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Objectives: We analyzed the impact of postoperative necrotizing enterocolitis (NEC) after cardiac surgery in neonatal age on neurodevelopmental (ND) outcome at 1 year of age. Methods: Using data from the Swiss Neurodevelopmental Outcome Registry for Children with Congenital Heart Disease (ORCHID), we analyzed perioperative variables including postoperative NEC (Bell's stage ≥2) and 1-year ND outcome (Bayley III). Results: The included patients (n = 101) had congenital heart disease (CHD), categorized as follows: 77 underwent biventricular repair for CHD with two functional chambers, 22 underwent staged palliation until the Fontan procedure for CHD with single ventricle physiology (n = 22), or 4 underwent single ventricle palliation or biventricular repair for borderline CHD (n = 4). Neonatal cardiopulmonary bypass (CBP) surgery was performed at a median age (IQR) of 8 (6) days. NEC occurred in 16 patients. Intensive care unit (ICU) length of stay (LOS) and the total duration of the hospitalization were longer in children with NEC than those in others (14 with vs. 8 days without NEC, p < 0.05; 49 with vs. 32 days without NEC, p < 0.05). The Bayley III scores of the analyzed patients determined at an age of 11.5 ± 1.5 months showed cognitive (CCS) (102.2 ± 15.0) and language scores (LCS) (93.8 ± 13.1) in the normal range and motor composite scores (MCS) (88.7 ± 15.9) in the low-normal range. After adjusting for socioeconomic status and CHD type, patients with NEC had lower CCS scores [ß = -11.2 (SE 5.6), p = 0.049]. Using a cumulative risk score including NEC, we found a higher risk score to be associated with both lower CCS [ß = -2.8 (SE 1.3), p = 0.030] and lower MCS [ßâ =â -3.20 (SE 1.3), p = 0.016]. Conclusions: Postoperative NEC is associated with longer ICU and hospital LOS and contributes together with other complications to impaired ND outcome at 1 year of age. In the future, national and international patient registries may provide the opportunity to analyze large cohorts and better identify the impact of modifiable perioperative risk factors on ND outcome. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT05996211.
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INTRODUCTION: Congenital heart disease (CHD) is the most frequent birth defect. As survival has significantly improved, attention has turned to neurodevelopmental outcomes of children undergoing heart surgery in early infancy. Since multiple risk factors contribute to neurodevelopmental alterations, a nationwide registry collecting data on medical characteristics, interventions, clinical course and neurodevelopment until school-age is needed to improve the quality of management, identify risk- and protective factors affecting neurodevelopment, and facilitate multicentre trials. METHODS AND ANALYSIS: The Swiss Outcome Registry for CHIldren with severe congenital heart Disease (ORCHID) is a nationwide, prospective, population-based patient registry developed (1) to collect baseline characteristics and clinical data of CHD patients operated with bypass-surgery or hybrid procedures in the first 6 weeks of life in Switzerland, (2) to monitor long-term neurodevelopment, and (3) to relate clinical characteristics and neurodevelopment to identify risk and protective factors in these children. This registry started data collection relating to pregnancy, birth, preoperative course, catheter-based and surgical treatment, postoperative course and reinterventions in 2019. The primary outcome includes standardised neurodevelopmental assessments at 9 to 12 months, 18 to 24 months and 5.5 to 6 years. We expect to include 80 to 100 children per year. Correlation and regression analyses will be used to investigate risk- and protective factors influencing neurodevelopment. ETHICS AND DISSEMINATION OF RESULTS: Swiss ORCHID received support by the Accentus Charitable Foundation, the Anna Mueller Grocholoski Stiftung, the Swiss Society of Paediatric Cardiology, the Verein Kinderherzforschung, and the Corelina - Stiftung für das Kinderherz, and was approved by the cantonal ethics committees. Findings will be presented at national and international scientific meetings, and published in peer-reviewed journals. Results will also be shared with patient organizations, primary health care providers, and public health stakeholders to ensure a widespread dissemination of the results.
