Hypothesis acardiac twin pregnancies: Pathophysiology-based hypotheses suggest risk prediction by pump/acardiac umbilical venous diameter ratios.

BACKGROUND: A total of 75% of monozygotic twins share 1 monochorionic placenta where placental anastomoses cause several serious complications, for example, acardiac twinning. Acardiac twins lack cardiac function but grow by perfusion of arterial blood from the pump twin. This rare pregnancy has 50% natural pump twin mortality but accurate risk prediction is currently impossible. Recent guidelines suggest prophylactic surgery before 18 weeks, suggesting 50% unnecessary interventions. We hypothesize that (1) adverse pump twin outcome relates to easy-to-measure pump/acardiac umbilical venous diameter (UVD) ratios, representing acardiac perfusion by the pump's excess cardiac output. This hypothesis suggests that (2) UVD-ratios are large, mildly varying in cases without complications but small and decreasing when complications develop, thus predicting that (3) UVD-ratios may allow risk prediction of pump twins. In this exploratory clinical pilot, we tested whether UVD-ratio measurements support these predictions. METHODS: We included 7 uncomplicated (expectant management), 3 elective surgical, and 17 complicated cases (pump decompensation, emergency intervention/delivery or demise). Nine UVD-ratios were measured sonographycally and 18 by pathology. RESULTS: Uncomplicated cases have larger, two serial measurements showing mildly varying UVD-ratios; elective surgical cases show larger UVD-ratios; complicated cases have smaller, two serial measurements showing decreasing UVD-ratios. There were no false-positives, no false-negatives and noncrossing linear trendlines of uncomplicated and complicated cohorts. CONCLUSION: Our data provide first evidence that UVD-ratios allow risk prediction of pump twins. More early uncomplicated and late complicated cases are needed, for example, in a prospective trial, before the separation between uncomplicated and complicated cohorts is accurate enough to support a well-founded decision on (early) intervention.

Congenital umbilical arterio-venous malformation: a word of caution.

We report on an 18-month old girl who presented in good clinical shape with a pulsatile tumour in the umbilical area which had a shape and localization similar to that of an umbilical bowel hernia. The Doppler ultrasound of the umbilical tumour revealed a large arterio-venous vascular malformation with a haemodynamically significant blood shunting. Furthermore, the inferior caval vein and the hepatic veins were dilated. Computed tomography angiography revealed permeable umbilical veins and arteries communicating within a large dilated arterio-venous fistula. The growing tumour was excised without any perioperative complications. Further postoperative recovery was uneventful and the baby was discharged 10 days after surgery. We advocate careful antenatal ultrasound evaluation of these vascular malformations. Early surgical removal in newborns is vital in order to avoid severe complications.

C2238 atrial natriuretic peptide molecular variant is associated with endothelial damage and dysfunction through natriuretic peptide receptor C signaling.

RATIONALE: C2238 atrial natriuretic peptide (ANP) minor allele (substitution of thymidine with cytosine in position 2238) associates with increased risk of cardiovascular events. OBJECTIVE: We investigated the mechanisms underlying the vascular effects of C2238-αANP. METHODS AND RESULTS: In vitro, human umbilical vein endothelial cell were exposed to either wild-type (T2238)- or mutant (C2238)-αANP. Cell survival and apoptosis were tested by Trypan blue, annexin V, and cleaved caspase-3 assays. C2238-αANP significantly reduced human umbilical vein endothelial cell survival and increased apoptosis. In addition, C2238-αANP reduced endothelial tube formation, as assessed by matrigel. C2238-αANP did not differentially modulate natriuretic peptide receptor (NPR)-A/B activity with respect to T2238-αANP, as evaluated by intracellular cGMP levels. In contrast, C2238-αANP, but not T2238-αANP, markedly reduced intracellular cAMP levels in an NPR-C-dependent manner. Accordingly, C2238-αANP showed higher affinity binding to NPR-C, than T2238-αANP. Either NPR-C inhibition by antisense oligonucleotide or NPR-C gene silencing by small interfering RNA rescued survival and tube formation of human umbilical vein endothelial cell exposed to C2238-αANP. Similar data were obtained in human aortic endothelial cell with NPR-C knockdown. NPR-C activation by C2238-αANP inhibited the protein kinase A/Akt1 pathway and increased reactive oxygen species. Adenovirus-mediated Akt1 reactivation rescued the detrimental effects of C2238-αANP. Overall, these data indicate that C2238-αANP affects endothelial cell integrity through NPR-C-dependent inhibition of the cAMP/protein kinase A/Akt1 pathway and increased reactive oxygen species production. Accordingly, C2238-αANP caused impairment of acetylcholine-dependent vasorelaxation ex vivo, which was rescued by NPR-C pharmacological inhibition. Finally, subjects carrying C2238 minor allele showed early endothelial dysfunction, which highlights the clinical relevance of our results. CONCLUSIONS: C2238-αANP reduces endothelial cell survival and impairs endothelial function through NPR-C signaling. NPR-C targeting represents a potential strategy to reduce cardiovascular risk in C2238 minor-allele carriers.

