos , Ratos Wistar , Sistema Renina-Angiotensina/fisiologiaRESUMO
The aim of the present work was to study the central and plasma pharmacokinetics of irbesartan (IRB) and its possible hypothalamic antihypertensive effect in sham-operated (SO) and aortic-coarctated (ACo) rats at a chronic hypertensive stage using the microdialysis technique. Anesthetized Wistar rats were used 42 days after ACo or SO. For the study of plasma pharmacokinetics, a vascular shunt probe was inserted into the carotid artery. In a separated experiment, a concentric probe was placed into the anterior hypothalamus for the study of IRB distribution in the central nervous system. Based on the hypothalamic concentrations of IRB reached in ACo rats, the anterior hypothalamus of SO and ACo animals was perfused with a Ringer solution containing approximately 6 microg x ml(-1) of the drug. IRB (10 mg x kg(-1) i.v.) induced a late decrease of heart rate (HR) in ACo animals (DeltaHR: -42 +/- 10 bpm, n = 5, p < 0.05 vs. SO rats) but not in SO rats (DeltaHR: 11 +/- 13 bpm, n = 5). Systemic administration of the drug reduced the mean arterial pressure (MAP) of both experimental groups, but the hypotensive effect was greater in ACo (DeltaMAP: -39.9 +/- 5.0 mm Hg, n = 5, p < 0.05 vs. SO rats) than in SO rats (DeltaMAP: -25.4 +/- 2.1 mm Hg, n = 5). A similar pharmacokinetic profile was observed in both experimental groups. Hypothalamic distribution of IRB was greater in ACo (AUC: 730 +/- 130 ng x ml(-1) h(-1), n = 5, p < 0.05 vs. SO rats) than in SO animals (AUC: 283 +/- 87 ng x ml(-1) h(-1), n = 5). The IRB hypothalamic perfusion induced an antihypertensive effect in ACo (DeltaMAP: -15.1 +/- 1.0 mm Hg, n = 5, p < 0.05 vs. Ringer perfusion) but not in SO rats. In conclusion, the chronic aortic coarctation did not modify the plasma pharmacokinetics of IRB, but it increased the distribution of the drug in the central nervous system. The greater hypotensive effect of IRB observed in ACo animals suggests the involvement of AT1 receptors in the maintenance of the hypertensive stage in chronic ACo rats. The hypotensive effect of IRB in ACo animals could be explained, at least in part, due an action on the anterior hypothalamic angiotensin system.
Assuntos
Anti-Hipertensivos/administração & dosagem , Coartação Aórtica/tratamento farmacológico , Compostos de Bifenilo/administração & dosagem , Hipotálamo/efeitos dos fármacos , Tetrazóis/administração & dosagem , Animais , Anti-Hipertensivos/metabolismo , Coartação Aórtica/metabolismo , Coartação Aórtica/fisiopatologia , Compostos de Bifenilo/metabolismo , Doença Crônica , Feminino , Hipotálamo/metabolismo , Irbesartana , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Ratos , Ratos Wistar , Tetrazóis/metabolismoRESUMO
Since it has been suggested that angiotensin (Ang) (1-7) functions as an antihypertensive peptide, we studied its effect on the Ang II-enhanced norepinephrine (NE) release evoked by K+ in hypothalami isolated from aortic coarcted hypertensive (CH) rats. The endogenous NE stores were labeled by incubation of the tissues with 3H-NE during 30 min, and after 90 min of washing, they were incubated in Krebs solution containing 25 mM KCl in the absence or presence of the peptides. Ang-(1-7) not only diminished the K+-evoked NE release from hypothalami of CH rats, but also blocked the Ang II-enhanced NE release induced by K+. Ang-(1-7) blocking action on the Ang II response was prevented by [D-Ala7]Ang-(1-7), an Ang-(1-7) specific antagonist, by PD 123319, an AT2-receptor antagonist, and by Hoe 140, a B2 receptor antagonist. Ang-(1-7) inhibitory effect on the Ang II facilitatory effect on K+-stimulated NE release disappeared in the presence of Nomega-nitro-L-arginine methylester and was restored by L-arginine. Our present results suggest that Ang-(1-7) may contribute to blood pressure regulation by blocking Ang II actions on NE release at the central level. This inhibitory effect is a nitric oxide-mediated mechanism involving AT2 receptors and/or Ang-(1-7) specific receptors and local bradykinin generation.
Assuntos
Angiotensina II/análogos & derivados , Angiotensina II/farmacologia , Angiotensina I/farmacologia , Anti-Hipertensivos/farmacologia , Bradicinina/análogos & derivados , Hipertensão/fisiopatologia , Hipotálamo/efeitos dos fármacos , Norepinefrina/antagonistas & inibidores , Fragmentos de Peptídeos/farmacologia , Angiotensina I/antagonistas & inibidores , Angiotensina II/antagonistas & inibidores , Animais , Anti-Hipertensivos/antagonistas & inibidores , Coartação Aórtica/complicações , Bradicinina/farmacologia , Hipertensão/etiologia , Hipotálamo/metabolismo , Imidazóis/farmacologia , Técnicas In Vitro , Óxido Nítrico/metabolismo , Norepinefrina/metabolismo , Fragmentos de Peptídeos/antagonistas & inibidores , Potássio/farmacologia , Piridinas/farmacologia , Ratos , Ratos WistarRESUMO
A 14-year-old boy with coarctation of the aorta who showed repeat ventricular fibrillation during anesthesia, and ultimately sudden cardiac death in school, is presented. Electrocardiography showed J waves in the left precordial leads, which became prominent after an episode of ventricular fibrillation. While some of the clinical features and electrophysiological findings were similar to those seen in Brugada syndrome, others were inconsistent. J waves in the left precordial leads should be recognized as a possible waveform change inducing ventricular fibrillation predominantly at rest.