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Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Desenvolvimento Infantil , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Gravidez , Estudos Prospectivos , Sistema de RegistrosRESUMO
BACKGROUND: Sternal closure by absorbable suture material is an established method for chest closure in pediatric cardiac surgical procedures. However, the formation of granuloma around knotted suture material is frequently observed and has potential for prolonged wound healing and infection, particularly in newborns and infants. This retrospective study analyzed the suitability and reliability of a novel absorbable, self-locking, multianchor knotless suture with antibacterial technology for sternal closure in pediatric cardiac surgical procedures. METHODS: The applied material (STRATAFIX Symmetric PDS Plus, Ethicon) presents a polydioxanon (PD) suture with a self-locking, multianchor design that enables a sternal closure in a continuous knotless suture technique. All children undergoing knotless closure after standard median sternotomy were examined for the occurrence of sternal wound infection or sternal instability by applying the screening criteria of the Centers for Disease Control and Prevention at hospital discharge and at 30 and 60 days. RESULTS: The new knotless sternal closure was used in 130 patients. Patients were a mean age of 19.0 ± 31.9 months (range, 0-142 months), and mean bodyweight was 7.8 ± 6.6 kg (range, 2.4-35 kg). Delayed sternal closure occurred in 23 patients, with a mean closure time after 2.9 ± 2.6 days. One superficial incisional sternal site infection occurred, but no cases of deep sternal site infection or sternal instability were observed. CONCLUSIONS: The application of the absorbable, knotless suture technique provides excellent results regarding the rate of sternal wound infection and improved healing after median sternotomy in pediatric patients.
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Procedimentos Cirúrgicos Cardíacos , Esterno , Lactente , Humanos , Recém-Nascido , Criança , Pré-Escolar , Estudos Retrospectivos , Reprodutibilidade dos Testes , Esterno/cirurgia , Esternotomia/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Suturas , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/cirurgia , Técnicas de Sutura , Antibacterianos , Resultado do TratamentoRESUMO
AIM OF STUDY: To report our experience of late correction after infancy in patients with tetralogy of Fallot (ToF). METHODS: Observational single-centre retrospective analysis of the surgical techniques and perioperative development of patients from developing countries undergoing total surgical correction of ToF after infancy, between 1 November 2011 and 30 November 2016. Variables are presented as numbers with percentages or as mean ± standard deviation. Due to the setting of the humanitarian programme, clinical and echocardiographic follow-up procedures could be conducted for only one month postoperatively. RESULTS: Twenty-five children (mean age: 70.8 ± 42 months, range 23-163; 44% female) underwent total surgical correction of ToF. Two patients (0.8%) initially received a Blalock-Taussig shunt and underwent subsequent correction 24 and 108 months later, respectively. Preoperative mean right ventricular/pulmonary artery (RV/PA) gradient was 84 ± 32 mm Hg, with a Nakata index of 164 ± 71 mm2/m2. Major aortopulmonary collateral arteries (MAPCAs) were observed in eight children (32%), six (26%) of whom underwent transcatheter closure before surgery. 24 children (96%) underwent a valve-sparing pulmonary valve repair and one patient received a transannular patch (TAP). There were no cases which saw major adverse cardiac and cerebrovascular events (MACCE). Mean duration of mechanical ventilation was 28 ± 19.6 hours (range 7-76). Pre-discharge echocardiography demonstrated a mean RV/PA gradient of 25 ± 5.7 mm Hg, with left ventricular ejection fraction >60% in all cases. Overall length of hospital stay was 11.7 ± 4.5 days. There were no in-hospital mortality cases. CONCLUSIONS: Late surgical correction of ToF can be safely performed and produce highly satisfying early postoperative results comparable to those of classical “timely” correction. A valve-sparing technique can be applied in the majority of children.
