- Email: [email protected]
P76 Angiogenic and anti-angiogenic factors determination in early-onset and late-onset preeclampsia
S62
Poster Presentations / Pregnancy Hypertension 1, Supplement 1 (2010) S43–S76
(25-75 percentile): 76.5 (70.3-82.9) % and 59.0 (51.7-64.4) %, respectively). Furthermore, CD4+ helper and CD8+ cytotoxic T cells showed a similar pattern of intracellular galectin-1 expression in normal pregnancy. However, the proportion of galectin-1-expressing peripheral blood T (both helper and cytotoxic) and NK cells was markedly decreased in preeclampsia (for T cells: 30.6 (21.3-34.4) %, p<0.001; for NK cells: 42.9 (32.0-61.9) %, p<0.001). Conclusions: The majority of circulating NK and – to a lesser extent – T (helper and cytotoxic) cells shows intracellular galectin-1 expression in normal pregnancy. In preeclampsia, the proportion of galectin-1-positive T (both helper and cytotoxic) and NK cells in the peripheral blood is markedly decreased, which might contribute to the development of the generalized intravascular inflammatory reaction characteristic of the maternal syndrome of the disease.
P73 Structure and function of posterior cerebral arteries in a preeclampsia rat model Marjon Wiegman 1 , Anne Marijn van der Graaf 1 , Gerda Zeeman 1 , Jan Aarnoudse 1 , Rob Henning 2 , Hendrik Buikema 2 , Marijke Faas 3 . 1 Department of Obstetrics & Gynecology, University Medical Center Groningen, The Netherlands; 2 Department of Clinical Pharmacology, University Medical Center Groningen, The Netherlands; 3 Department of Medical Biology and Pathology, University Medical Center Groningen, The Netherlands Background: Eclampsia is thought to be a form of the posterior reversible encephalopathy syndrome, in which an acute rise in blood pressure causes breakthrough of autoregulation, hyperperfusion, blood-brain barrier disruption and cerebral edema formation. Because of the central role of the cerebrovasculature in the pathophysiology of eclampsia, this study assesses the effect of preeclampsia on myogenic activity and remodeling of cerebral arteries in the endotoxin-induced preeclampsia rat model. Methods: Nonpregnant (NP) and late-pregnant (LP; day 20) Wistar rats were infused with either saline (NP-Saline, n=9; LP-Saline, n=9) or 1.0 ug/kg body weight endotoxin (NP-endotoxin, n=7; LP-endotoxin, n=10) on day 14 of pregnancy or 6 days before sacrifice in NP animals. Third-order branches of the posterior cerebral artery from these animals were mounted in an arteriograph chamber to measure myogenic tone at intravascular pressures from 50-175 mmHg. Pressure of forced dilatation was determined using repeated-measures ANOVA. Passive measurements, i.e. passive diameter, wall thickness, and wall-to-lumen ratio, were obtained by adding papaverine. Two-way ANOVA with Bonferroni post-test was used to determine the effect of pregnancy and endotoxin on myogenic tone and passive measurements. Results: LP-endotoxin animals underwent forced dilatation at a lower pressure compared to the other three groups, i.e. between 125-150 mmHg for LP-endotoxin compared to 150-175 mmHg in the other groups. Also, LPendotoxin animals showed diminished myogenic tone at 175 mmHg versus NP-endotoxin (18.0±4.6 vs. 39.5±4.8%; p<0.05). No other differences in myogenic tone were found between the groups. Passive measurements were similar for all groups. Conclusion: These results suggest that no protective remodeling occurred in response to experimental mild preeclampsia. However, in LP-endotoxin animals pressure of forced dilatation was decreased compared to the other groups. This suggests that mild preeclampsia, but not uncomplicated pregnancy, may predispose the brain to autoregulatory breakthrough and development of eclampsia when blood pressure is elevated.
exposed only to systemic factors (n= 14). Controls were age-matched (0.80.9 gestation) Control Gravid (C-G; n=10) and Control Non-gravid (C-NG; n= 13; Follicular and Luteal) animals. UBF, SS, UA structure and function were measured. SS = 4 UBF * Viscosity/πr 3 ; viscosity @ shear rates > 60/sec. Impedance was measured using simultaneous UBF and perfusion pressure @ 120Hz. Asymmetric IUGR was observed with uterine space restriction. UBF and SS were greater in UP-G & C-G associated with higher oxygen delivery/extraction. UA endothelial eNOS and NO was elevated 2-4 fold in UP-G & C-G vs. UP-NG & C-NG. We observed normal vascular remodeling with gestation; vascular impedance metrics, structure, circumferential and longitudinal mechanical properties of UAs: UP-NG = C-NG and from UP-G = C-G. Furthermore, UP-NG UBF and SS were similar to Follicular-C-NG sheep and were greater then Luteal-C-NG. Isolating the non-gravid horn vasculature from SS rises and placental factors throughout gestation fully abrogated functional mechanical and structural remodeling of UAs: i.e. Diameter, Circumferential and Longitudinal Green Strain and Cauchy Stress, as well as Circumferential Incremental Elastic Modulus. Thus local, not systemic, placental factors during gestation are responsible for elevations in UA SS and remodeling. Formation of low resistance, uteroplacental vascular beds during pregnancy are a key element to inducing UA remodeling through elevated flow, eNOS and SS. NIH HL49210, HD38843, HL87144.
