Pulmonary Vein Flow Impedance: An Early Predictor of Cardiac Dysfunction in Intrauterine Growth Restriction.

INTRODUCTION: In intrauterine growth restriction (IUGR), increased uteroplacental vascular impedance contributes to preferential flow to left ventricle (LV), with consequent alteration of its compliance and increased left atrial (LA) pressure. Pulmonary vein pulsatility index (PVPI) reflects the increased impedance to LA filling and could be used as a cardiac monitoring parameter in IUGR. MATERIAL AND METHODS: A total of 27 IUGR fetuses (group 1), 28 fetuses with appropriate growth for gestational age from hypertensive mothers (group 2), and 28 controls (group 3) were studied. Pulsatility indices (PIs) of pulmonary veins and ductus venosus were calculated by Doppler echocardiography. Obstetric ultrasound was used to assess the PIs of uterine, umbilical, and middle cerebral arteries. Statistical analysis used analysis of variance, post-hoc Tukey, and Pearson's tests. RESULTS: Mean PVPI was higher in IUGR group (1.27 ± 0.39) when compared to groups 2 (1.02 ± 0.37; p = 0.01) and 3 (0.75 ± 0.12; p < 0.001). In group 2, moderate correlation between PVPI and ductus venosus pulsatility index (DVPI) was found but not between PVPI and cerebroplacental ratio (CPR). DISCUSSION: Higher PVPI in IUGR reflects decreased LV compliance and altered LA dynamics. As LV dysfunction precedes right ventricle, our results suggest that PVPI could be an early echocardiographic parameter of fetal diastolic function in IUGR.

Mechanisms of endothelial cell dysfunction in cystic fibrosis.

Although cystic fibrosis (CF) patients exhibit signs of endothelial perturbation, the functions of the cystic fibrosis conductance regulator (CFTR) in vascular endothelial cells (EC) are poorly defined. We sought to uncover biological activities of endothelial CFTR, relevant for vascular homeostasis and inflammation. We examined cells from human umbilical cords (HUVEC) and pulmonary artery isolated from non-cystic fibrosis (PAEC) and CF human lungs (CF-PAEC), under static conditions or physiological shear. CFTR activity, clearly detected in HUVEC and PAEC, was markedly reduced in CF-PAEC. CFTR blockade increased endothelial permeability to macromolecules and reduced trans­endothelial electrical resistance (TEER). Consistent with this, CF-PAEC displayed lower TEER compared to PAEC. Under shear, CFTR blockade reduced VE-cadherin and p120 catenin membrane expression and triggered the formation of paxillin- and vinculin-enriched membrane blebs that evolved in shrinking of the cell body and disruption of cell-cell contacts. These changes were accompanied by enhanced release of microvesicles, which displayed reduced capability to stimulate proliferation in recipient EC. CFTR blockade also suppressed insulin-induced NO generation by EC, likely by inhibiting eNOS and AKT phosphorylation, whereas it enhanced IL-8 release. Remarkably, phosphodiesterase inhibitors in combination with a ß2 adrenergic receptor agonist corrected functional and morphological changes triggered by CFTR dysfunction in EC. Our results uncover regulatory functions of CFTR in EC, suggesting a physiological role of CFTR in the maintenance EC homeostasis and its involvement in pathogenetic aspects of CF. Moreover, our findings open avenues for novel pharmacology to control endothelial dysfunction and its consequences in CF.

Phosphodiesterase type 4 blockade prevents platelet-mediated neutrophil recruitment at the site of vascular injury.