Assuntos
Anestesia Geral , Coartação Aórtica/complicações , Coartação Aórtica/terapia , Eletrocardiografia , Sistema de Condução Cardíaco/patologia , Sistema de Condução Cardíaco/cirurgia , Fibrilação Ventricular/complicações , Fibrilação Ventricular/terapia , Adolescente , Coartação Aórtica/diagnóstico , Morte Súbita Cardíaca/etiologia , Desfibriladores Implantáveis , Técnicas Eletrofisiológicas Cardíacas , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Masculino , Fibrilação Ventricular/diagnósticoRESUMO
A aortoplastia trapezoidal é uma variação da técnica término-terminal que se ampara em elementos de geometria, objetivando aumentar o diâmetro da aorta ao nível da anastomose e minimizar o aparecimento de gradientes residuais ou recorrentes. Foi aplicada em um grupo de 33 pacientes, sendo a maioria do sexo masculino (22/66,7%); a idade variou de zero a 36 anos (m 9,5 ± 9,7), não tendo ocorrido complicações significantes na cirurgia e no pós-operatório. O tempo de evolução em longo prazo variou de um ano e um mês a 7,6 anos (m 3,6 ± 3,4) e foi possível constatar supressão dos sintomas, normalização da pressão arterial e suspensão da terapêutica anti-hipertensiva na maioria dos pacientes (p < 0,0001). Constatou-se, também, importante redução dos gradientes pressóricos observados ao ecocardiograma/Doppler e ao cateterismo cardíaco (p < 0,001). A análise das aortografias obtidas no estudo hemodinâmico e na ressonância magnética mostrou boa continuidade anatômica, assim como o estudo morfométrico da aorta revelou efeitos benéficos da operação traduzidos pelo aumento de calibre do segmento distal do arco, istmo e porção descendente. A despeito de boa evolução clínica, a ocorrência de hipoplasia ístmica não tratada foi a responsável pela detecção de gradientes e estenoses maiores em dois casos. Não ocorreu mortalidade precoce ou tardia na série, e a análise estatística das correlações entre os métodos invasivos e não invasivos empregados não mostrou boa correlação.
Assuntos
Gravidez , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Anastomose Cirúrgica/métodos , Angiografia por Ressonância Magnética/métodos , Cateterismo Cardíaco/métodos , Coartação Aórtica/cirurgia , Ecocardiografia Doppler/métodos , Evolução ClínicaRESUMO
A pharmacokinetic-pharmacodynamic study of methyldopa (MD) was made in anesthetized sham operated (SO) and aortic coarctated (ACo) rats by using a vascular shunt probe for arterial microdialysis and simultaneous blood pressure recording. Anesthetized Wistar rats were used 7 days after aortic coarctation or sham operation. A vascular shunt probe was inserted into the carotid artery and a concentric probe was placed into the striatum or posterior hypothalamus. MD and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the dialysates by HPLC-EC. MD (50 mg kg(-1)i.p.) induced an increase of heart rate in SO (Delta HR: 108 +/- 22 bpm, n= 6) and in ACo rats (Delta HR: 55 +/- 10 bpm, n= 6, P< 0.05, one way ANOVA). Moreover, MD also reduced the mean arterial pressure (MAP) of SO rats (Delta MAP: -10 +/- 4 mmHg, n= 6) and ACo animals (Delta MAP: -51 +/- 9 mmHg, n= 6, P< 0.05, one way ANOVA). Analysis of the arterial blood dialysates showed a lower half-life of MD in ACo rats (t(1/2): 1.5 +/- 0.3 h, n= 6, P< 0.05, 't' test) than in SO rats (t(1/2): 3.7 +/- 1.0 h, n= 6). A low accumulation and a fast decay of striatal MD levels were seen in ACo rats. However, peak levels of drug were greater in the hypothalamic dialysates of ACo rats than in SO animals samples. On the other hand, MD also induced an increase of DOPAC levels in the hypothalamic dialysates of ACo rats. In conclusion, the aortic coarctation modifies the pharmacokinetic and cardiovascular effect of MD in the rat. The action of this drug on dopaminergic neurotransmission is also altered in the ACo animals.
Assuntos
Anti-Hipertensivos/farmacocinética , Coartação Aórtica/metabolismo , Metildopa/farmacocinética , Microdiálise , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Anti-Hipertensivos/farmacologia , Coartação Aórtica/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Soluções para Diálise/farmacocinética , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Metildopa/administração & dosagem , Metildopa/farmacologia , Microdiálise/métodos , Ratos , Ratos WistarRESUMO
La coartación aórtica es una de las causas de hipertensión arterial corregible quirúrgicamente. En más del 65 por ciento de los casos el diagnóstico se realiza con el examen físico y la radiografía de tórax. A pesar de ello, transcurren habitualmente de 10 a 33 años entre la pesqisa del soplo; el desarrollo de la hipertensión arterial; el establecimiento del diagnóstico y la corrección quirúrgica de la malformación. En esta circunstancia generalmente ha existido una insuficiente valoración del cuadro clínico y el examen físico