P75 Visual field defects after eclampsia Marjon Wiegman 1 , Anne Marijn van der Graaf 1 , Nina Roos 1 , Nomdo Jansonius 2 , Jan Aarnoudse 1 , Gerda Zeeman 1 . 1 Department of Obstetrics & Gynaecology, University Medical Center Groningen, The Netherlands; 2 Department of Ophthalmology, University Medical Center Groningen, The Netherlands Background: Eclampsia is thought to be a form of posterior reversible encephalopathy syndrome (PRES) in which cerebral edema formation leads to neurological symptoms, such as visual disturbances. During the acute phase of PRES, the most common visual abnormality is transient cortical blindness but homonymous anopia, visual neglect, and blurred vision can also occur. The reversibility of PRES has been questioned. In previous studies, eclamptic women showed persistent cerebral white matter lesions on MRI on both short and long term follow-up. In general, eclamptic patients regain their vision. However, incidentally visual field loss has been described to persist years after the acute phase and is thought to be related to persistent lesions or infarctions in the visual cortex. It is possible that unconscious homonymous anopia is present in formerly eclamptic patients, which is the subject of the current study. Methods: To assess the presence of visual field defects, 36 formerly eclamptic women, who experienced eclampsia between 1988 and 2008 underwent standard automatic perimetry using a Humphrey Field Analyzer with a 52-point grid covering the central field with a radius of 24 degrees and a threshold-related supra-threshold testing strategy. In case of repeated abnormal visual field testing the participant was referred for a formal full ophthalmologic examination to rule out other pathology. Results: Mean age and elapsed time (± standard deviation) since eclampsia was 40.8±7.4 and 10.7±5.3 years, respectively. Long term MRI follow up was available for 24 participants, of which 11 demonstrated cerebral white matter lesions. None of the 36 formerly eclamptic women demonstrated visual field loss. Conclusion: Although a substantial part of formerly eclamptic patients showed persistent cerebral lesions on MRI-scans, these lesions do not seem to induce visual field defects in this cohort. However, a larger group needs to be tested to definitely confirm these results.
P74 Local uteroplacental factors increase uterine blood flow (UBF) and shear stress (SS) in association with structural and mechanical indices, vascular impedance metrics, and eNOS/NO levels 1
1
1
1
Ronald Magness , Benjamin Sprague , Daniel Henao , Jayanth Ramadoss , Jill Koch 1 , Naomi Chesler 2 . 1 University of Wisconsin-Madison, USA; 2 University of Wisconsin, USA Vascular remodeling facilitates rises in UBF needed for fetal growth. Remodeling of the uterine vasculature normalize SS. Anatomically space-restricted uterine cavities are associated with preeclampsia/IUGR. We developed an ovine surgical model to create a unicornuate/didelphic uterus to study space restriction and uterine artery (UA) adaptations. Prior to conception (>60d), inter-corneal connections were severed, one horn was ligated leaving the ipsilateral gravid horn (UP-G) vasculature locally exposed to SS and uteroplacental factors and the contralateral non-gravid (UP-NG) horn vasculature
P76 Angiogenic and anti-angiogenic factors determination in early-onset and late-onset preeclampsia Maria Terezinha Peracoli 1 , Vera Therezinha Borges 2 , Camila Ferreira Bannwart 1 , Leonardo Teixeira Medeiros 1 , Ingrid Cristina Weel 1 , Mariana Romao 1 , Erika Nakaira-Takahagi 1 , José Carlos Peracoli 2 . 1 Institute of Biosciences/Sao Paulo State University, Botucatu, Sao Paulo, Brazil; 2 Botucatu Medical School/Sao Paulo State University, Botucatu, Sao Paulo, Brazil Background: Changes in circulating angiogenic factors have been implicated in the pathogenesis of preeclampsia. Thus, evaluation of angiogenesis agonist and antagonist factors is of greater importance to understand the mechanisms responsible for this disorder.
