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PubMed1997

The solution structure of the N-terminal domain of alpha2-macroglobulin receptor-associated protein.

The three-dimensional structure of the N-terminal domain (residues 18-112) of alpha2-macroglobulin receptor-associated protein (RAP) has been determined by NMR spectroscopy. The structure consists of three helices composed of residues 23-34, 39-65, and 73-88. The three helices are arranged in an up-down-up antiparallel topology. The C-terminal 20 residues were shown not to be in a well defined conformation. A structural model for the binding of RAP to the family of low-density lipoprotein receptors is proposed. It defines a role in binding for both the unordered C terminus and the structural scaffold of the core structure. Pathogenic epitopes for the rat disease Heymann nephritis, an experimental model of human membranous glomerulonephritis, have been identified in RAP and in the large endocytic receptor gp330/megalin. Here we provide the three-dimensional structure of the pathogenic epitope in RAP. The amino acid residues known to form the epitope are in a helix-loop-helix conformation, and from the structure it is possible to rationalize the published results obtained from studies of fragments of the N-terminal domain.

Animals↗

PubMed1997

Identification of the second cluster of ligand-binding repeats in megalin as a site for receptor-ligand interactions.

Megalin is a large cell surface receptor that mediates the binding and internalization of a number of structurally and functionally distinct ligands from the lipoprotein and protease:protease inhibitor families. To begin to address how megalin is able to bind ligands with unique structurally properties, we have mapped a binding site for apolipoprotein E (apoE)-beta very low density lipoprotein (beta VLDL), lipoprotein lipase, aprotinin, lactoferrin, and the receptor-associated protein (RAP) within the primary sequence of the receptor. RAP is known to inhibit the binding of all ligands to megalin. We identified a ligand-binding site on megalin by raising mAb against purified megalin, selected for a mAb whose binding to megalin is inhibited by RAP, and mapped the epitope for this mAb. mAb AC10 inhibited the binding of apoE-beta VLDL, lipoprotein lipase, aprotinin, and lactoferrin to megalin in a concentration-dependent manner. When cDNA fragments encoding the four cysteine-rich ligand-binding repeats in megalin were expressed in a baculovirus system and immunoblotted with AC10, it recognized only the second cluster of ligand-binding repeats. The location of the epitope recognized by mAb AC10 within this domain was pinpointed to amino acids 1111-1210. From these studies we conclude that the binding of apoE-beta VLDL, lactoferrin, aprotinin, lipoprotein lipase, and RAP to megalin is either competitively or sterically inhibited by mAb AC10 suggesting that these ligands bind to the same or closely overlapping sites within the second cluster of ligand-binding repeats.

Animals↗

PubMed1999

Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase.

Lipoprotein lipase and the receptor-associated protein (RAP) bind to overlapping sites on the low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor (LRP). We have investigated if lipoprotein lipase interacts with the RAP binding but structurally distinct receptor sortilin/neurotensin receptor-3. We show, by chemical cross-linking and surface plasmon resonance analysis, that soluble sortilin binds lipoprotein lipase with an affinity similar to that of LRP. The binding was inhibited by heparin and RAP and by the newly discovered sortilin ligand neurotensin. In 35S-labeled 3T3-L1 adipocytes treated with the cross-linker dithiobis(succinimidyl propionate), lipoprotein lipase-containing complexes were isolated by anti-sortilin antibodies. To elucidate function in cells, sortilin-negative Chinese hamster ovary cells were transfected with full-length sortilin and shown to express about 8% of the receptors on the cell surface. These cells degraded 125I-labeled lipoprotein lipase much faster than the wild-type cells. The degradation was inhibited by unlabeled lipoprotein lipase, indicating a saturable pathway, and by RAP and heparin. Moreover, inhibition by the weak base chloroquine suggested that degradation occurs in an acidic vesicle compartment. The results demonstrate that sortilin is a multifunctional receptor that binds lipoprotein lipase and, when expressed on the cell surface, mediates its endocytosis and degradation.

Adaptor Proteins, Vesicular Transport↗

PubMed1999

Role of the low density lipoprotein-related protein receptor in mediation of factor VIII catabolism.

