Surgical programme at Royal Alexandra Hospital, Sydney, for Papua New Guinea children with congenital heart disease, 1978-1994

Objective : To report the history of the Royal Alexandra Hospital for Children (RAHC) Papua New Guinea (PNG) cardiac surgical programme and describe the selection, preoperative clinical features and postoperative outcome of children with congenital heart disease managed by the programme. Methods : Details for each of the PNG cardiac patients admitted to RAHC following selection by visiting cardiologists between 1978 and 1994 were entered into a database, and analysed and interpreted. Results : A congenital heart defect was confirmed in 165 of the 170 children selected. The male to female ratio was 1:1 and the mean age on admission to RAHC was 5.5 years. Almost all of the children for whom data were available (98%) had a weight for age and 41% had a height for age less than the 3rd centile. One-sixth had delayed milestones. A large number were tachypnoeic, in heart failure, or had pulmonary hypertension on admission. Ventricular septal defect and tetralogy of Fallot were the commonest defects, and lesions such as aortic stenosis, coarctation of the aorta and transposition of the great arteries were absent or rare. Thirty-one (19%) of the children selected initially did not receive surgery because of pulmonary hypertension, or because the lesions did not fall within the programme guidelines for operation. One hundred and twenty-nine children had corrective and four had palliative procedures. Half of the operated children had postoperative complications. Eight children died, all following open-heart procedures, giving a case fatality rate of 6%. Preoperative tachypnoea, hepatomegaly, cardiac failure and pulmonary hypertension were strongly associated with poor outcome. Conclusions : The programme was an arduous exercise for all organizations concerned, but achieved comparatively good short-term outcomes. The experience gained should assist in planning for similar programmes.

Will chymase inhibitors be the next major development for the treatment of cardiovascular disorders?

Chymase is contained in the secretory granules of mast cells. In addition to the synthesis of angiotensin II, chymase is involved in transforming growth factor-beta activation and cleaves Type I procollagen to produce collagen. NK301 and BCEAB are orally-active inhibitors of chymase. NK301 was tested in a dog model of vascular intimal hyperplasia after balloon injury and shown to reduce the increased chymase activity in the injured arteries and prevent intimal thickening. In a hamster model of cardiac fibrosis associated with cardiomyopathy, BCEAB reduced the increased cardiac chymase activity in cardiomyopathy and reduced fibrosis. Chymase inhibitors may be an important development for the treatment of cardiovascular injury associated with mast cell degranulation.

Potentiation of 5-hydroxytryptamine (5-HT) responses by a 5-HT uptake inhibitor in pulmonary and systemic vessels: effects of exposing rats to hypoxia

The aim was to determine whether uptake of 5-hydroxytryptamine (5-HT) by the 5-HT transporter (SERT) modulates contractile responses to 5-HT in rat pulmonary arteries and whether this modulation is altered by exposure of rats to chronic hypoxia (10% oxygen; 8 h/day; 5 days). The effects of the SERT inhibitor, citalopram (100 nM), on contractions to 5-HT were determined in isolated ring preparations of pulmonary artery (intralobar and main) and compared with data obtained in systemic arteries. In intralobar pulmonary arteries citalopram produced a potentiation (viz. an increase in potency, pEC(50)) of 5-HT. The potentiation was endothelium-dependent in preparations from normoxic rats but endothelium-independent in preparations from hypoxic rats. In main pulmonary artery endothelium-independent potentiation was seen in preparations from hypoxic rats but no potentiation occurred in preparations from normoxic rats. In systemic arteries, citalopram caused endothelium-independent potentiation in aorta but no potentiation in mesenteric arteries; there were no differences between hypoxic and normoxic rats. It is concluded that SERT can influence the concentration of 5-HT in the vicinity of the vasoconstrictor receptors in pulmonary arteries. The data suggest that in pulmonary arteries from hypoxic rats, unlike normoxic rats, the SERT responsible for this effect is not in the endothelium and, hence, is probably in the smooth muscle. The data are compatible with reports that, in the pulmonary circulation, hypoxia induces/up-regulates SERT, and hence increases 5-HT uptake, in vascular smooth muscle. The findings may have implications in relation to the suggested use of SERT inhibitors in the treatment of pulmonary hypertension.