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Procedimentos Cirúrgicos Cardíacos , Artéria Pulmonar/fisiopatologia , Reoperação/estatística & dados numéricos , Tetralogia de Fallot/cirurgia , Pré-Escolar , Ecocardiografia , Feminino , Humanos , Masculino , Estudos RetrospectivosAssuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Matriz Extracelular/transplante , Migração de Corpo Estranho/patologia , Cardiopatias Congênitas/cirurgia , Mucosa Intestinal/transplante , Intestino Delgado/transplante , Adulto , Animais , Biópsia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Pré-Escolar , Matriz Extracelular/patologia , Feminino , Migração de Corpo Estranho/etiologia , Migração de Corpo Estranho/cirurgia , Xenoenxertos , Humanos , Recém-Nascido , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Masculino , Reoperação , Estudos Retrospectivos , Sus scrofa , Fatores de Tempo , Falha de TratamentoRESUMO
Purpose of this study was to investigate a potential correlation between the pattern of cerebral veins (CV) on susceptibility-weighted imaging (SWI) and blood oxygen saturation, as well as preoperative brain injury, in neonates with transposition of the great arteries (TGA). Eleven neonates with TGA underwent MRI preoperatively, including SWI, T1- and T2-weighted scans. Images were retrospectively evaluated and appearance of CV was graded from 0 (normal appearance) to 3 (severe prominent appearance). White matter injuries (WMI) and strokes were analysed. Results were correlated with preductal arterial oxygen saturation. As findings one subject showed a normal CV appearance (grade 0) whereas 10 showed pathological prominent CV (grades 1-3); median 2. Mean oxygen saturation ranged between 67.5% and 89.0% (median 81.0%). CV grade and mean oxygen saturation correlated significantly (p = 0.011). WMI were absent in 5 cases, mild in 4, and moderate in 2 cases. We conclude, that SWI has the potential to be used to estimate the current hypoxic burden on brain tissue in TGA newborns by assessing the prominence of the CV.
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Encéfalo/patologia , Veias Cerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Oxigênio/sangue , Transposição dos Grandes Vasos/sangue , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Hipóxia Celular , Estudos de Viabilidade , Feminino , Hemoglobinas/análise , Humanos , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Transposição dos Grandes Vasos/diagnóstico por imagem , Transposição dos Grandes Vasos/patologia , Transposição dos Grandes Vasos/cirurgiaRESUMO
We report the intraoperative courses of 2 consecutive Berlin Heart Excor® Pediatric Ventricular Assist Device implantations, in which transcranial Doppler ultrasonography helped to detect macroscopically undetected residual air bubbles captured in the pump after air removal had been correctly performed according to manufacturer's specifications. Our experience with these cases suggests that a beat-to beat deairing maneuver guided by transcranial Doppler is a useful strategy for reducing cerebral exposure to perioperative gaseous microembolism.
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Coração Auxiliar , Ultrassonografia Doppler Transcraniana/métodos , Ponte Cardiopulmonar/métodos , Embolia Aérea/diagnóstico , Embolia Aérea/prevenção & controle , Oxigenação por Membrana Extracorpórea , Humanos , Recém-Nascido , Período Intraoperatório , Masculino , GêmeosRESUMO
The cor triatriatum sinister is an uncommon congenital cardiac anomaly and reports in the literature are limited. It is often associated with other cardiac malformations, such as atrial septal defect, transposition of the great arteries, tetralogy of Fallot or atrioventricular septal defect. We present here a 6-year old boy who was diagnosed with cor triatriatum sinister, initially showing symptoms similar to mitral valve stenosis and congestive heart failure, and who underwent subsequent surgical correction using a left atrial approach. The fibromuscular membrane, separating the pulmonary veins from the mitral valve, was completely resected and postoperative echocardiography showed unobstructed pulmonary venous flow.