Ginkgo biloba extract attenuates oxLDL-induced endothelial dysfunction via an AMPK-dependent mechanism.

Atherosclerosis is a complex inflammatory arterial disease, and oxidized low-density lipoprotein (oxLDL) is directly associated with chronic vascular inflammation. Previous studies have shown that Ginkgo biloba extract (GbE) acts as a therapeutic agent for neurological and cardiovascular disorders. However, the mechanisms mediating the actions of GbE are still largely unknown. In the present study, we tested the hypothesis that GbE protects against oxLDL-induced endothelial dysfunction via an AMP-activated protein kinase (AMPK)-dependent mechanism. Human umbilical vein endothelial cells were treated with GbE, followed by oxLDL, for indicated time periods. Results from Western blot showed that GbE inhibited the membrane translocation of the NADPH oxidase subunits p47(phox) and Rac-1 and attenuated the increase in protein expression of membrane subunits gp91 and p22(phox) caused by oxLDL-induced AMPK dephosphorylation and subsequent PKC activation. AMPK-α(1)-specific small interfering RNA-transfected cells that had been exposed to GbE followed by oxLDL revealed elevated levels of PKC and p47(phox). In addition, exposure to oxLDL resulted in reduced AMPK-mediated Akt/endothelial nitric oxide (NO) synthase signaling and the induction of phosphorylation of p38 mitogen-activated protein kinase, which, in turn, activated NF-κB-mediated inflammatory responses, such as the release of interleukin-8, the expression of the adhesion molecule, and the adherence of monocytic cells to human umbilical vein endothelial cells. Furthermore, oxLDL upregulated the expression of inducible NO synthase, thereby augmenting the formation of NO and protein nitrosylation. Pretreatment with GbE, however, exerted significant cytoprotective effects in a dose-dependent manner. Results from this study may provide insight into a possible molecular mechanism by which GbE protects against oxLDL-induced endothelial dysfunction.

Extracorporeal portal vein arterialization in man after extended hepatectomy to prevent acute liver failure: a case report.

Experimental studies have shown that increasing the oxygen supply to the liver through portal vein arterialization (PVA) enhances liver regeneration after partial hepatectomy. Moreover, our previous study demonstrated a beneficial effect of an extracorporeal device to increase the oxygenated blood to the liver and to improve the survival rate of animals subjected to subtotal hepatectomy. Herein we have reported a case of PVA through an extracorporeal device to treat a man after extended hepatectomy leading to acute liver failure (ALF). An obese 69-year-old man (body mass index > 35) affected by multiple metastases from colorectal cancer underwent 80% liver resection; at laparotomy, a steatotic liver was evident due to adjuvant chemotherapy. Moreover, the liver experienced 20 minutes of hepatic ischemia during the resection. At the end of resection he underwent extracorporeal PVA treatment. Blood was withdrawn from the femoral artery and returned into the portal venous system through the umbilical vein. An extracorporeal device was interposed between the outflow and inflow to monitor hemodynamic parameters. Starting from operating room each of six treatments lasted 6 hours per day. Serum and liver samples were collected daily. The extracorporeal device was dismounted at the seventh postoperative day. The postoperative course was assessed at 1 month. The PVA-extracorporeal treatment yielded beneficial effects for subtotal hepatectomy by decreasing serum ammonia, transaminases, and total bilirubin concentration. The international normalized ratio recovered rapidly, remaining significantly lower during the entire postoperative period. The ten-day postoperative period was uneventful. The patient was discharged in good health. He is alive and well at the moment. The arterial blood supply in the portal system through the umbilical vein using an extracorporeal device was easily applicable, efficacious, safe, and cost-effective. It may represent a novel approach to treat patients with potential ALF after subtotal liver resection.