Alterations in pulmonary vascular function in rats exposed to intermittent hypoxia

Vasoactive agents were examined in arteries from control rats and rats exposed to intermittent hypoxia (10% oxygen; 8 h/day) for 3, 5 or 20 days. Hypoxic rats developed right ventricular hypertrophy after 5 days, but became pulmonary hypertensive (elevated right ventricular systolic pressure; RVSP) only after 20 days. In pulmonary arteries (main and intralobar), responses to acetylcholine and ionomycin (endothelium-dependent vasodilators) were reduced after 20 and 5 days of intermittent hypoxia, whereas contractions to 5-hydroxytryptamine (5-HT) were enhanced (potency increase >10-fold) after 20, 5 and 3 days. Contractions to endothelin-1 and a thromboxane-mimetic, but not Ca-2divided by, were also increased. No changes in vascular function occurred in aorta. Since changes in pulmonary vascular function preceded the increase in RVSP they do not result from, but may contribute to, the development of hypoxia-induced pulmonary hypertension. If similar changes occur in humans, they may be important in conditions characterised by intermittent, as opposed to continuous, hypoxia. (C) 2003 Elsevier B.V. All rights reserved.

S-nitrosocaptopril: acute in-vivo pulmonary vasodepressor effects in pulmonary hypertensive rats

The effects of S-nitrosocaptopril (SNOcap), administered either intravenously or by oral gavage, on pulmonary artery pressure (PAP) were examined in anaesthetised normotensive rats and rats with hypoxic pulmonary hypertension (10% oxygen for 1 week). Mean PAP (MPAP) values in hypoxic and normoxic rats were (mmHg) 26 +/- 1.7 and 15 +/- 1.1, respectively. When given intravenously, 1 mg kg(-1) SNOcap reduced MPAP by 28 and 32% in hypoxic and normoxic rats, respectively. The effects of 2 mg kg(-1) were no greater than those of 1 mg kg(-1). Pulmonary vasoclepressor responses reached equilibrium in 1.7 +/- 0.18 min following intravenous administration. When given orally 30 min before the measurement of PAP, 30 mg kg(-1), but not 10 mg kg(-1), significantly reduced MPAP in hypoxic rats to 17 +/- 1.5 mmHg. These in-vivo data are consistent with previous in-vitro data showing that SNOcap has direct pulmonary vasorelaxant properties in both large and small pulmonary arteries and also show that SNOcap causes pulmonary vasodepression in the setting of pulmonary hypertension. Since SNOcap also inhibits pulmonary vascular angiotensin converting enzyme (ACE) in pulmonary blood vessels (previous study), it would be an interesting drug with which to assess the benefits of direct pulmonary vasodilatation combined with ACE inhibition (which attentuates pulmonary vascular remodelling) in a long-term study in pulmonary hypertension.

Acute lead-induced vasoconstriction in the vascular beds of isolated perfused rat tails is endothelium-dependent

Chronic lead exposure induces hypertension in humans and animals, affecting endothelial function. However, studies concerning acute cardiovascular effects are lacking. We investigated the effects of acute administration of a high concentration of lead acetate (100 µΜ) on the pressor response to phenylephrine (PHE) in the tail vascular bed of male Wistar rats. Animals were anesthetized with sodium pentobarbital and heparinized. The tail artery was dissected and cannulated for drug infusion and mean perfusion pressure measurements. Endothelium and vascular smooth muscle relaxation were tested with acetylcholine (5 µg/100 µL) and sodium nitroprusside (0.1 µg/100 µL), respectively, in arteries precontracted with 0.1 µM PHE. Concentration-response curves to PHE (0.001-300 µg/100 µL) were constructed before and after perfusion for 1 h with 100 µΜ lead acetate. In the presence of endothelium (E+), lead acetate increased maximal response (Emax) (control: 364.4 ± 36, Pb2+: 480.0 ± 27 mmHg; P < 0.05) and the sensitivity (pD2; control: 1.98 ± 0.07, 2.38 ± 0.14 log mM) to PHE. In the absence of endothelium (E-) lead had no effect but increased baseline perfusion pressure (E+: 79.5 ± 2.4, E-: 118 ± 2.2 mmHg; P < 0.05). To investigate the underlying mechanisms, this protocol was repeated after treatment with 100 µM L-NAME, 10 µM indomethacin and 1 µM tempol in the presence of lead. Lead actions on Emax and pD2 were abolished in the presence of indomethacin, and partially abolished with L-NAME and tempol. Results suggest that acute lead administration affects the endothelium, releasing cyclooxygenase-derived vasoconstrictors and involving reactive oxygen species.

Reactivity of the isolated perfused rat tail vascular bed

Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg) and heparinized (500 U). The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 µM EDTA at 36oC and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE) (0.5, 1, 2 and 5 µg, bolus injection) was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min). The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5, 2, 2.5, 3 and 3.5 ml/min) at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM) in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 µg/ml). There was an enhancement of the effect of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity.