OBJECTIVE: Platelet-neutrophil interactions play a key role in cardiovascular disease and inflammatory processes. Src family kinases mediate P-selectin glycoprotein ligand-1-Mac-1 cross talk necessary for firm platelet-neutrophil adhesion. Because Src family kinase activity can be regulated by cAMP-dependent pathways, in this work, we evaluated the role of phosphodiesterases in the signaling events that are required to sustain platelet-neutrophil interactions and neutrophil recruitment at the site of vascular injury. APPROACH AND RESULTS: In neutrophils exposed to P-selectin, selective phosphodiesterase 4 (PDE4) inhibition prevented Src family kinase-mediated phosphorylation of the proline-rich tyrosine kinase 2 on Tyr579/Tyr580. The effects of PDE4 inhibition required protein kinase A, likely through protein kinase A-mediated activation of COOH-terminal Src kinase, a major negative regulator of Src family kinases. PDE4, but not other phosphodiesterase inhibitors, reduced platelet-neutrophil conjugates as well as neutrophil firm adhesion on spread platelets under flow conditions. The effect of PDE4 inhibition on neutrophil adhesion was primarily mediated by downregulation of P-selectin-induced activation of Mac-1. In a murine model of endovascular injury, selective inhibition of PDE4 significantly reduced neutrophil recruitment at the site of vascular damage. CONCLUSIONS: This study identifies PDE4 as a central node in the signaling network that mediates platelet-neutrophil adhesion and suggests that pharmacological inhibition of PDE4 may represent a novel therapeutic avenue for the treatment of cardiovascular disease.

Lengthening the time intervals between doses of biological agents in psoriatic arthritis patients: A single-center retrospective study.

Anti-tumor necrosis factor (TNF) alpha therapy has changed the course of psoriatic arthritis (PsA), but clinical experience about lengthening of time intervals between drug administrations is still limited. The aims of the study were to evaluate: (1) the long-term efficacy (over a 4-year period) of etanercept/adalimumab in a subset of PsA patients who did not require switches; and (2) the progressive lengthening of time intervals between treatments in patients who achieved minimal disease activity (MDA). PsA outpatients attending the Rheumatology Clinic-University of Padova who took a single anti-TNF agent (etanercept/adalimumab) for a 4-year period were studied. Therapy efficacy was assessed using clinical, biochemical, and disease activity (DA) indexes. The intervals between treatments were empirically and progressively lengthened after MDA was reached and maintained. One hundred and forty-one patients (mean age, 51.22 ± 12.34 years; mean disease duration, 12.1 ± 8.42 years) treated with etanercept/adalimumab (47.5% and 52.5%, respectively) were studied. DA indexes showed a marked, persistent improvement in all the patients throughout 4 years. The interval between injections could be extended in 46.1% of the patients (35% for adalimumab, 58% for etanercept) without provoking relapses. The mean therapy interval at the end of the study period was 3.12 weeks for adalimumab 40 mg (with respect to 2 weeks) and 2.75 weeks for etanercept 25 mg (with respect to 0.5 weeks). The new therapy timetable also led to cost savings. In conclusion, lengthening the time intervals between injections of anti-TNF agents in PsA patients who reach MDA is safe, effective, cost-effective, and facilitates patient compliance.

Dynamics of pulmonary venous flow in fetuses with intrauterine growth restriction.

OBJECTIVE: To test the hypothesis that the pulmonary vein pulsatility index (PVPI) is higher in fetuses with growth restriction (IUGR) than in normal fetuses. METHODS: Twenty-two fetuses with IUGR and twenty-one (21) fetuses with appropriate growth for gestational age from healthy mothers were studied. PVPI was calculated by Doppler echocardiography [maximal velocity (systolic or diastolic peak) - pre-systolic peak / mean velocity]. Obstetric ultrasound was used to assess fetal biometry and Doppler to assess the uterine, umbilical and middle cerebral arteries PI. Statistical analysis used t test and Pearson's correlation. RESULTS: Mean gestational age was 31.5 +/- 2.1 weeks in the control group and 31.4 +/- 3.1 weeks in IUGR (P = 0.91). The PI of uterine and umbilical arteries were higher in IUGR than in controls (P < 0.001). Mean PVPI in IUGR fetuses was 1.31 +/- 0.41, and in controls it was 0.83 +/- 0.11 (P < 0.001). CONCLUSION: The pulsatility index of pulmonary venous flow in fetuses with growth restriction is higher than in normal fetuses, probably as a result of left atrial dynamics alteration secondary or not to fetal left ventricular diastolic dysfunction. © 2014 John Wiley & Sons, Ltd.

Development and validation of a food frequency questionnaire for consumption of polyphenol-rich foods in pregnant women.