Human serum albumin improves endothelial dysfunction and survival during experimental endotoxemia: concentration-dependent properties.

OBJECTIVES: The mechanisms by which human serum albumin might protect against sepsis-induced organ dysfunction and improve survival are not elucidated. The present study was designed to assess the effects of two concentrations of human serum albumin on endotoxin-induced mortality as well as on endothelial and organ dysfunctions in both mouse and cell models. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University research laboratories. SUBJECTS: Swiss mice (n = 10-15/group) were injected with either lipopolysaccharide or vehicle. Four and 12 hrs later, mice were infused or not with human serum albumin HSA (4% or 20%, 10 mL/kg) or normal saline (0.9% NaCl, 30 mL/kg). Human uterine vein endothelial cells were exposed to both lipopolysaccharide and tumor necrosis factor-α during 8 hrs in the presence or absence of human serum albumin (4% or 20%). MEASUREMENTS AND MAIN RESULTS: Mice survival, reactivity of mesenteric arteries, and Western blot protein analysis were assessed. Circulating endothelin-1, gluthatione, gluthatione disulfide, and creatinine plasma levels were measured. Nitric oxide production, oxidative, and nitrosative stresses were also measured in situ in endothelial cells. Human serum albumin 4%, but not human serum albumin 20% or normal saline solution, improved survival time of endotoxemic mice. Furthermore, human serum albumin 4% activated endothelial nitric oxide synthase and restored lipopolysaccharide-impaired flow-dependent endothelial dilation in mesenteric arteries. This was associated with a downregulation of nuclear factor κB and an upregulation of nuclear respiratory factor-2 and heme oxygenase-1. Human serum albumin 4% reduced lipopolysaccharide-induced renal dysfunction, enhanced endothelin-1 production and glutathione plasmatic levels, whereas human serum albumin 20% increased gluthatione disulfide. Furthermore, human serum albumin 4% but not 20% blunted lipopolysaccharide-tumor necrosis factor-α-induced oxidative and nitrosative stresses in endothelial cells and increased their gluthatione levels. CONCLUSIONS: The present data confirm a protective effect of 4% human serum albumin treatment both on mice survival and endothelial dysfunction by inhibiting inflammatory and oxidative stress pathways induced by endotoxins. Conversely, higher concentrations of human serum albumin were detrimental suggesting a dose-dependent effect.

Enhanced angiogenic capacity of human umbilical vein endothelial cells from women with preeclampsia.

Maternal and placental angiogenic abnormalities are a common feature of preeclampsia. The aim of this study was to determine if endothelial cells from women with preeclampsia exhibit different angiogenic responses compared to healthy cells. Using the endothelial tube formation assay, we have shown that primary human umbilical vein endothelial cells (HUVECs) isolated from women with preeclampsia display greater levels of in vitro angiogenic branching compared to cells from healthy women. A comparable increase in tube formation was observed in healthy cells cultured at 0.5% O(2). Vascular endothelial growth factor (VEGF) receptor inhibition resulted in a decrease in angiogenesis in both healthy hypoxic cells and cells from women with preeclampsia. These findings demonstrate that HUVECs from women with preeclampsia exhibit inherent differences in their angiogenic capacity which are apparent in the absence of placental or maternal factors.

Assessment of the ductus venosus, tricuspid blood flow and the nasal bone in second-trimester screening for trisomy 21.