In the present study, we found that catabolism of coagulation factor VIII (fVIII) is mediated by the low density lipoprotein receptor-related protein (LPR), a liver multiligand endocytic receptor. In a solid phase assay, fVIII was shown to bind to LRP (K(d) 116 nM). The specificity was confirmed by a complete inhibition of fVIII/LRP binding by 39-kDa receptor-associated protein (RAP), an antagonist of all LRP ligands. The region of fVIII involved in its binding to LRP was localized within the A2 domain residues 484-509, based on the ability of the isolated A2 domain and the synthetic A2 domain peptide 484-509 to prevent fVIII interaction with LRP. Since vWf did not inhibit fVIII binding to LRP, we proposed that LRP receptor may internalize fVIII from its complex with vWf. Consistent with this hypothesis, mouse embryonic fibroblasts that express LRP, but not fibroblasts genetically deficient in LRP, were able to catabolize (125)I-fVIII complexed with vWf, which was not internalized by the cells. These processes could be inhibited by RAP and A2 subunit of fVIII, indicating that cellular internalization and degradation were mediated by interaction of the A2 domain of fVIII with LRP. In vivo studies of (125)I-fVIII.vWf complex clearance in mice demonstrated that RAP completely inhibited the fast phase of the biphasic (125)I-fVIII clearance that is responsible for removal of 60% of fVIII from circulation. Inhibition of the RAP-sensitive phase prolonged the half-life of (125)I-fVIII in circulation by 3.3-fold, indicating that LRP receptor plays an important role in fVIII clearance.

Amino Acids↗

PubMed2001

The low density lipoprotein receptor-related protein contributes to selective uptake of high density lipoprotein cholesteryl esters by SW872 liposarcoma cells and primary human adipocytes.

The concept that selective transfer of high density lipoprotein (HDL)-derived cholesteryl esters (CE) does not require lipoprotein internalization has been challenged recently by evidence that implicates HDL recycling during the selective uptake process. This has prompted us to examine the role of the low density lipoprotein receptor-related protein (LRP) in selective uptake. LRP is an endocytic receptor for lipoprotein lipase (LpL) and apolipoprotein E (apoE) ligands that are able to mediate selective uptake. We report that molecules that interfere with ligand binding to LRP, such as the receptor-associated protein (RAP), suramin, alpha(2)-macroglobulin, or lactoferrin, inhibit HDL-CE selective uptake by human primary adipocytes and SW872 liposarcoma cells by 35-50%. This partial inhibition of selective uptake from total HDL was not due to preferential inhibition of the HDL(2) or HDL(3) subfractions. Selective uptake by the scavenger receptor BI was not inhibited by RAP, excluding its involvement. Furthermore, in SW872 cells in which LRP was reduced to 14% of control levels by stable antisense expression, selective uptake was attenuated by at least 33%, confirming a role for LRP in this process. RAP, alpha(2)-macroglobulin, lactoferrin, and suramin (individually or in paired combinations) also attenuated selective uptake of HDL-CE by primary human adipocytes by about 40%. On the other hand, human skin fibroblasts express LRP abundantly but lack the capacity for selective uptake, demonstrating that other molecules are required. In SW872 cells, exogenous apoE or LpL can facilitate selective uptake but only the apoE-enhanced uptake can be inhibited by RAP, implicating apoE as a likely co-mediator. We discuss the possible mechanisms by which the endocytic receptor, LRP, can mediate selective uptake.

Adipocytes↗

PubMed2002

CCAAT/enhancer-binding proteins beta and delta mediate the repression of gene transcription of cartilage-derived retinoic acid-sensitive protein induced by interleukin-1 beta.

Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a secreted protein expressed by chondrocytes; the expression is repressed by interleukin 1 beta (IL-1 beta). To investigate the transcriptional mechanism, by which CD-RAP expression is suppressed by IL-1 beta, deletion constructs of the mouse CD-RAP promoter were transfected into rat chondrocytes treated with or without IL-1 beta. The results revealed an IL-1 beta-responsive element located between -2138 and -2068 bp. As this element contains a CAAT/enhancer-binding protein (C/EBP) motif, the function of C/EBP beta and C/EBP delta was examined. IL-1 beta stimulated the expression of C/EBP beta and -delta, and the direct binding of C/EBP beta to the C/EBP motif was confirmed. The -2251-bp CD-RAP promoter activity was down-regulated by co-transfection with C/EBP expression vectors. Mutation of the C/EBP motif abolished the inhibitory response to IL-1 beta. Additionally, C/EBP expression vectors were found to down-regulate the construct containing the promoter and enhancer of the type II collagen gene. Finally, the enhancer factor, Sox9, was shown to bind adjacent to the C/EBP site competing with C/EBP binding. Taken together, these results suggest that C/EBP beta and -delta may play an important role in the IL-1 beta-induced repression of cartilage-specific proteins and that expression of matrix proteins will be influenced by the availability of positive and negative trans-acting factors.