Previous studies have shown that maternal consumption of polyphenol-rich foods after the third trimester of pregnancy may interfere with the anatomical and functional activity of the fetal heart as, to our knowledge, there are no validated instruments to quantify total polyphenols in pregnant women. The aim of this study was evaluate the reproducibility and validity of a food frequency questionnaire (FFQ), with 52 items, to assess the intake of polyphenol-rich foods in pregnant women in Brazil. This cross-sectional study included 120 pregnant women who participated in nutritional interviews in two moments. The intake of polyphenols estimated by the developed FFQ was compared with the average of two 24-h recalls (24HR), with the average intake measured by a 3-day food diary (D3days) and with the urinary excretion of total polyphenols. The triangular method was applied to calculate Pearson's correlation coefficients, intraclass correlation and Bland-Altman plots for the FFQ, using an independent biochemical marker, in addition to classification by quarters of consumption. The questionnaires were log transformed, adjusted for body mass index and gestational age. The adjustment for energy was applied only of 24HR and D3days. Analysis of the reproducibility between the FFQ showed a very high correlation (r = 0.72; P < 0.05). A low but significant association was observed between the FFQ and urinary excretion (0.23; P = 0.01). The association between the dietary survey methods was moderate to very high (r = 0.36 to r = 0.72; P < 0.001). In conclusion, this questionnaire showed reproducibility and validity for the quantification of consumption of total polyphenols in pregnant women.

Estimation of fluid volumes in hemodialysis patients: comparing bioimpedance with isotopic and dilution methods.

Both single-frequency bioimpedance and multiple-frequency spectroscopy are equally accurate in measuring total-body water and intracellular fluid. Estimates are consistent at a population level but not at the individual level, because of wide limits of agreement. There is no real 'gold standard' method providing estimates with absolute accuracy (in liters). Bioelectrical impedance vector analysis allows comparison of the actual body impedance with that of the reference population (in Ω/m). Hemodialysis prescription can be optimized with the use of this feedback.

The relationship between the Spine Deformity Index, biochemical parameters of bone metabolism and vascular calcifications: results from the Epidemiological VERtebral FRACtures iTalian Study (EVERFRACT) in dialysis patients.

BACKGROUND: The Spine Deformity Index (SDI) is a measure of vertebral fractures (VFs), providing information on both their number and severity. METHODS: We evaluated the relationships between SDI and clinical, biochemical and arterial calcification parameters in 387 hemodialysis (HD) patients. VFs, assessed by quantitative vertebral morphometry, and vascular calcifications were identified in the same lateral spinal X-ray. To improve the detection of fracture severity, we created a corrected SDI (c-SDI), by dividing SDI for the number of VFs. We assessed routine biochemistry, bone-Gla-protein (BGP), undercaboxylated BGP (ucBGP), and matrix-Gla-protein (MGP). RESULTS: VFs prevalence was 55.3%. HD patients with a SDI >1 were more frequently males (p<0.05), and had lower BGP (p<0.01). Patients with a c-SDI >1 had higher LDL-cholesterol (p<0.05) and lower ucBGP (p<0.05) and MGP (p<0.05). Calcifications of the abdominal aorta (AAoC) were more frequent in patients with SDI >1 (p<0.05) and with c-SDI >1 (p<0.05). Multivariate logistic regression showed that male sex (OR 1.86, CI 1.20-2.91), age (OR 1.03, CI 1.01-1.05) and albumin ≥3.5 g/dL (OR 0.54, CI 0.31-0.93) were predictors of a SDI >1. Age (OR 1.05, CI 1.03-1.07), LDL-cholesterol (OR 1.74, CI 1.04-2.92) and ucBGP (OR 0.35, CI 0.18-0.70) were associated with c-SDI >1. CONCLUSIONS: We conclude that the severity of VFs was associated with age, atherogenic factors and bone metabolism markers.

Copeptin decrease from admission to discharge has favorable prognostic value for 90-day events in patients admitted with dyspnea.