OBJECTIVE: To examine the prevalence of reversed a-wave in the ductus venosus, tricuspid regurgitation and absent nasal bone, in a second-trimester population undergoing amniocentesis, after exclusion of major fetal defects and to estimate the performance in screening for trisomy 21 based on maternal age and these markers in a general population. METHODS: This was a retrospective study involving pregnancies undergoing amniocentesis due to increased risk for trisomy 21, mainly because of advanced maternal age. Before the invasive procedure, an ultrasound examination was carried out to exclude major fetal defects and to examine the ductus venosus, tricuspid blood flow and the presence of the fetal nasal bone. Modeling techniques were used based on 20 000 euploid pregnancies and 20 000 pregnancies with trisomy 21 to assess the screening performance in a general population. RESULTS: The study population consisted of 3613 euploid pregnancies and 35 cases with trisomy 21. In the euploid group, reversed flow in the ductus venosus, tricuspid regurgitation and an absent nasal bone was observed in 1.7%, 1.5% and 0.1% of cases, respectively. In the trisomic group, these markers were found in 14.3%, 11.4% and 14.3% of cases, respectively. For a 5% false-positive rate, the detection rate in screening for trisomy 21, based on maternal age and either ductus venosus, tricuspid blood flow or nasal bone would be 33.8%, 32.4% or 31.4%, respectively. Screening by maternal age alone would detect 29.0% of the fetuses with trisomy 21. Receiver-operating characteristics curve analysis showed a slight but significant improvement in screening performance for trisomy 21 based on the inclusion of these markers. CONCLUSION: Second-trimester ultrasound screening for trisomy 21 based on maternal age with additional assessment of the ductus venosus, tricuspid blood flow and the fetal nasal bone in otherwise normal-appearing fetuses is only marginally better than is screening by maternal age alone.

Differential modulation of angiogenesis by advanced glycation end products.

Divergent angiogenic responses occur in different organs in a diabetic state. Many of the pathological effects were mediated by the advanced glycation end products (AGEs) of non-enzymatically glycated molecules. Investigations were carried out using different angiogenic model systems to examine whether the angiogenic response to AGEs is influenced by the cellular microenvironment. AGE-albumin increased angiogenesis in chick chorioallantoic membrane (CAM). It also increased sprouting in rat aortic rings and the expression of angiogenic markers CD31 and E-selectin and the angiogenic growth factor, vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs) in culture, suggesting a proangiogenic effect. But in a serum-supplemented condition, AGE-albumin inhibited aortic sprouting and expression of angiogenic markers and VEGF production by HUVECs, suggesting an antiangiogenic effect in the presence of serum. Blocking of the AGE effect by the antioxidants, N-acetyl cysteine and ascorbic acid, suggested that the AGE effect involved oxidant stress. Reversal of the AGE effect by LY 294 002, an inhibitor of the Akt pathway and increased phosphorylation of Akt in cells maintained in serum-free medium, suggested the involvement of the Akt pathway in mediating the AGE effect; such an effect was absent in a serum-supplemented condition. These opposing effects of AGE-albumin on angiogenesis in the presence and absence of serum suggested that the AGE accumulated in a hyperglycemic condition can affect angiogenesis depending on the microenvironment of the cells.

Effect of umbilical vein blood flow on perinatal outcome of fetuses with lean and/or hypo-coiled umbilical cord.

OBJECTIVE: To evaluate the effect of umbilical vein (UV) blood flow measured by color-directed pulsed-wave Doppler on perinatal outcome of fetuses with lean and/or hypocoiled umbilical cord after 24 weeks of gestation. METHODS: Two hundred and forty-four women with singleton fetus after 24 weeks of gestation were studied. Umbilical cord area, umbilical vessel cross-sectional area and antenatal umbilical coiling index (UCI) were calculated and compared with Doppler parameters including UV blood flow volume in ml/min/kg, UV peak systolic velocity in cm/s, and umbilical artery pulsatility index. RESULTS: Thirty-eight (15.5%) fetuses had lean umbilical cord (area < 10th percentile). A significant difference between fetuses with and those without lean cord was found in terms of: UCI (0.17 ± 0.06 vs. 0.35 ± 0.08, P < 0.001), cord cross-sectional area (89.6 ± 11.7 vs. 198.7 ± 33.7 mm(2), P < 0.001), Wharton's jelly amount (36.5 ± 11.2 vs. 125.2 ± 34.1 mm(2), P < 0.001), UV blood flow (83.4 ± 15.8 vs. 131.0 ± 19.8 ml/min/kg, P < 0.001), and UV blood flow mean velocity (8.6 ± 3.7 vs. 12.1 ± 2.8 cm/s, P < 0.05). A significant positive correlation was found between antenatal UCI and UV blood flow (r = 0.73, P < 0.001). CONCLUSION: Fetuses with lean and/or hypo-coiled umbilical cord showed a noticeable decrease in UV blood flow of sufficient magnitude that could affect fetal growth, and this could explain the higher prevalence of fetal intrapartum complications in growth-restricted fetuses.