Animals↗

PubMed2004

Low density lipoprotein receptor-related protein mediates endocytic clearance of pro-MMP-2.TIMP-2 complex through a thrombospondin-independent mechanism.

The low density lipoprotein receptor-related protein (LRP) mediates the endocytic clearance of various proteinases and proteinase.inhibitor complexes, including thrombospondin (TSP)-dependent endocytosis of matrix metalloproteinase (MMP)-2 (or gelatinase A), a key effector of extracellular matrix remodeling and cancer progression. However, the zymogen of MMP-2 (pro-MMP-2) mostly occurs in tissues as a complex with the tissue inhibitor of MMPs (TIMP-2). Here we show that clearance of the pro-MMP-2.TIMP-2 complex is also mediated by LRP, because addition of receptor-associated protein (RAP), a natural LRP ligand antagonist, inhibited endocytosis and lysosomal degradation of (125)I-pro-MMP-2.TIMP-2. Both TIMP-2 and the pro-MMP-2 collagen-binding domain independently competed for endocytosis of (125)I-pro-MMP-2.TIMP-2 complex. Surface plasmon resonance studies indicated that pro-MMP-2, TIMP-2, and pro-MMP-2.TIMP-2 directly interact with LRP in the absence of TSP. LRP-mediated endocytic clearance of (125)I-pro-MMP-2 was inhibited by anti-TSP antibodies and accelerated upon complexing with TSP-1, but these treatments had no effect on (125)I-pro-MMP-2.TIMP-2 uptake. This implies that mechanisms of clearance by LRP of pro-MMP-2 and pro-MMP-2.TIMP-2 complex are different. Interestingly, RAP did not inhibit binding of (125)I-pro-MMP-2.TIMP-2 to the cell surface. We conclude that clearance of pro-MMP-2.TIMP-2 complex is a TSP-independent two-step process, involving (i) initial binding to the cell membrane in a RAP-insensitive manner and (ii) subsequent LRP-dependent (RAP-sensitive) internalization and degradation.

Binding Sites↗

PubMed2005

AF6 negatively regulates Rap1-induced cell adhesion.

AF6 is involved in the connection of membrane-associated proteins to the actin cytoskeleton. It binds to Ras-like small GTPases and is suggested to be an effector of both Ras and Rap. Here we show that knockdown of AF6 in T cells by RNA interference enhanced Rap1-induced integrin-mediated cell adhesion, whereas overexpression of AF6 had the opposite effect. Interestingly, AF6-induced inhibition of cell adhesion correlated with an increase in RapGTP levels. Like AF6, protein KIAA1849 contains a Ras association domain and interacted with Rap1. However, KIAA1849 did not inhibit Rap1-induced cell adhesion. We concluded that AF6 is a negative regulator of Rap-induced cell adhesion. We proposed that AF6 inhibits Rap-mediated cell adhesion by sequestering RapGTP in an unproductive complex and thus prevents the interaction of Rap1 not only with effectors that mediate adhesion but also with Rap GTPase-activating proteins. Thus, AF6 may buffer RapGTP in resting T cells and maintain them in a non-adherent state.

Blotting, Western↗

PubMed2006

The single ligand-binding repeat of Tva, a low density lipoprotein receptor-related protein, contains two ligand-binding surfaces.

The receptor for avian sarcoma/leukosis virus subtype A (ASLV-A), Tva, is the simplest member of the low density lipoprotein receptor family containing a single ligand-binding repeat (LBR). Most LBRs contain a central Trp (Trp33 in Tva) that is important for ligand binding and, for the low density lipoprotein receptor, is associated with familial hypercholesterolemia. The Tva ligand-binding module contains a second Trp (Trp48) that is part of a DEW motif present in a subset of LBRs. Trp48 is important for ASLV-A infectivity. A soluble Tva (sTva) ligand-binding module is sufficient for ASLV-A infectivity. Tva interacts with the viral glycoprotein, and a soluble receptor-binding domain (SUA) binds sTva with picomolar affinity. We investigated whether Tva, a retroviral receptor, could behave as a classic LBR by assessing sTva interactions with the universal receptor-associated protein (RAP) and comparing these interactions with those between sTva and its viral ligand (SUA). To address the role of the two Trp residues in Tva function, we prepared sTva harboring mutations of Trp33, Trp48, or both and determined the binding kinetics with RAP and SUA. We found that sTva behaved as a "normal" receptor toward RAP, requiring both calcium and Trp33 for binding. However, sTva binding to SUA required neither calcium nor Trp33. Furthermore, sTva could bind both RAP and SUA simultaneously. These results show that the single LBR of Tva has two ligand-binding sites, raising the possibility that other LBRs may also.