BACKGROUND: With patients referred to emergency departments (EDs) for acute dyspnea, emergency physicians should consider all possible diagnoses and assess patients' risk stratification. Copeptin has been shown to have prognostic power for subsequent events, such as death and rehospitalization in patients admitted for dyspnea. The aim of this study was to investigate prognostic role of copeptin variations during hospitalization in patients admitted for dyspnea. METHODS: We conducted a prospective, multicentric, observational study in acute dyspneic patients in three ED centers in Italy. Clinical data and copeptin assessments were performed at admission, and at discharge. A 90-day follow-up was performed. RESULTS: A total of 336 patients were enrolled, and on the basis of final diagnosis distinguished into two groups: acute heart failure and no acute heart failure. Compared to a control group, in all studied population copeptin values at admission resulted in a significantly (p<0.001) higher median (maximum-minimum): 31 (0-905) versus 8 (0-13) pmol/L. Median copeptin value at admission was 42 (0-905) pmol/L in acute heart failure patients and 20 (0-887) pmol/L in no acute heart failure, respectively (p<0.001). In all studied patients and in each group copeptin at admission and discharge showed significant predictive value for 90-day events (p<0.001). Furthermore, in all patients population and in both groups Δ copeptin values from admission to discharge also showed significant predictive value for 90-day events (p<0.001). CONCLUSIONS: In patients admitted for acute dyspnea, admission, discharge and Δ copeptin variations have significant prognostic value from subsequent 90-day death and rehospitalization.

Nitric oxide and reactive species are modulated in the polyphenol-induced ductus arteriosus constriction in pregnant sheep.

OBJECTIVE: Because we have previously demonstrated the relation between polyphenol-rich foods (PRF) consumption and ductus arteriosus constriction, in this work, pregnant sheep were submitted to oral PRF intake for 14 days to understand how this process occurs. Fetal Doppler echocardiography, oxidative and inflammatory biomarkers and total polyphenol excretion were evaluated. RESULTS: The high polyphenol intake induced ductus arteriosus constriction by 71.6% increase in systolic (P = 0.001) and 57.8% in diastolic velocities (P = 0.002), and 18.9% decrease in pulsatility index (P = 0.033), along with 1.7-fold increase in total polyphenol excretion, 2.3-fold decrease in inflammatory mediator nitric oxide and following redox status changes (mean ± standard deviation): higher protein carbonyls (1.09 ± 0.09 and 1.49 ± 0.31), catalase (0.69 ± 0.39 and 1.44 ± 0.33) and glutathione peroxidase (37.23 ± 11.19 and 62.96 ± 15.03) in addition to lower lipid damage (17.22 ± 2.05 and 12.53 ± 2.11) and nonprotein thiols (0.11 ± 0.04 and 0.04 ± 0.01) found before and after treatment, respectively. Ductal parameters correlated to NOx , catalase, glutathione peroxidase and protein carbonyl. CONCLUSION: Our results highlight the need to reduce maternal PRF intake in late pregnancy to prevent fetal duct constriction through NO-mediated vasoconstrictive action of polyphenols.

Differentiation of cardiac and noncardiac dyspnea using bioelectrical impedance vector analysis (BIVA).

BACKGROUND: There is no gold standard for the differential diagnosis of acute dyspnea despite the usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and lung ultrasound. No study has evaluated the contribution of bioelectrical impedance vector analysis (BIVA) in discriminating between cardiac and noncardiac dyspnea. We sought to determine whether a relationship exists between ultrasound detection of lung congestion, NT-proBNP, and BIVA in patients with acute dyspnea. METHODS AND RESULTS: Eligible patients were between 50 and 95 years, with an estimated glomerular filtration rate of ≥30 mL min(-1) 1.73 m(-2), who presented to an emergency department with dyspnea. Dyspnea was classified by reviewers blinded to BIVA as cardiac or noncardiac based on physical examination, electrocardiogram, chest X-ray, NT-proBNP, and B-lines of lung congestion on ultrasound. Overall, 315 patients were enrolled (median age 77 years, 48% male). An adjudicated diagnosis of cardiac dyspnea was established in 169 (54%). Using BIVA, vector positions below -1 SD of the Z-score of reactance were associated with peripheral congestion (χ(2) = 115; P < .001). BIVA measures were reasonably accurate in discriminating cardiac and noncardiac dyspnea (69% sensitivity, 79% specificity, 80% area under the receiver operating characteristic curve). CONCLUSIONS: In patients presenting with acute dyspnea, the combination of BIVA and lung ultrasound may provide a rapid noninvasive method to determine the cause of dyspnea.