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Coração Triatriado , Parada Cardíaca Induzida , Átrios do Coração , Insuficiência Cardíaca/diagnóstico , Hipertensão Pulmonar , Estenose da Valva Mitral/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Veias Pulmonares , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Criança , Coração Triatriado/diagnóstico , Coração Triatriado/fisiopatologia , Coração Triatriado/cirurgia , Ecocardiografia Transesofagiana/métodos , Parada Cardíaca Induzida/efeitos adversos , Parada Cardíaca Induzida/métodos , Átrios do Coração/anormalidades , Átrios do Coração/cirurgia , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/prevenção & controle , Cuidados Intraoperatórios/métodos , Masculino , Veias Pulmonares/anormalidades , Veias Pulmonares/cirurgia , Risco Ajustado , Esternotomia/efeitos adversos , Esternotomia/métodos , Resultado do TratamentoRESUMO
Dilatation of the ascending aorta is an important sequel in conotruncal anomalies, such as tetralogy of Fallot (TOF) or d-transposition of the great arteries (TGA). We measured dimensions and their progression at different levels of the ascending aorta in 80 patients. In TOF patients, mean z-score for aortic annulus was 1.65 (range -3.16-6.47), for sinus 1.93 (range -2.28-5.39), for st-junction 4.15 (range 0.0-8.18), and for ascending aorta 3.51 (range -1.23-6.36). Over time, annulus z-scores increased in the univariate analysis [0.07/year, 95 % confidence interval (CI) 0.01-0.14; p = 0.02], and this was unique to male patients (0.08/year, 95 % CI 0.00-0.15; p = 0.05). z-scores of the ascending aorta decreased (-0.1/year, 95 % CI -0.18 to -0.02; p = 0.02), and this was confined to patients without aortic regurgitation (AR; -0.09/year, 95 % CI -0.18 to -0.01; p = 0.04). In TGA, mean z-score for the aortic annulus was 2.13 (range -3.71-8.39), for sinus 1.77 (range -3.04-6.69), for st-junction 1.01 (range -5.44-6.71), and for ascending aorta 0.82 (range -4.91-6.46). In bivariate analysis, annulus z-scores decreased in females (-0.14/year, 95 % CI -0.25 to -0.03; p = 0.01) and in patients without AR (-0.07/year, 95 % CI -0.14-0.0; p = 0.03). z-scores of the ascending aorta increased significantly in males (0.08/year, 95 % CI 0.0 to 0.16; p = 0.05) and in patients with AR (0.12/year, 95 % CI 0.03-0.21; p = 0.01). In conclusion, TOF and TGA z-scores of the ascending aorta differ significantly from those of the normal population. Progression of z-scores over time is influenced by diagnosis, sex, and presence of AR.
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Aorta/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Adolescente , Aorta/fisiopatologia , Valva Aórtica/fisiopatologia , Criança , Pré-Escolar , Dilatação Patológica , Ecocardiografia , Feminino , Cardiopatias Congênitas/complicações , Humanos , Lactente , Masculino , Suíça , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to evaluate right ventricular (RV) and left ventricular function and pulmonary circulation in chronic mountain sickness (CMS) patients with rest and stress echocardiography compared with healthy high-altitude (HA) dwellers. BACKGROUND: CMS or Monge's disease is defined by excessive erythrocytosis (hemoglobin >21 g/dl in males, 19 g/dl in females) and severe hypoxemia. In some cases, a moderate or severe increase in pulmonary pressure is present, suggesting a similar pathogenesis of pulmonary hypertension. METHODS: In La Paz (Bolivia, 3,600 m sea level), 46 CMS patients and 40 HA dwellers of similar age were evaluated at rest and during semisupine bicycle exercise. Pulmonary artery pressure (PAP), pulmonary vascular resistance, and cardiac function were estimated by Doppler echocardiography. RESULTS: Compared with HA dwellers, CMS patients showed RV dilation at rest (RV mid diameter: 36 ± 5 mm vs. 32 ± 4 mm, CMS vs. HA, p = 0.001) and reduced RV fractional area change both at rest (35 ± 9% vs. 43 ± 9%, p = 0.002) and during exercise (36 ± 9% vs. 43 ± 8%, CMS vs. HA, p = 0.005). The RV systolic longitudinal function (RV-S') decreased in CMS patients, whereas it increased in the control patients (p < 0.0001) at peak stress. The RV end-systolic pressure-area relationship, a load independent surrogate of RV contractility, was similar in CMS patients and HA dwellers with a significant increase in systolic PAP and pulmonary vascular resistance in CMS patients (systolic PAP: 50 ± 12 mm Hg vs. 38 ± 8 mm Hg, CMS vs. HA, p < 0.0001; pulmonary vascular resistance: 2.9 ± 1 mm Hg/min/l vs. 2.2 ± 1 mm Hg/min/l, p = 0.03). Both groups showed comparable systolic and diastolic left ventricular function both at rest and during stress. CONCLUSIONS: Comparable RV contractile reserve in CMS and HA suggests that the lower resting values of RV function in CMS may represent a physiological adaptation to chronic hypoxic conditions rather than impaired RV function. (Chronic Mountain Sickness, Systemic Vascular Function [CMS]; NCT01182792).