Amino Acid Sequence↗

PubMed2003

Intragastric maldistribution of a liquid meal in children with recurrent abdominal pain assessed by three-dimensional ultrasonography.

BACKGROUND: Using two-dimensional (2D) ultrasonography, we previously found indications of impaired adaptive relaxation of the proximal stomach in children with recurrent abdominal pain (RAP). In the present study, we applied a new three-dimensional (3D) ultrasonographic method to investigate intragastric volumes and distribution of a liquid meal in another group of children with RAP. METHODS: Twenty patients with RAP (age 10-15 years) and 20 healthy subjects (age 11-15 years) underwent ultrasonographic measurements of the stomach. A position sensor was used based on magnetic scanhead tracking for acquisition of 3D images after a liquid meal. The children scored abdominal symptoms before and after the meal. RESULTS: Expressed as a fraction of ingested volume, the patients had a smaller volume of the proximal stomach and a larger antral volume at 2 min postprandially compared to healthy subjects (P = 0.03 and P = 0.001, respectively). The patients also showed a decreased proximal to distal gastric volume ratio at 2 min postprandially (P = 0.001). Patients experienced more pain in response to the meal than healthy subjects (P = 0.04), but there was no correlation between pain and proximal or distal gastric volumes. CONCLUSIONS: RAP in children may be associated with an early intragastric maldistribution of a meal.

Abdominal Pain↗

PubMed2004

Recurrent abdominal pain in children revisited: irritable bowel syndrome and psychosomatic aspects. A prospective study.

BACKGROUND: Since Apley, more than 40 years ago, concluded that less than 10% of cases with recurrent abdominal pain (RAP) are of organic origin, medical technology has improved, the knowledge has expanded and new methods of investigation have been developed. The lack of organic findings in many children with RAP has led to the conclusion that psychological factors are important. METHODS: Forty-four children with RAP underwent an investigation programme to find organic abnormalities that might explain the symptoms. Current criteria for irritable bowel syndrome (IBS) in children were used to find out what proportion fulfilled these criteria, irrespective of the organic findings on clinical investigation. A standardized questionnaire, the CBCL (Child Behaviour Checklist), was used to evaluate emotional and behavioural disturbances in children referred for RAP. RESULTS: Thirteen out of 26 (50%) children with no signs of organic disease fulfilled the IBS criteria as opposed to 7 out of 18 (39%) children in the group with organic findings (P = 0.68). The total score for the CBCL was in the normal range for 32 out of 36 of the children. CONCLUSIONS: We found a high proportion of children fulfilling the IBS criteria in both groups, thus organic abnormalities have to be excluded before making the IBS diagnosis. The results of the CBCL forms did not show any difference between children with organic versus those with non-organic abnormalities, both groups within the normal range.

Abdominal Pain↗

PubMed2000

Influence of feeding regimens on non-invasive inferior vena cava and hepatic vein velocity measurements in infants.

UNLABELLED: The aim of this study was to investigate the effects of feeding type and osmotic load on intravascular volume status. Ninety term, healthy infants 2 mo of age were included in the study. The breastfed and formula-fed groups each consisted of 45 infants. Echocardiographic examination was performed before and after feeding. The collapse index of the inferior vena cava (IVCIC) and right atrial pressure (RAP) were calculated. No statistically significant differences were found between before- and after-feeding values of IVCIC, RAP and hepatic vein velocities in breastfed infants. In the formula-fed group, after-feeding values of IVCIC were significantly lower and RAP, hepatic vein systolic and diastolic velocities were significantly higher compared to the before-feeding values. Most of the mothers (78%) were unsuccessful at preparing the formula at appropriate concentrations. No statistically significant differences were found between the before-and after-feeding values of IVCIC, RAP and hepatic vein velocities in infants being fed appropriately prepared formula. The after-feeding values of hepatic vein velocities were higher than those of before-feeding values; after-feeding values of IVCIC were lower than before-feeding values in infants being fed highly concentrated formula. CONCLUSION: The values of inferior vena cava indices and hepatic vein velocities were not effected by feeding in infants receiving appropriately concentrated formula, like those of infants receiving breast milk. However, feeding with highly concentrated formula may cause intravascular volume expansion.