Effects of estrogen on endothelial prostanoid production and cyclooxygenase-2 and heme oxygenase-1 expression.

We studied the effects of 17ß-estradiol (E2) (10, 40 nM) on 2 vasoprotective pathways, i.e. cyclooxygenase-2 (COX-2)-dependent prostanoids and the antioxidant heme oxygenase-1 (HO-1), in human umbilical vein endothelial cells (HUVEC) exposed for 6h to steady laminar shear stress (LSS, 10 dyn/cm²), characteristic of atherosclerotic lesion-protected areas. COX-2 was induced by LSS versus static condition (SC). E2 did not significantly affect COX-2 expression in HUVEC cultured in SC or exposed to LSS. Prostacyclin (PGI2) and prostaglandin (PG)E2 were induced while PGF(2α) was reduced by LSS. E2 caused no effect or a small reduction of prostanoid biosynthesis. In HUVEC cultured in SC or exposed to LSS, E2 10 nM caused a comparable HO-1 induction (35-45%) while E2 40 nM was 5-fold more potent in LSS-exposed HUVEC than in SC (290% and 58%, respectively). PGI2 receptor antagonist RO3244794 did not affect HO-1 induction by E2. In conclusion, E2 may restrain oxidant stress in the endothelium through HO-1 induction by a mechanism independent on PGI2 signaling.

Fetal ductal constriction caused by maternal ingestion of green tea in late pregnancy: an experimental study.

OBJECTIVES: The aim of this study was to test the hypothesis that experimental maternal intake of green tea in late pregnancy causes fetal ductus arteriosus constriction, probably because of prostaglandin inhibition. METHODS AND RESULTS: Twelve fetal lambs (pregnancy > 120 days) were assessed before and after maternal administration of green tea (n = 8) or water (n = 4; controls) as the only source of liquid. After 1 week, echocardiography showed signs of constriction of the ductus arteriosus in all fetuses from mothers ingesting green tea, with increase in mean systolic velocity(from 0.70 ± 0.19 m/s to 0.92 ± 0.15 m/s, 31.4%, p = 0.001) and mean diastolic velocity (0.19 ± 0.05 m/s to 0.31 ± 0.01 m/s, 63.1%, p < 0.001), decrease of pulsatility index (2.2 ± 0.4 to 1.8 ± 0.3, 22.2%, p = 0.003) and increase of mean right ventricular/left ventricular diameter ratio (0.89 ± 0.14 to 1.43 ± 0.23, 60.6%, p < 0.001). In the four control fetuses, there were no significant changes. All lambs exposed to green tea also showed at autopsy dilated and hypertrophic right ventricles, which was not present in control fetuses. Histological analysis showed a significantly larger mean thickness of the medial avascular zone of the ductus arteriosus in fetuses exposed to green tea than in controls (747.6 ± 214.6 µm vs 255.3 ± 97.9 µm, p < 0.001). CONCLUSIONS: This study in fetal lambs shows a cause and effect relationship between experimental maternal exposure of green tea and fetal ductus arteriosus constriction in late pregnancy.

Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and {beta}2 integrin-dependent cell clearance program.

Activated platelets express ligands, which are recognized by counterreceptors on neutrophils. Here, we show that the ensuing cell-to-cell interaction programs neutrophil phagocytic function, resulting in activated platelet clearance. Neutrophils that have internalized platelets circulate in the blood of patients with acute myocardial infarction, and the extent of platelet clearance correlates with expression of platelet activation, including P-selectin. Activated platelets injected intravenously in experimental animals are detectable in circulating neutrophils 60 minutes after, and within 3 hours, more than 70% circulating neutrophils have internalized platelets. Platelet clearance comprises 2 events: adhesion to neutrophils, which requires divalent cations and depends on P-selectin, on the P-selectin glycoprotein ligand-1 (PSGL-1), and on the CD11b/CD18 beta2 integrin; and internalization, which is abrogated by the phosphatidylserine-binding protein annexin A5. Adhesion to platelets causes neutrophil degranulation and is blocked by antibodies specific for P-selectin and PSGL-1, either in a synthetic medium in vitro or in the whole blood, therefore in the presence of a physiologic array of plasma cofactors and opsonins. The data suggest that the interaction between circulating platelets and neutrophils influences innate immune functions, possibly contributing to regulate vascular inflammation.