Cell-specific regulation of acetylcholinesterase expression under inflammatory conditions

Acetylcholine (ACh) has been shown to exert an anti-inflammatory function by down-modulating the expression of pro-inflammatory cytokines. Its availability can be regulated at different levels, namely at its synthesis and degradation steps. Accordingly, the expression of acetylcholinesterase (AChE), the enzyme responsible for ACh hydrolysis, has been observed to be modulated in inflammation. To further address the mechanisms underlying this effect, we aimed here at characterizing AChE expression in distinct cellular types pivotal to the inflammatory response. This study was performed in the human acute leukaemia monocytyc cell line, THP-1, in human monocyte-derived primary macrophages and in human umbilical cord vein endothelial cells (HUVEC). In order to subject these cells to inflammatory conditions, THP-1 and macrophage were treated with lipopolysaccharide (LPS) from E.coli and HUVEC were stimulated with the tumour necrosis factor α (TNF-α). Our results showed that although AChE expression was generally up-regulated at the mRNA level under inflammatory conditions, distinct AChE protein expression profiles were aurprisingly observed among the distinct cellular types studied. Altogether, these results argue for the existence of cell specific mechanisms that regulate the expression of acetylcholinesterase in inflammation.

Endocardite infecciosa e acidente vascular cerebral: mecanismos fisiopatológicos e avaliação ultrassonográfica

Uma das mais graves complicações da endocardite infecciosa é o acidente vascular cerebral isquémico, responsável por uma alta taxa de mortalidade e morbilidade nos países desenvolvidos. Embora não seja o mecanismo dominante, o cardioembolismo é responsável por cerca de 20% dos enfartes cerebrais isquémicos. Sabe-se que o embolismo cerebral afeta mais de 40% dos pacientes com endocardite infecciosa, uma vez que a embolização da vegetação resultante da infeção das estruturas intracardíacas para a circulação arterial pode levar à oclusão das artérias cerebrais, dando origem, assim, a enfarte por ausência de aporte sanguíneo. O desenvolvimento de técnicas não invasivas baseadas na ultrassonografia tem potenciado um amplo estudo destas patologias, quer a nível cardíaco, quer vascular, promovendo uma melhor compreensão dos mecanismos fisiopatológicos que as envolvem. A ecocardiografia e o Doppler transcraniano detêm um papel central, respetivamente, no diagnóstico e predição do risco de fenómenos embólicos em pacientes com endocardite infecciosa e na avaliação inicial, prognóstico e follow-up de um episódio de acidente vascular cerebral.

Relationship between the iron status of pregnant women and their newborns

OBJECTIVE: To determine the relationship between iron nutritional status of pregnant women and their newborns using a combination of hematological and biochemical parameters for the diagnosis of iron deficiency. METHODS: A cross-sectional study was conducted in Jundiaí, Southeastern Brazil, in 2000. Venous blood samples collected from 95 pregnant women and from their umbilical cord and used for the determination of complete blood count, serum iron, total iron-binding capacity, serum ferritin, zinc protoporphyrin, and transferrin saturation. Women were classified into three groups: anemic, iron deficient and non-iron deficient. Statistical analysis included the Tukey-HSD test, Pearson's correlation coefficient and multiple linear regression analysis. RESULTS: Among pregnant women, 19% were anemic (97.9% mildly anemic and 2.1% moderately anemic) and 30.5% were iron deficient. No significant difference was seen in mean values of any parameter studied between newborns in the three groups (p>0.05). Multiple linear regression analysis showed weak association between neonatal and maternal parameters. CONCLUSIONS: The iron nutritional status of pregnant women with iron deficiency or mild anemia does not seem to have a significant impact on the iron levels of their children.

Epidemiologia das hemoglobinopatias: variabilidade genética da hemoglobina e de enzimas eritrocitárias no Hospital Provincial do Bengo, Caxito, Angola

As hemoglobinopatias são doenças hereditárias resultado de alterações na síntese de cadeias de globina e incluem alterações estruturais e talassemias que são provocadas pela produção diminuída de globina. Se não for diagnosticada e tratada, muitas das hemoglobinopatias resultam em morte nos primeiros anos de vida. Dada a importância do tema e a escassez de dados no nosso meio iniciou-se o estudo das mesmas no Hospital Provincial do Bengo (HGB).