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Doença da Altitude/diagnóstico por imagem , Ecocardiografia Doppler , Ecocardiografia sob Estresse , Exercício Físico , Hipertensão Pulmonar/diagnóstico por imagem , Contração Miocárdica , Função Ventricular Direita , Aclimatação , Adulto , Altitude , Doença da Altitude/fisiopatologia , Pressão Arterial , Bolívia , Doença Crônica , Teste de Esforço , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Circulação Pulmonar , Suíça , Resistência Vascular , Função Ventricular EsquerdaRESUMO
Cardiac fibromas are extremely rare in the general pediatric population and may present with a wide spectrum of clinical signs, including life-threatening arrhythmias and sudden death. We report a 14-month-old boy who presented with failure to thrive as the only symptom. Echocardiography showed a large cardiac fibroma in the right ventricle. Cardiac magnetic resonance imaging confirmed the diagnosis. After complete surgical tumor resection, the boy showed normal catch-up growth. This case underlines the diversity of clinical features of cardiac tumors, which implies that they should be considered early in the differential diagnosis of infants with failure to thrive.
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Insuficiência de Crescimento/etiologia , Fibroma/complicações , Neoplasias Cardíacas/complicações , Ecocardiografia , Fibroma/diagnóstico por imagem , Fibroma/patologia , Fibroma/cirurgia , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Lactente , MasculinoRESUMO
BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem characterized by exaggerated hypoxemia and erythrocytosis. In more advanced stages, patients with CMS often present with functional and structural changes of the pulmonary circulation, but there is little information on the systemic circulation. In patients with diseases associated with chronic hypoxemia at low altitude, systemic vascular function is altered. We hypothesized that patients with CMS have systemic vascular dysfunction that may predispose them to increased systemic cardiovascular morbidity. METHODS: To test this hypothesis, we assessed systemic endothelial function (by flow-mediated dilation [FMD]), arterial stiffness, and carotid intima-media thickness and arterial oxygen saturation (Sao(2)) in 23 patients with CMS without additional classic cardiovascular risk factors and 27 age-matched healthy mountain dwellers born and permanently living at 3,600 m. For some analyses, subjects were classified according to baseline Sao(2) quartiles; FMD of the highest quartile subgroup (Sao(2) ≥ 90%) was used as a reference value for post hoc comparisons. RESULTS: Patients with CMS had marked systemic vascular dysfunction as evidenced by impaired FMD (CMS, 4.6% ± 1.2%; control subjects, 7.6% ± 1.9%; P < .0001), greater pulse wave velocity (10.6 ± 2.1 m/s vs 8.4 ± 1.0 m/s, P < .001), and greater carotid intima-media thickness (690 ± 120 µm vs 570 ± 110 µm, P = .001). A positive relationship existed between Sao(2) and FMD (r = 0.62, P < .0001). Oxygen inhalation improved (P < .001) but did not normalize FMD in patients with CMS, although it normalized FMD in hypoxemic control subjects (Sao(2) < 90%) and had no detectable effect in normoxemic control subjects (Sao(2) ≥ 90%). CONCLUSIONS: Patients with CMS show marked systemic vascular dysfunction. Structural and functional alterations contribute to this problem that may predispose these patients to premature cardiovascular disease. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.
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Doença da Altitude/fisiopatologia , Artérias Carótidas/fisiopatologia , Rigidez Vascular/fisiologia , Vasodilatação/fisiologia , Altitude , Doença da Altitude/sangue , Doença da Altitude/terapia , Velocidade do Fluxo Sanguíneo , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Doença Crônica , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Oxigenoterapia/métodos , Prognóstico , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Ultrassonografia DopplerRESUMO
BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem in mountainous regions of the world. In its more advanced stages, exercise intolerance is often found, but the underlying mechanism is not known. Recent evidence indicates that exercise-induced pulmonary hypertension is markedly exaggerated in CMS. We speculated that this problem may cause pulmonary fluid accumulation and aggravate hypoxemia during exercise. METHODS: We assessed extravascular lung water (chest ultrasonography), pulmonary artery pressure, and left ventricular function in 15 patients with CMS and 20 control subjects at rest and during exercise at 3,600 m. RESULTS: Exercise at high altitude rapidly induced pulmonary interstitial fluid accumulation in all patients but one (14 of 15) with CMS and further aggravated the preexisting hypoxemia. In contrast, in healthy high-altitude dwellers exercise did not induce fluid accumulation in the majority of subjects (16 of 20) (P = .002 vs CMS) and did not alter arterial oxygenation. Exercise-induced pulmonary interstitial fluid accumulation and hypoxemia in patients with CMS was accompanied by a more than two times larger increase of pulmonary artery pressure than in control subjects (P < .001), but no evidence of left ventricular dysfunction. Oxygen inhalation markedly attenuated the exercise-induced pulmonary hypertension (P < .01) and interstitial fluid accumulation (P < .05) in patients with CMS but had no detectable effects in control subjects. CONCLUSIONS: To our knowledge, these findings provide the first direct evidence that exercise induces rapid interstitial lung fluid accumulation and hypoxemia in patients with CMS that appear to be related to exaggerated pulmonary hypertension. We suggest that this problem contributes to exercise intolerance in patients with CMS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.