Induction of prostacyclin by steady laminar shear stress suppresses tumor necrosis factor-alpha biosynthesis via heme oxygenase-1 in human endothelial cells.

Cyclooxygenase (COX)-2 is among the endothelial genes upregulated by uniform laminar shear stress (LSS), characteristically associated with atherosclerotic lesion-protected areas. We have addressed whether the induction of COX-2-dependent prostanoids in endothelial cells by LSS plays a role in restraining endothelial tumor necrosis factor (TNF)-alpha generation, a proatherogenic cytokine, through the induction of heme oxygenase-1 (HO)-1, an antioxidant enzyme. In human umbilical vein endothelial cells (HUVECs) exposed to steady LSS of 10 dyn/cm(2) for 6 hours, COX-2 protein was significantly induced, whereas COX-1 and the downstream synthases were not significantly modulated. This was associated with significant (P<0.05) increase of 6-keto-prostaglandin (PG)F(1alpha) (the hydrolysis product of prostacyclin), PGE(2), and PGD(2). In contrast, TNF-alpha released in the medium in 6 hours (3633+/-882 pg) or detected in cells lysates (1091+/-270 pg) was significantly (P<0.05) reduced versus static condition (9100+/-2158 and 2208+/-300 pg, respectively). Coincident induction of HO-1 was detected. The finding that LSS-dependent reduction of TNF-alpha generation and HO-1 induction were abrogated by the selective inhibitor of COX-2 NS-398, the nonselective COX inhibitor aspirin, or the specific prostacyclin receptor (IP) antagonist RO3244794 illuminates the central role played by LSS-induced COX-2-dependent prostacyclin in restraining endothelial inflammation. Carbacyclin, an agonist of IP, induced HO-1. Similarly to inhibition of prostacyclin biosynthesis or activity, the novel imidazole-based HO-1 inhibitor QC15 reversed TNF-alpha reduction by LSS. These findings suggest that inhibition of COX-2-dependent prostacyclin might contribute to acceleration of atherogenesis in patients taking traditional nonsteroidal antiinflammatory drugs (NSAIDs) and NSAIDs selective for COX-2 through downregulation of HO-1, which halts TNF-alpha generation in human endothelial cells.

Determinants of circulating asymmetric and symmetric dimethylarginines in patients evaluated for acute dyspnea.

BACKGROUND: The relationship between asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) plasma concentrations and acute heart failure is unknown. We evaluated ADMA and SDMA in patients with acute dyspnea. METHODS: We studied 57 dyspneic subjects (50-95 years), with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m², presenting to the emergency department. Troponin I, N terminal-proBNP (NT-proBNP), ADMA, and SDMA were measured. Electrocardiogram, chest X-ray and lung ultrasound were performed. Patients were classified into cardiogenic dyspnea and non-cardiogenic dyspnea, and were also classified on the basis of renal function according to their eGFR. RESULTS: Two-way analysis of variance demonstrated that ADMA and SDMA did not differ for type of dyspnea, but increased in renal dysfunction. NT-proBNP significantly increased both in cardiogenic dyspnea and renal dysfunction. Multiple regression analysis demonstrated that after adjustment for troponin and dyspnea, the only variables which significantly correlated with SDMA plasma concentrations were renal function (ß = -0.47, p < 0.001) and NT-proBNP (ß = 0.28, p = 0.02). CONCLUSIONS: Neither type of dimethylarginine showed cardiogenic dyspnea to be a determinant for plasma concentrations. Renal dysfunction was a confounder for both ADMA and SDMA.

Aortic isthmus blood flow in fetuses of diabetic mothers.