Blood Flow Velocity↗

PubMed2006

Central/diffuse abdominal perception of urological pain in children.

AIM: In children with recurrent abdominal pain (RAP), the location of pain to the flank may suggest the involvement of the urinary apparatus. We aimed to evaluate the location of pain in different age groups of children with idiopathic hypercalciuria (HC) and/or hyperuricosuria (HU) and RAP. METHODS: Location of pain was assessed in 180 consecutive HC/HU children with RAP, aged 3-17.6 y, presenting to a single centre. RESULTS: Considering four age groups, central/diffuse was more prevalent than lateral location of pain in youngsters, with a progressive and significant (p<0.0001, chi2 test for trend) decrease of the prevalence of central/diffuse location with rising age, and with the most relevant drop after age 8 y. Location of pain was central/diffuse in 81% of patients under and lateral in 79% of those over 8 y of age (p<0.0001). The location of pain changed from central/diffuse to lateral in 16/18 children followed at least 1 y, within 1 to 2 y by age 8. CONCLUSION: Only after 8 y of age did the lateral location of abdominal pain become the rule in children with HC/HU and RAP. This has to be kept in mind in order to avoid overlooking the urologic origin of pain.

Abdominal Pain↗

PubMed1999

Upper gastrointestinal disease, Helicobacter pylori and recurrent abdominal pain.

Over a 5-y period, 396 children complaining of recurrent abdominal pain (RAP) underwent upper gastrointestinal endoscopy in order to identify any underlying organic pathology and determine the prevalence of Helicobacter pylori (H. pylori) infection. Histologically confirmed mucosal inflammation was found in 338 out of 396 children (85.4%); in 113 of 396 patients (28.5%), H. pylori was identified on the gastric mucosa. Significant discriminating factors between H. pylori positive and negative children with RAP included age (mean age for positive 11 y vs. 8.1 y for negative, p < 0.01) and gender (male gender predominance in the H. pylori positive, p < 0.001). No significant difference was found between H. pylori positive and negative groups regarding incidence and character of the presenting symptoms. All H. pylori positive children (100%) had abnormal histology compared with 225 out of 283 negative ones (79.5%). Histologically confirmed gastritis was the most prominent finding in H. pylori positive children compared with H. pylori negative (98.2% vs. 19%, p < 0.001). Conversely, oesophagitis was more common in H. pylori negative children (47.7% vs. 27.4%, p < 0.001). The incidence of peptic ulcer was higher in H. pylori infected patients than in the H. pylori negative group (5.3% vs. 1%, p < 0.05). Our data suggest that gastrointestinal pathology is more common than previously thought in children with RAP, while H. pylori infection is a relatively important factor in the etiology of upper gastrointestinal inflammation in RAP syndrome.

Abdominal Pain↗

PubMed2003

Quality of life after hip fracture: a comparison of four health status measures in 208 patients.

OBJECTIVES: We compared four health status measures for the evaluation of quality of life after hip fracture. METHODS: Two hundred and eight elderly hip fracture patients were followed up to 4 months after hospital admission. We used two interviewer-administered instruments (the Rehabilitation Activities Profile (RAP) and the Barthel Index (BI)) that focus on functional status, and two self-assessment instruments (the Nottingham Health Profile (NHP) and the COOP/WONCA charts) that additionally include psychological and social health domains. The score distribution, internal consistency, construct validity, and sensitivity to change were investigated. RESULTS: At 4 months only 18% of surviving patients had reached the same level of functioning as before the fracture and, compared with reference values, lower scores of health status were found in the areas of physical mobility and emotional reactions. The number of comorbidities at hospital admission was the most important prognostic factor for recovery of health status at 4 months. The RAP and the BI both performed well in the assessment of functional status in regard to score distribution, internal consistency and construct validity. In contrast to the BI, the RAP also assessed instrumental activities of daily living and perceived problems with existing disabilities. The generic health status measures produced no added value in the assessment of functional status. The NHP covered a wider range of psychological health dimensions (emotion, pain, energy, and sleep) and had better psychometric properties than COOP/WONCA. None of the four instruments performed well in assessing social functioning. CONCLUSIONS: To assess health status after hip fracture, we recommend the RAP for functional status and the NHP for changes in emotion, pain, and energy. These instruments detected poor recovery in functional and emotional status at 4 months after fracture.

Activities of Daily Living↗

PubMed1996

Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (LRP) and heparan sulfate proteoglycans.

