Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study.

BACKGROUND: Epidemiological studies suggest that obesity-induced atherosclerosis may start in childhood, but this process has never been demonstrated. We looked for arterial changes and investigated their relation to cardiovascular risk factors in obese children. METHODS: Non-invasive ultrasonographic measurements were made in 48 severely obese children and 27 controls to investigate arterial mechanics and endothelial function. Plasma lipid concentrations, indices of insulin resistance, and body composition were assessed in the obese children. FINDINGS: The obese children had significantly lower arterial compliance than the healthy controls (median 0.132 [0.022-0.273] vs 0.143 [0.112-0.237] mm(2).mm Hg; p=0.02) and lower distensibility (0.60 [0.10-1.00] vs 0.70 [0.50-1.10] mm Hg(-1).10(-2); p=0.0001). Conversely, the obese children had higher values than the controls for wall stress (3.36 [2.00-5.01] vs 2.65 [2.13-3.54] mm Hg.10(2); p=0.0001) and incremental elastic modulus (1.68 [0.72-10.8] vs 0.96 [0.64-1.47]; p=0.0001). Endothelium-dependent and independent function were also lower in the obese than in the control children. An android fat distribution was positively correlated with indices of insulin resistance and plasma triglyceride concentrations and was negatively correlated with plasma HDL-cholesterol concentration and arterial compliance. Endothelial dysfunction was correlated with low plasma apolipoprotein A-I and with insulin resistance indices. INTERPRETATION: Severe obesity in children is associated with arterial wall stiffness and endothelial dysfunction. Low plasma apolipoprotein A-I, insulin resistance, and android fat distribution may be the main risk factors for these arterial changes, which are of considerable concern as possible early events in the genesis of atheroma.

Resting energy expenditure before and after surgical resection of gut lesions in pediatric Crohn's disease.

In pediatric Crohn's disease (CD), resection of gut lesions is necessary to remove stenoses and when frequent relapses occur despite nutritional support and medical treatment. After surgery, improved nutritional status and accelerated growth usually follow increased nutritional intake and lower doses of steroids. The aim of this study was to compare energy balance before and after surgery while nutritional intake and steroid therapy were unchanged. Eleven patients, aged 14.5 +/- 2.5 years and with mildly active CD, were explored 1 week before and 1 month after gut resection for stenosis (n = 7) and medical treatment failure (n = 4). Eleven matched children participated in the study as controls. Disease activity was assessed by the Pediatric Crohn's Disease Activity Index and serum orosomucoid concentration. Resting energy expenditure (REE) was measured by indirect calorimetry, and fat-free body mass (FFM) was measured by anthropometry. The patients' mean REE decreased from 46.6 +/- 10.5 kcal/kg FFM/day before surgery to 42.6 +/- 10.3 kcal/kg FFM/day after surgery, while the controls' mean REE was 39 +/- 7 kcal/kg FFM/day (analysis of variance, p = 0.02). After surgery, body weights were not significantly different, but the mean protein oxidation rate was reduced and arm muscle area was increased. Changes in REE per kilogram of FFM per day were not correlated with changes in orosomucoid serum concentrations (r2 = 0.35; p = 0.4). In conclusion, in children with mildly active CD, while nutritional intake and steroid therapy were maintained at preoperative levels, a significant decrease in REE and improved nitrogen utilisation were observed 1 month after resection of the CD gut lesion. This finding suggests better use of energy substrates when CD lesions are removed.

Atrial natriuretic factor during fetal and postnatal life: a review.

This review summarizes current understanding of the role of atrial natriuretic factor (ANF) during fetal and postnatal life. The cardiac localization of ANF synthesis changes during development from ventricular to predominantly atrial cardiocytes. ANF is present as a circulating hormone during fetal life and fetal plasma ANF clearance rates and production rates are higher than in adults. ANF is a natriuretic hormone in fetal and newborn animals. However, unlike the adult, this natriuresis does not appear to be related to suppression of the renin-angiotensin system. During fetal life, ANF levels can be increased through both atrial distension and humoral influences. Hence, mechanisms of ANF release during development appear to be similar to those present at maturity.

Renal hemodynamic response to atrial natriuretic factor in fetal and newborn sheep.