IL-18 accelerates the cell apoptosis by up-regulating cysteinyl leukotriene 2 receptor expression in human umbilical vein endothelial cells at the early stage of administration.

The purpose of the present study is to identify whether interleukin (IL)-18 can modulate cysteinyl leukotriene 2 receptor (CysLT2R) expression in Human Umbilical Vein Endothelial Cells (HUVECs) and how it influences the cell death. According to the results from real-time reverse transcription PCR, confocal laser scanning microscopy, and western blotting, a dose-dependent augmentation of CysLT2R protein expression in HUVECs was triggered by IL-18 for the first 2 h followed by down-regulation within the next 22 h after IL-18 administration. The flow cytometry showed that non-selective CysLT1R and CysLT2R antagonist BAY-u9773 could attenuate the early stage apoptosis mediated by IL-18 whereas CysLT1R antagonist Montelukast couldn't. Also, pretreatment with BAY-u9773 suppressed calcium influx of HUVECs induced by IL-18 whereas Montelukast didn't work. The observation that progression of cell death aggravated by IL-18 could be attenuated by BAY-u9773 may offer a chance to develop a novel way to treat arteriosclerosis.

Histone H2AX is integral to hypoxia-driven neovascularization.

H2A histone family member X (H2AX, encoded by H2AFX) and its C-terminal phosphorylation (gamma-H2AX) participates in the DNA damage response and mediates DNA repair. Hypoxia is a physiological stress that induces a replication-associated DNA damage response. Moreover, hypoxia is the major driving force for neovascularization, as the hypoxia-mediated induction of vascular growth factors triggers endothelial cell proliferation. Here we studied the role of the hypoxia-induced DNA damage response in endothelial cell function and in hypoxia-driven neovascularization in vivo. Hypoxia induced replication-associated generation of gamma-H2AX in endothelial cells in vitro and in mice. Both in cultured cells and in mice, endothelial cell proliferation under hypoxic conditions was reduced by H2AX deficiency. Whereas developmental angiogenesis was not affected in H2afx(-/-) mice, hypoxia-induced neovascularization during pathologic proliferative retinopathy, in response to hind limb ischemia or during tumor angiogenesis was substantially lower in H2afx(-/-) mice. Moreover, endothelial-specific H2afx deletion resulted in reduced hypoxia-driven retina neovascularization and tumor neovascularization. Our findings establish that H2AX, and hence activation of the DNA repair response, is needed for endothelial cells to maintain their proliferation under hypoxic conditions and is crucial for hypoxia-driven neovascularization.

Ductus venosus Doppler in screening for trisomies 21, 18 and 13 and Turner syndrome at 11-13 weeks of gestation.

OBJECTIVES: To investigate the performance of first-trimester screening for aneuploidies by including assessment of ductus venosus flow in the combined test of maternal age, fetal nuchal translucency thickness, fetal heart rate, and serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. METHODS: Screening by the combined test was performed in singleton pregnancies, including 19 614 with euploid fetuses, 122 with trisomy 21, 36 with trisomy 18, 20 with trisomy 13 and eight with Turner syndrome. In all cases the a-wave in the fetal ductus venosus flow was assessed. We examined the performance of two screening strategies: first, assessment of the a-wave in all patients and, second, first-stage screening using the combined test in all patients followed by second-stage assessment of the a-wave only in those with an intermediate risk of one in 51 to one in 1000 after the first stage RESULTS: Reversed a-wave was observed in 3.2% of the euploid fetuses, and in 66.4%, 58.3%, 55.0% and 75.0% of fetuses with trisomies 21, 18 and 13 and Turner syndrome, respectively. Inclusion of ductus venosus flow in all pregnancies would detect 96%, 92%, 100% and 100% of trisomies 21, 18 and 13 and Turner syndrome, respectively, at a false-positive rate of 3%. The same detection rates were achieved with the two-stage strategy at a false-positive rate of 2.6%, in which it was necessary to assess the ductus venosus in only 15% of the total population. CONCLUSIONS: Assessment of ductus venosus flow improves the performance of first-trimester screening for aneuploidies.