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Doença da Altitude/fisiopatologia , Exercício Físico/fisiologia , Água Extravascular Pulmonar/metabolismo , Doença da Altitude/terapia , Doença Crônica , Ecocardiografia , Teste de Esforço , Hemodinâmica , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , UltrassonografiaAssuntos
Doenças Transmissíveis Emergentes/complicações , Doenças Transmissíveis Emergentes/virologia , Metapneumovirus/isolamento & purificação , Metapneumovirus/patogenicidade , Infecções por Paramyxoviridae/complicações , Infecções por Paramyxoviridae/virologia , Síndrome do Desconforto Respiratório/virologia , Hospitalização/estatística & dados numéricos , Humanos , Lactente , MasculinoRESUMO
Until today the role of oxygen in the development of the fetus remains controversially discussed. It is still believed that lack of oxygen in utero might be responsible for some of the known congenital cardiovascular malformations. Over the last two decades detailed research has given us new insights and a better understanding of embryogenesis and fetal growth. But most importantly it has repeatedly demonstrated that oxygen only plays a minor role in the early intrauterine development. After organogenesis has taken place hypoxia becomes more important during the second and third trimester of pregnancy when fetal growth occurs. This review will briefly adress causes and mechanisms leading to intrauterine hypoxia and their impact on the fetal cardiovascular system.
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BACKGROUND: Adverse events in utero may predispose to cardiovascular disease in adulthood. The underlying mechanisms are unknown. During preeclampsia, vasculotoxic factors are released into the maternal circulation by the diseased placenta. We speculated that these factors pass the placental barrier and leave a defect in the circulation of the offspring that predisposes to a pathological response later in life. The hypoxia associated with high-altitude exposure is expected to facilitate the detection of this problem. METHODS AND RESULTS: We assessed pulmonary artery pressure (by Doppler echocardiography) and flow-mediated dilation of the brachial artery in 48 offspring of women with preeclampsia and 90 offspring of women with normal pregnancies born and permanently living at the same high-altitude location (3600 m). Pulmonary artery pressure was roughly 30% higher (mean+/-SD, 32.1+/-5.6 versus 25.3+/-4.7 mm Hg; P<0.001) and flow-mediated dilation was 30% smaller (6.3+/-1.2% versus 8.3+/-1.4%; P<0.0001) in offspring of mothers with preeclampsia than in control subjects. A strong inverse relationship existed between flow-mediated dilation and pulmonary artery pressure (r=-0.61, P<0.001). The vascular dysfunction was related to preeclampsia itself because siblings of offspring of mothers with preeclampsia who were born after a normal pregnancy had normal vascular function. Augmented oxidative stress may represent an underlying mechanism because thiobarbituric acid-reactive substances plasma concentration was increased in offspring of mothers with preeclampsia. CONCLUSIONS: Preeclampsia leaves a persistent defect in the systemic and the pulmonary circulation of the offspring. This defect predisposes to exaggerated hypoxic pulmonary hypertension already during childhood and may contribute to premature cardiovascular disease in the systemic circulation later in life.