Speed and selectivity of hepatocyte invasion by malaria sporozoites have suggested a receptor-mediated mechanism and the specific interaction of the circumsporozoite (CS) protein with liver-specific heparan sulfate proteoglycans (HSPGs) has been implicated in the targeting to the liver. Here we show that the CS protein interacts not only with cell surface heparan sulfate, but also with the low density lipoprotein receptor-related protein (LRP). Binding of 125I-CS protein to purified LRP occurs with a Kd of 4.9 nM and can be inhibited by the receptor-associated protein (RAP). Blockage of LRP by RAP or anti-LRP antibodies on heparan sulfate-deficient CHO cells results in more than 90% inhibition of binding and endocytosis of recombinant CS protein. Conversely, blockage or enzymatic removal of the cell surface heparan sulfate from LRP-deficient embryonic mouse fibroblasts yields the same degree of inhibition. Heparinase-pretreatment of LRP-deficient fibroblasts or blockage of LRP on heparan sulfate-deficient CHO cells by RAP, lactoferrin, or anti-LRP antibodies reduces Plasmodium berghei invasion by 60-70%. Parasite development in heparinase-pretreated HepG2 cells is inhibited by 65% when RAP is present during sporozoite invasion. These findings suggest that malaria sporozoites utilize the interaction of the CS protein with HSPGs and LRP as the major mechanism for host cell invasion.

Animals↗

PubMed1997

Immunization with Babesia bigemina rhoptry-associated protein 1 induces a type 1 cytokine response.

Rhoptry-associated protein-1 (RAP-1) homologues of Babesia bigemina and Babesia bovis are promising candidates for inclusion in subunit vaccines against these hemoprotozoan parasites. Partial protection against challenge infection has been achieved with native forms of these antigens, but the mechanism of immunity has not been thoroughly defined. We previously demonstrated that a panel of antigen-specific T helper cell clones derived from B. bigemina RAP-1-immunized cattle expressed relatively high levels of interferon-gamma (IFN-gamma) protein and transcript and low levels of interleukin-4 (IL-4), indicative of a type 1 immune response. In the current study we present evidence that subcutaneous immunization with native B. bigemina RAP-1 protein in RIBI adjuvant induces a predominant type 1 immune response in vivo, characterized by relatively high levels of IFN-gamma and IL-2 and low levels of IL-4 and IL-10 mRNA in the draining prescapular lymph node. Ex vivo restimulation of draining lymph node lymphocytes with specific antigen resulted in proliferation and enhanced expression of IL-2 and IFN-gamma, whereas IL-4 and IL-10 transcript levels remained relatively low. These findings show that our previously described cytokine profiles of antigen-specific cloned T cell lines are representative of autologous in vivo responses and confirm that type 1 recall responses to B. bigemina RAP-1 can be evoked in immunized animals by native parasite antigen.

Animals↗

PubMed1994

Prevention of venous air embolism in paediatric neurosurgical procedures performed in the sitting position by combined use of MAST suit and PEEP.

We studied 60 children undergoing neurosurgical procedures in the sitting position. Routine monitoring included ECG, pulse oximetry, invasive arterial pressure, in particular mean arterial pressure (MAP), and right atrial pressure (RAP). Children were allocated to two groups. In group B lower body positive pressure and positive end-expiratory pressure (PEEP) were used for preventing venous air embolism (VAE). In this group, antishock trousers (MAST suit) were adjusted in supine children. After induction of anaesthesia, different positions were studied: supine and sitting before MAST suit inflation, sitting with MAST suit inflated up to a pressure of 40 mmHg in the lower compartments and 30 mmHg in the abdominal compartment, and finally a combination of lower body positive pressure and PEEP of 8-10 cm H2O. In group A no MAST suit or PEEP was used. Continuous monitoring of end-tidal carbon dioxide pressure throughout (PE'CO2) was used to detect VAE. In order to evaluate the transmission of pressures from the right atrium to the veins at the base of the skull, jugular bulb venous pressure (JBVP) was measured in 20 patients by retrograde catheterization. The incidence of VAE was compared in the two groups. On placing children into the sitting position, a significant decrease in RAP and JBVP was noted without significant changes in MAP in the two groups. Inflation of the MAST suit induced a dramatic increase in RAP and JBVP, reinforced by addition of PEEP. There was a strong positive relationship between RAP and JBVP. There were no deleterious side effects or differences between the two groups in peroperative blood product requirements or surgical general conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