Intertwin discordance in umbilical venous volume flow: a reflection of blood volume imbalance in twin-to-twin transfusion syndrome.

OBJECTIVES: To compare umbilical venous volume flow (UVVF) between donor and recipient twins in twin-to-twin transfusion syndrome (TTTS) using an index that is independent of gestational age and to correlate changes in this index with outcome following endoscopic laser surgery. METHODS: UVVF was calculated in 84 cases of TTTS by multiplying the umbilical vein cross-sectional area at its entry into the fetal abdomen by time averaged blood velocity. All cases were classified according to the Quintero staging system. The ratio between UVVF in recipients and donors (R/D-UVVF) in each pair of twins was calculated before and 48 h after laser treatment, and changes in R/D-UVVF were correlated with pregnancy outcome. Intraobserver and interobserver UVVF measurement reliability was assessed in 19 singletons, and 13 donor and recipient twins before laser treatment using the intraclass correlation coefficient (ICC). RESULTS: Twenty-five, 32, 21 and six cases presented as Quintero Stages 1, 2, 3 and 4, respectively, at a median gestational age of 20 (range, 15-26) weeks. Intraobserver and interobserver ICC for UVVF measurement in twins were 0.97 and 0.67, respectively. UVVF was a median of 2.13-fold (range, 0.3-19-fold) higher in recipients than in donors (137 mL/min vs. 64 mL/min, P < 0.001) and increased with gestational age (r = 0.58, P < 0.001 for recipients, r = 0.62, P < 0.001 for donors). From 68 cases in which R/D-UVVF could be measured 48 h following laser surgery, cases with a favorable outcome showed a significant decrease in R/D-UVVF from a median of 1.97 to 1.27 (P < 0.01) and cases with recurrent TTTS (n = 6) did not (decrease in R/D-UVVF from a median of 2.32 to 2.19, P = 0.17). Using a cut-off of < 30% reduction of R/D-UVVF, 66% of the cases with recurrence could be predicted, and the odds ratio for recurrence was 3.13 (95% CI, 0.52-18.29). A significant UVVF imbalance between recipient and donor twins was found in cases with Quintero Stages 1-3 but not in those with Stage 4. CONCLUSIONS: In TTTS, UVVF is significantly higher in recipients than in their donor cotwins and the R/D-UVVF seems adequately to indicate the flow imbalance between twins, regardless of gestational age. A decrease in R/D-UVVF could be predictive of a favorable evolution following laser treatment.

Fluxo no ducto venoso e na veia cava inferior dos fetos em gestações isoimunizadas / Assess flow velocity in the ductus venosus and inferior vena cava in fetuses in isoimmunized pregnancies

OBJETIVO: Avaliar a velocidade de fluxo na veia cava inferior e no ducto venoso em fetos, nas gestações isoimunizadas. MÉTODOS: De junho de 1999 a junho de 2004, foram avaliados 61 fetos, entre 27 e 35 semanas, de gestantes portadoras de isoimunização por antígenos eritrocitários. Em todos os fetos foram avaliadas as velocidades de fluxo na veia cava inferior e no ducto venoso. Obteve-se amostra de sangue fetal para determinação dos valores da hemoglobina e calculou-se o déficit da concentração de hemoglobina. Esses fetos foram divididos em quatro grupos, de acordo com o déficit da concentração de hemoglobina: fetos não anêmicos, anêmicos leves, anêmicos moderados e anêmicos graves. Utilizou-se o teste Qui-quadrado para comparar os quatro grupos de fetos quanto à proporção da alteração da velocidade média de fluxo na veia cava inferior e no ducto venoso. RESULTADOS: A velocidade de fluxo na veia cava inferior estava alterada em 3,8 por cento dos fetos não anêmicos, em 3,1 por cento dos fetos com anemia leve, em 40 por cento dos anêmicos moderados e em 76 por cento dos fetos com anemia grave. Já a velocidade de fluxo no ducto venoso estava alterada em 7,7 por cento dos fetos não anêmicos, em 3,1 por cento dos fetos com anemia leve, em 32,5 por cento dos anêmicos moderados e em 68 por cento dos fetos com anemia grave. O valor p foi inferior a 0,001. CONCLUSÃO: Verificou-se aumento da freqüência de alteração da velocidade de fluxo na veia cava inferior e no ducto venoso à medida que a anemia se agravava.