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Hipertensão Pulmonar/etiologia , Hipóxia/etiologia , Doenças Vasculares Periféricas/etiologia , Pré-Eclâmpsia/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adolescente , Fatores Etários , Monóxido de Carbono/metabolismo , Criança , Ecocardiografia Doppler , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Masculino , Estresse Oxidativo/fisiologia , Doenças Vasculares Periféricas/fisiopatologia , Gravidez , Pressão Propulsora Pulmonar/fisiologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vasodilatação/fisiologia , Pressão Ventricular/fisiologia , Adulto JovemRESUMO
Invasive studies suggest that healthy children living at high altitude display pulmonary hypertension, but the data to support this assumption are sparse. Nitric oxide (NO) synthesized by the respiratory epithelium regulates pulmonary artery pressure, and its synthesis was reported to be increased in Aymara high-altitude dwellers. We hypothesized that pulmonary artery pressure will be lower in Aymara children than in children of European ancestry at high altitude, and that this will be related to increased respiratory NO. We therefore compared pulmonary artery pressure and exhaled NO (a marker of respiratory epithelial NO synthesis) between large groups of healthy children of Aymara (n = 200; mean +/- SD age, 9.5 +/- 3.6 years) and European ancestry (n = 77) living at high altitude (3,600 to 4,000 m). We also studied a group of European children (n = 29) living at low altitude. The systolic right ventricular to right atrial pressure gradient in the Aymara children was normal, even though significantly higher than the gradient measured in European children at low altitude (22.5 +/- 6.1 mm Hg vs 17.7 +/- 3.1 mm Hg, p < 0.001). In children of European ancestry studied at high altitude, the pressure gradient was 33% higher than in the Aymara children (30.0 +/- 5.3 mm Hg vs 22.5 +/- 6.1 mm Hg, p < 0.0001). In contrast to what was expected, exhaled NO tended to be lower in Aymara children than in European children living at the same altitude (12.4 +/- 8.8 parts per billion [ppb] vs 16.1 +/- 11.1 ppb, p = 0.06) and was not related to pulmonary artery pressure in either group. Aymara children are protected from hypoxic pulmonary hypertension at high altitude. This protection does not appear to be related to increased respiratory NO synthesis.
Assuntos
Altitude , Expiração/fisiologia , Hipertensão Pulmonar/etnologia , Óxido Nítrico/metabolismo , Pressão Propulsora Pulmonar/fisiologia , Adaptação Fisiológica , Adolescente , Ar/análise , Bolívia/epidemiologia , Criança , Pré-Escolar , Europa (Continente)/etnologia , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Incidência , Lactente , Masculino , Fatores de RiscoRESUMO
BACKGROUND: In humans, it is not known whether physical endurance exercise training promotes coronary collateral growth. The following hypotheses were tested: the expected collateral flow reduction after percutaneous coronary intervention of a stenotic lesion is prevented by endurance exercise training; collateral flow supplied to an angiographically normal coronary artery improves in response to exercise training; there is a direct relationship between the change of fitness after training and the coronary collateral flow change. METHODS AND RESULTS: Forty patients (age 61+/-8 years) underwent a 3-month endurance exercise training program with baseline and follow-up assessments of coronary collateral flow. Patients were divided into an exercise training group (n=24) and a sedentary group (n=16) according to the fact whether they adhered or not to the prescribed exercise program, and whether or not they showed increased endurance (VO2max in ml/min per kg) and performance (W/kg) during follow-up versus baseline bicycle spiroergometry. Collateral flow index (no unit) was obtained using pressure sensor guidewires positioned in the coronary artery undergoing percutaneous coronary intervention and in a normal vessel. In the vessel initially undergoing percutaneous coronary intervention, there was an increase in collateral flow index among exercising but not sedentary patients from 0.155+/-0.081 to 0.204+/-0.056 (P=0.03) and from 0.189+/-0.084 to 0.212+/-0.077 (NS), respectively. In the normal vessel, collateral flow index changes were from 0.176+/-0.075 to 0.227+/-0.070 in the exercise group (P=0.0002), and from 0.219+/-0.103 to 0.238+/-0.086 in the sedentary group (NS). A direct correlation existed between the change in collateral flow index from baseline to follow-up and the respective alteration of VO2max (P=0.007) and Watt (P=0.03). CONCLUSION: A 3-month endurance exercise training program augments coronary collateral supply to normal vessels, and even to previously stenotic arteries having undergone percutaneous coronary intervention before initiating the program. There appears to be a dose-response relation between coronary collateral flow augmentation and exercise capacity gained.