Optimising protocol of acquisition and post-processing procedures in the assessment of coronary artery disease by computed tomography

Coronary artery disease (CAD) is currently one of the most prevalent diseases in the world population and calcium deposits in coronary arteries are one direct risk factor. These can be assessed by the calcium score (CS) application, available via a computed tomography (CT) scan, which gives an accurate indication of the development of the disease. However, the ionising radiation applied to patients is high. This study aimed to optimise the protocol acquisition in order to reduce the radiation dose and explain the flow of procedures to quantify CAD. The main differences in the clinical results, when automated or semiautomated post-processing is used, will be shown, and the epidemiology, imaging, risk factors and prognosis of the disease described. The software steps and the values that allow the risk of developingCADto be predicted will be presented. A64-row multidetector CT scan with dual source and two phantoms (pig hearts) were used to demonstrate the advantages and disadvantages of the Agatston method. The tube energy was balanced. Two measurements were obtained in each of the three experimental protocols (64, 128, 256 mAs). Considerable changes appeared between the values of CS relating to the protocol variation. The predefined standard protocol provided the lowest dose of radiation (0.43 mGy). This study found that the variation in the radiation dose between protocols, taking into consideration the dose control systems attached to the CT equipment and image quality, was not sufficient to justify changing the default protocol provided by the manufacturer.

Tempo de clampeamento e fatores associados à reserva de ferro de neonatos a termo

OBJETIVO : Analisar o impacto do tempo de clampeamento e parâmetros obstétricos, biológicos e socioeconômicos sobre a reserva de ferro de neonatos nascidos a termo. MÉTODOS : Estudo transversal pelo qual foram avaliados os parâmetros hematológicos de neonatos de Viçosa, MG, de outubro de 2011 a julho de 2012. Foram coletados 7 mL de sangue do cordão umbilical de 144 neonatos a termo e sem baixo peso. Os parâmetros investigados foram: hemograma completo, ferro sérico, ferritina e proteína C-reativa. O tempo de clampeamento do cordão umbilical foi mensurado utilizando cronômetro digital sem interferir nos procedimentos do parto. Os dados de nascimento foram coletados nas Declarações de Nascidos Vivos e as demais informações foram obtidas com a mãe do neonato por aplicação de questionário no primeiro mês pós-parto. Realizou-se análise de regressão linear múltipla visando a estimar a influência de variáveis obstétricas, biológicas e socioeconômicas nos níveis de ferritina ao nascer. RESULTADOS : A mediana de ferritina foi 130,3 µg/L (n = 129, mínimo de 16,4 e máximo 420,5 µg/L), a média de ferro sérico foi 137,9 μg/dL (n = 144, dp = 39,29) e de hemoglobina, 14,7 g/dL (n = 144, dp = 1,47). O tempo mediano de clampeamento do cordão foi 36 segundos, variando entre sete e 100. A análise bivariada detectou associação entre os níveis de ferritina e a cor da criança, tempo de clampeamento de 60 segundos, tipo de parto, a presença de diabetes gestacional e a renda per capita da família. Renda per capita, número de consultas pré-natais e o comprimento ao nascer contribuíram com 22,0% da variação dos níveis de ferritina na análise múltipla. CONCLUSÕES : A reserva de ferro ao nascer sofreu influência de características biológicas, obstétricas e sociais. O combate à anemia deve envolver a implementação de um critério de clampeamento tardio do cordão umbilical para as diretrizes de trabalho de parto, bem como a criação de políticas voltadas para a redução das desigualdades sociais e melhoria da qualidade do atendimento pré-natal.

Factors associated with arterial stiffness in children aged 9-10 years

OBJECTIVE To analyze the factors associated with stiffness of the great arteries in prepubertal children.METHODS This study with convenience sample of 231 schoolchildren aged 9-10 years enrolled in public and private schools in Vitória, ES, Southeastern Brazil, in 2010-2011. Anthropometric and hemodynamic data, blood pressure, and pulse wave velocity in the carotid-femoral segment were obtained. Data on current and previous health conditions were obtained by questionnaire and notes on the child’s health card. Multiple linear regression was applied to identify the partial and total contribution of the factors in determining the pulse wave velocity values.RESULTS Among the students, 50.2% were female and 55.4% were 10 years old. Among those classified in the last tertile of pulse wave velocity, 60.0% were overweight, with higher mean blood pressure, waist circumference, and waist-to-height ratio. Birth weight was not associated with pulse wave velocity. After multiple linear regression analysis, body mass index (BMI) and diastolic blood pressure remained in the model.CONCLUSIONS BMI was the most important factor in determining arterial stiffness in children aged 9-10 years.