OBJECTIVE: Ductus venosus and inferior vena cava flow velocity was assessed in fetuses in isoimmunized pregnancies. METHODS: Examination of 61 fetuses aged 27 to 35 weeks from Rh-erythrocyte antigen isoimmunized women was carried out from June 1999 to June 2004. All fetuses were submitted to the examination of ductus venosus and inferior vena cava flow velocity. Blood samples were collected to determine hemoglobin values and hemoglobin concentration deficits. Accordingly, fetuses were grouped as follows: non-anemic; mildly anemic; moderately anemic and severely anemic fetuses. Comparison of the variation of average flow velocity in the inferior vena cava and ductus venosus across the four groups was carried out using the chi-square test. RESULTS: Inferior vena cava flow velocity was found to be altered in 3.8 percent of non-anemic fetuses; in 3.1 percent of the mildly anemic, in 40.0 percent of those moderately anemic; and in 76.0 percent of the severely anemic ones. Alteration in ductus venosus flow velocity, in turn, was identified in 7.7 percent of non-anemic fetuses; 3.1 percent of mildly anemic; 32.5 percent of moderately anemic and 68.0 percent of those severely anemic. Results were statistically significant with p < 0.001. CONCLUSION: The study shows that alteration of flow velocity in the inferior vena cava and ductus venosus increased with the severity of anemia.

Ultrasound assessment of venous blood flow before and after laser therapy: approach to understanding the pathophysiology of twin-twin transfusion syndrome.

OBJECTIVE: To estimate direction and volume of blood exchange between the donor twin and recipient twin by ultrasound assessment of blood flow in the umbilical vein before and after selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS). METHODS: Forty-one TTTS patients underwent Doppler examination of the umbilical vein before and 24 h after SLPCV. The diameter and mean time-averaged velocity of the umbilical vein were estimated. Total umbilical venous flow (TUVF) was calculated as follows: TUVF (mL/min) = mean time-averaged velocity (cm/s) x mean cross-sectional area (cm2) x 60 (s). RESULTS: TUVF was significantly higher in the recipient (111.2 mL/min) than in the donor twin (44.8 mL/min) before SLPCV (P < 0.0001). However, TUVF was no different between the recipient and the donor twin after SLPCV (93.1 vs. 70.7 mL/min, recipient and donor twin, respectively, P = 0.11). The donor twin's TUVF increased after surgery (P < 0.0001), while the recipient twin's TUVF decreased (P = 0.041). The median postoperative increase in the donor twin's TUVF of 25.9 mL/min had a corresponding decrease of TUVF in the recipient twin of 18.1 mL/min (P = 0.27). CONCLUSIONS: Our data suggest that untreated TTTS is characterized by excessive umbilical venous blood flow in the recipient twin relative to the donor twin. Laser surgery results in concordant changes in umbilical venous flow in opposite directions between the donor and recipient twins, eliminating the initial imbalance. Our results lend support to the fundamental hypothesis of unbalanced blood flow exchange (net flow from donor to recipient) between monochorionic twins as the cause for TTTS and that laser surgery eliminates the pathophysiological cause.

Effects of calycosin on the impairment of barrier function induced by hypoxia in human umbilical vein endothelial cells.