Assuntos
Circulação Colateral , Circulação Coronária , Estenose Coronária/fisiopatologia , Estenose Coronária/terapia , Terapia por Exercício , Resistência Física , Idoso , Angioplastia Coronária com Balão , Velocidade do Fluxo Sanguíneo , Cateterismo Cardíaco , Estudos de Casos e Controles , Colesterol/sangue , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Eletrocardiografia , Teste de Esforço , Feminino , Seguimentos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Desempenho Psicomotor , Projetos de Pesquisa , Índice de Gravidade de Doença , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
CONTEXT: Individuals susceptible to high-altitude pulmonary edema (HAPE) are characterized by exaggerated pulmonary hypertension and arterial hypoxemia at high altitude, but the underlying mechanism is incompletely understood. Anecdotal evidence suggests that shunting across a patent foramen ovale (PFO) may exacerbate hypoxemia in HAPE. OBJECTIVE: We hypothesized that PFO is more frequent in HAPE-susceptible individuals and may contribute to more severe arterial hypoxemia at high altitude. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of 16 HAPE-susceptible participants and 19 mountaineers resistant to this condition (repeated climbing to peaks above 4000 m and no symptoms of HAPE). MAIN OUTCOME MEASURES: Presence of PFO determined by transesophageal echocardiography, estimated pulmonary artery pressure by Doppler echocardiography, and arterial oxygen saturation measured by pulse oximetry in HAPE-susceptible and HAPE-resistant participants at low (550 m) and high altitude (4559 m). RESULTS: The frequency of PFO was more than 4 times higher in HAPE-susceptible than in HAPE-resistant participants, both at low altitude (56% vs 11%, P = .004; odds ratio [OR], 10.9 [95% confidence interval {CI}, 1.9-64.0]) and high altitude (69% vs 16%, P = .001; OR, 11.7 [95% CI, 2.3-59.5]). At high altitude, mean (SD) arterial oxygen saturation prior to the onset of pulmonary edema was significantly lower in HAPE-susceptible participants than in the control group (73% [10%] vs 83% [7%], P = .001). Moreover, in the HAPE-susceptible group, participants with a large PFO had more severe arterial hypoxemia (65% [6%] vs 77% [8%], P = .02) than those with smaller or no PFO. CONCLUSIONS: Patent foramen ovale was roughly 4 times more frequent in HAPE-susceptible mountaineers than in participants resistant to this condition. At high altitude, HAPE-susceptible participants with a large PFO had more severe hypoxemia. We speculate that at high altitude, a large PFO may contribute to exaggerated arterial hypoxemia and facilitate HAPE.
Assuntos
Doença da Altitude/fisiopatologia , Altitude , Comunicação Interatrial/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Edema Pulmonar/etiologia , Adulto , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Circulação Coronária , Ecocardiografia Doppler , Ecocardiografia Transesofagiana , Feminino , Comunicação Interatrial/complicações , Comunicação Interatrial/diagnóstico por imagem , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Montanhismo , Oximetria , Artéria PulmonarRESUMO
Studies of high-altitude populations, and in particular of maladapted subgroups, may provide important insight into underlying mechanisms involved in the pathogenesis of hypoxemia-related disease states in general. Over the past decade, studies involving short-term hypoxic exposure have greatly advanced our knowledge regarding underlying mechanisms and predisposing events of hypoxic pulmonary hypertension. Studies in high altitude pulmonary edema (HAPE)-prone subjects, a condition characterized by exaggerated hypoxic pulmonary hypertension, have provided evidence for the central role of pulmonary vascular endothelial and respiratory epithelial nitric oxide (NO) for pulmonary artery pressure homeostasis. More recently, it has been shown that pathological events during the perinatal period (possibly by impairing pulmonary NO synthesis), predispose to exaggerated hypoxic pulmonary hypertension later in life. In an attempt to translate some of this new knowledge to the understanding of underlying mechanisms and predisposing events of chronic hypoxic pulmonary hypertension, we have recently initiated a series of studies among high-risk subpopulations (experiments of nature) of high-altitude dwellers. These studies have allowed to identify novel risk factors and underlying mechanisms that may predispose to sustained hypoxic pulmonary hypertension. The aim of this article is to briefly review this new data, and demonstrate that insufficient NO synthesis/bioavailability, possibly related in part to augmented oxidative stress, may represent an important underlying mechanism predisposing to pulmonary hypertension in high-altitude dwellers.