OBJECTIVE: To test the hypothesis that the aortic isthmus flow index (IFI) is lower in fetuses of diabetic mothers than in fetuses of nondiabetic mothers. STUDY DESIGN: We performed a cross-sectional observational study to assess the IFI in fetuses, with (n = 13) and without (n = 37) myocardial hypertrophy, of mothers with diabetes mellitus and in fetuses of nondiabetic mothers (n = 23). Analysis of variance and Tukey test were used to assess differences among the groups. RESULTS: There were no differences in maternal or gestational age among the groups. In fetuses of diabetic mothers, the mean IFI in fetuses with myocardial hypertrophy was 1.19 ± 0.06, and in fetuses without it was 1.18 ± 0.09. The mean IFI in fetuses of nondiabetic mothers was 1.32 ± 0.07 (P < 0.001). CONCLUSIONS: The IFI in fetuses of diabetic mothers is lower than in fetuses of nondiabetic mothers, possibly as a result of a decreased left ventricular compliance.

Influence of fetal respiratory movements on left atrial functional status.

OBJECTIVE: Because fetal respiratory movements increase left ventricular compliance, we hypothesized that the left atrial shortening fraction increases during fetal respiratory motions. METHODS: A group of 26 normal fetuses with gestational ages between 28 and 38 weeks were assessed in a prospective cross-sectional study. Left atrial telesystolic and presystolic diameters were measured during apnea and after five consecutive respiratory movements. Left atrial shortening fraction was obtained by the ratio: [maximal left atrium diameter (telesystolic) - minimal left atrium diameter (presystolic)]/maximal left atrium diameter (telesystolic). The mean of three measurements were considered. Two-tailed Student's t-test was used. RESULTS: Mean gestational age was (mean ± SD) 30.7 ± 2.8 weeks. Mean left atrial telesystolic diameter in apnea was 10.6 ± 0.7 mm and during respiratory movements it was 10.5 ± 1.1 mm (p = 0.98). Presystolic left atrial diameter was 5.2 ± 0.1 mm in apnea and 4.4 ± 1.3 mm during respiratory movements (p < 0.001). Left atrial shortening fraction was 0.50 ± 0.05 in apnea and 0.58 ± 0.13 during respiratory movements (p < 0.001). CONCLUSION: Left atrial shortening fraction is higher during respiratory movements as a result of increased left ventricular compliance and consequent optimization of left atrial functional status.

Reduction of hyperphosphatemia is related with the reduction of C-reactive protein in dialysis patients. Study in sevelamer-resistant dialysis patients treated with chitosan chewing gum as salivary phosphate binder.

BACKGROUND: In end-stage renal disease (ESRD) hyperphosphatemia associates with vascular calcifications and cardiovascular events derived from endothelial dysfunction. In dialysis patients, C-reactive protein (CRP), a marker of inflammation, associates with cardiovascular mortality. Increased PO(4) concentration impairs endothelial integrity via induction of oxidative stress, and sevelamer, a phosphate binder, showed anti-inflammatory effect reducing CRP, which paralleled PO(4) reduction. To give support to a direct proinflammatory role of hyperphosphatemia "per se," we have considered previously studied dialysis patients with sevelamer-"resistant" hyperphosphatemia, who were treated with a chitosan-loaded chewing gum, as salivary phosphate binder, in addition to sevelamer, reduced serum PO(4) to normal, to retrospectively evaluate their CRP and the relationship with hyperphosphatemia and calcium × phosphate (Ca × PO(4)) product. PATIENTS AND METHODS: High sensitive (hs) CRP of 13 previously studied hemodialysis patients with sevelamer-resistant hyperphosphatemia was evaluated with immunonephelometry. RESULTS: Chitosan chewing gum use reduced hsCRP (from 1.38 ± 0.61 to 0.39 ± 0.16 mg/L after the gum, p < 0.0002), which returned to baseline after 4 weeks from gum discontinuation (1.25 ± 0.41). hsCRP reduction paralleled serum PO(4) reduction: from 7.60 ± 0.91 mg/dL to 5.18 ± 0.73 (after the gum) (p < 0.00001), returning to baseline (7.55 ± 0.75) after gum discontinuation. hsCRP reduction directly correlated with PO(4) reduction (p = 0.029). CONCLUSION: The relationship in sevelamer-resistant dialysis patients between the reduction of serum PO(4), induced by the chitosan-loaded chewing gum, and CRP reduction supports also in humans a proinflammatory role of hyperphosphatemia "per se" derived from "in vitro" studies. This further contributes to the high cardiovascular risk of ESRD patients making their serum phosphate in the normal range of vital importance.