The purpose of the present study was to examine the effects of calycosin, an isoflavonoid isolated from Astragali Radix, on the impairment of barrier function induced by hypoxia in cultured human umbilical vein endothelial cells. Hypoxia induced an increase in endothelial cell monolayer permeability, indicating endothelial cell barrier impairment. Endothelial barrier dysfunction induced by hypoxia was accompanied by decreases in cytosolic ATP concentration and cAMP level, the development of actin stress fibers and intercellular gap formation, suggesting that the decreases in cytosolic ATP and cAMP levels and rearrangements of F-actin could be associated with an increase in permeability of endothelial monolayers. Application of calycosin inhibited the hypoxia-induced increase in endothelial permeability in a dose-dependent fashion, which is compatible with inhibition of lactate dehydrogenase release, decrease of the fall in ATP and cAMP contents, and improvement of F-actin rearrangements. These findings indicate that calycosin protected endothelial cells from hypoxia-induced barrier impairment by increasing intracellular energetic sources and promoting regeneration of the cAMP level, as well as improving cytoskeleton remodeling.

Mechanisms of shock wave induced endothelial cell injury.

BACKGROUND AND OBJECTIVES: Medical procedures, for example, laser angioplasty and extracorporeal lithotripsy as well as high-energy trauma expose human tissues to shock waves (SWs) that may cause tissue injury. The mechanisms for this injury, often affecting blood vessel walls, are poorly understood. Here we sought to assess the role of two suggested factors, viz., cavitation or reactive oxygen species (ROS). STUDY DESIGN/MATERIALS AND METHODS: A laser driven flyer-plate model was used to expose human umbilical cord vein endothelial cell (HUVEC) monolayers to SWs or to SWs plus cavitation (SWC). Cell injury was quantified with morphometry, trypan blue staining, and release of (51)Cr from labeled HUVECs. RESULTS: HUVECs, exposed to SWs only, could not be distinguished from controls in morphological appearance or ability to exclude trypan blue. Yet, release of (51)Cr, indicated a significant cell injury (P < 0.05). HUVEC cultures exposed to SWC, exhibited cell detachment and cell membrane damage detectable with trypan blue. Release of (51)Cr was fourfold compared to SW samples (P < 0.01). Signs of cell injury were evident at 15 minutes and did not change over the next 4 hours. No protective effects of ROS scavengers were demonstrated. CONCLUSIONS: Independent of ROS, SWC generated an immediate cell injury, which can explain, for example, vessel wall perturbation described in relation to SW treatments and trauma.

Comparison of prevalence for paraumbilical vein patency in patients with viral and alcoholic liver cirrhosis.

OBJECTIVES: The patent paraumbilical vein (PUV) is a venous collateral that is often found in patients with cirrhosis and portal hypertension. It can be effectively demonstrated by conventional ultrasonography (US). We conducted this prospective study to elucidate the prevalence and etiology of PUV patency for cirrhotic patients. METHODS: From August, 1997, to July, 1998, one of the authors (S.-N.L.) observed PUV patency for all cirrhotic patients during routine upper abdominal US examination. All cirrhotic patients diagnosed with portal hypertension were further analyzed. Portal hypertension was diagnosed by sonographic evidence of splenomegaly or ascites, or endoscopic varices. Cases presenting with hepatocellular carcinoma and sonographic evidence of prehepatic portal hypertension were excluded. Once a PUV patency with a diameter of > or = 3 mm was suspected based on conventional US, it was confirmed by color Doppler US. Of the 493 cirrhotic patients examined, 252 with portal hypertension and without hepatoma were enrolled in this study. RESULTS: Significant PUV patency was detected in 11.1% of the enrolled patients (28 of 252). With univariate analysis, a significantly higher prevalence was demonstrated for alcoholic patients (p < 0.0001), whereas prevalence was relatively low for those with chronic hepatitis B or C infection (p = 0.0159). A trend toward increased prevalence was noted with Child-Pugh classification (p = 0.001). Furthermore, a higher prevalence was noted in younger cirrhotic patients (p = 0.0037). Alcoholism was still a significant factor despite adjustment of Child-Pugh classification using multiple logistic regression, (OR = 3.88, 95% CI = 1.34-8.55). CONCLUSION: A significantly higher prevalence of PUV patency was demonstrated for patients with alcohol-induced liver cirrhosis in comparison to those with postviral cirrhosis.