We have previously demonstrated that systemic atrial natriuretic factor (ANF) infusion induced a renal vasoconstrictor response in fetal and newborn sheep. The present study was designed to test the hypothesis that the fetal and neonatal renal vasculatures do, in fact, vasodilate in response to ANF but that this effect is negated by vasoconstrictor compensatory mechanisms when ANF is infused systemically. To test this hypothesis, the renal hemodynamic response to intrarenal infusion of ANF was studied in chronically instrumented fetal (125-135 d of gestation; term 145 d) and newborn (8-15 d) sheep. Intrarenal infusion of ANF (0.125 to 4.0 micrograms/kg of body wt in fetuses and 0.25 to 8.0 micrograms/kg in newborns) had no significant effect on mean arterial blood pressure and heart rate. However, ANF produced a concentration-dependent increase in renal blood flow velocity (F = 40.9, p less than 0.001) and a decrease in renal vascular resistance (F = 38.3, p less than 0.001) in both groups. The magnitude of changes in renal blood flow velocity and renal vascular resistance expressed as percentage of changes (% delta) from control values, were similar (p greater than 0.05) in both fetal and newborn sheep during intrarenal infusion of ANF. These results demonstrate that ANF exerts direct vasodilator action on the fetal and neonatal renal vasculature and that the renal vasoconstriction previously observed during systemic infusion of ANF was probably secondary to activation of compensatory mechanisms.

Plasma and urinary clearance rates of atrial natriuretic factor during ontogeny in sheep.

The present study was designed to determine the plasma clearance rate of atrial natriuretic factor (ANF) during development in chronically-instrumented fetal, newborn and adult non-pregnant sheep. To determine the contribution of the kidney in the metabolism of ANF, urinary clearance of ANF was also measured. Intravenous infusion of ANF (0.025 and 0.1 microgram.min-1.kg-1) produced a significant decrease in mean arterial blood pressure in newborn lambs and in adult non-pregnant sheep. Estimated plasma ANF clearance rate for the 0.025 and 0.1 microgram.min-1.kg-1 ANF infusion rate were respectively 177 +/- 55 and 155 +/- 34 ml.min-1.kg-1 in fetuses, 138 +/- 26 and 97 +/- 13 ml.min-1.kg-1 in newborn lambs and, 148 +/- 33 and 103 +/- 25 ml.min-1.kg-1 in adult nonpregnant ewes. Fetal, newborn and adult ANF plasma clearance rates during high ANF infusion rate (0.1 microgram.min-1.kg-1) were not significantly different. Low or high ANF infusion rate was not associated with significant changes in urinary ANF concentration or urinary ANF excretion rate. Taken together, the present study demonstrates that ANF plasma clearance rate is similar in fetal, newborn and adult non-pregnant sheep and that the excretory function of the kidney contributes only minimally to ANF plasma clearance rate.

Ontogeny of the renal response to natriuretic peptide in sheep.

The ontogeny of the renal response to continuous systemic infusion of atrial natriuretic peptide (ANP) was studied in chronically instrumented fetal, newborn, and adult nonpregnant sheep. Plasma immunoreactive ANP (ANPir) concentrations during low (0.025 microgram.kg-1.min-1) and high rate (0.1 microgram.kg-1.min-1) ANP infusion were similar between each group of animals. Decrease in renal blood flow velocity (RBFV) and rise in renal vascular resistance (RVR) were observed in fetal and newborn lambs during ANP infusion. The percent changes in RBFV and RVR were of significantly (P less than 0.05) greater magnitude during high ANP infusion rate in fetuses (-28.5 +/- 8.5 and 93 +/- 6.4%) than in adult sheep (-6.6 +/- 3.2 and -4.4 +/- 4.9%). ANP produced no changes in urine flow (V) in fetuses but increased V significantly in newborn lambs and adult sheep. Glomerular filtration rate increased significantly during ANP infusion in adult sheep but not in fetal and newborn lambs. Percentage changes in urinary excretion rate of Na (UNaV) during high ANP infusion rate were significantly higher in adult sheep (3,520 +/- 2,414%) than in newborn (157 +/- 106%) and fetal lambs (198 +/- 84%). These results suggest that the cardiovascular, renal hemodynamic, and possibly renal function responses to continuous ANP infusion increase during maturation, the overall response being larger in adult animals.