Poster Presentations / Pregnancy Hypertension 1, Supplement 1 (2010) S43–S76
Aims: To evaluate whether circulating angiogenic and anti-angiogenic factors may differentiate early-onset from late-onset preeclampsia. Methods: The study was conducted in 86 women with preeclampsia diagnosed in the third trimester of pregnancy. Preeclampsia was classified according to the onset of clinical manifestation in early-onset (before 34 weeks of gestation; n=31) or in late-onset (from 34 weeks of gestation on; n=55) preeclampsia. Serum was obtained from the patients in the moment of the diagnosis and assayed for placental growth factor (PlGF), vascular endothelial growth factor (VEGF), Endostatin, soluble Endoglin (sEng) and soluble form of vascular endothelial growth factor receptor (sVEGFR-1) determination by enzyme-linked immunosorbent assay. Results: Early-onset preeclampsia was characterized by significant lower levels of PlGF (median 38.3 vs 123.5 pg/mL) and VEGF (median 23.1 vs 35.3 pg/mL) in serum as well as by higher serum levels of Endostatin (median 33.9 vs 22.6 ng/mL), sEng (median 54.7 vs 42.1 pg/mL) and sVEGFR-1 (median 5211.0 vs 4657.6 pg/mL) compared with late-onset preeclampsia. Conclusions: In this study serum levels of angiogenic and antiangiogenic factors prove useful in differentiating early-onset from lateonset preeclampsia in the third trimester of pregnancy. Therefore, these findings suggest that angiogenic factors determination may indicate that early- and late-onset preeclampsia have different pathophysiology.
P77 Maternal ophthalmic artery Doppler velocimetry in pregnancies complicated by hypertension disorders Jose Paulo Silva Netto 1 , Marta Alves Freitas 1 , Claudia Garcia Magalhaes 2 , Jose Carlos Peracoli 2 . 1 Gama Regional Hospital - Brasilia, Brazil; 2 Botucatu Medical School - Sao Paulo State University, Botucatu - Sao Paulo, Brazil Background: The ophthalmic artery Doppler is a non-invasive and objective method which permits to identify different forms and extent of this vessel involvement. Aims: To differentiate women with preeclampsia from those with chronic arterial hypertension through ophthalmic artery Doppler. Methods: Cross-sectional study analyzing 30 pregnant women with chronic arterial hypertension and 31 with preeclampsia. Doppler velocimetry of the ophthalmic artery evaluated the following parameters for quantifying the flow velocity waveforms: resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), peak diastolic velocity (PDV), end diastolic velocity (EDV) as well as the ratio between the velocity peaks (PR). Results: The average of the Doppler indices on pregnant women with preeclampsia and chronic hypertension were respectively: RI = 0.649± 0.067; 0.718±0.077, PI = 1.205±0.326; 1.555±0.373, PSV: 34.280±9.306; 35.206±9.941, PDV = 26.513±10.060; 19.752±5.847, EDV = 1.951±4.060; 9.696±3.223 and PR = 0.77±0.16; 0.57±0.11. The resistance and pulsatility indices of the ophthalmic artery Doppler on women with preeclampsia were significantly lower than those with chronic hypertension. The ratio of the velocity peak was significantly higher on preeclamptic women. The morphology of the Doppler waveforms differentiated pregnant women with chronic hypertension from those with preeclampsia. In women with chronic hypertension the first waveforms had a typical dichrotic standard with a proto notch and mesodiastolic notch followed by discreet velocity elevations. In pregnant women with preeclampsia significative changes were detected on flow velocity waveforms, with marked elevation on the second mesodiastolic velocity peak after the protodiastolic notch. Conclusion: The ophthalmic artery Doppler examination can be used for the differential diagnosis and for hypertensive syndromes classification along pregnancy, by waveforms morphology and quantitative indices differences.
P78 Behavior of ophthalmic artery in the early postpartum of women with severe preeclampsia Marta Alves Freitas 1 , Jose Paulo Silva Netto 1 , Vera Therezinha Borges 2 , Marcos Consonni 2 , José Carlos Peracoli 2 . 1 Gama Regional Hospital Brasilia, DF, Brazil; 2 Botucatu Medical School - Sao Paulo State University, Botucatu, Sao Paulo, Brazil Background: Preeclampsia is characterized by vascular compromise of the whole maternal body, including ophthalmic artery vasoconstriction. Aims: Considering that the clinical signs and symptoms of preeclampsia disappear spontaneously after pregnancy resolution, the present study aims at identifying whether the behavior of the parameters of ophthalmic Doppler artery change in the early postpartum in women with severe preeclampsia.
S63
Methods: Fifty women with severe preeclampsia underwent the Doppler examination of ophthalmic artery at two different times: twenty-four hours before the interruption of pregnancy and 48 hours after the pregnancy resolution. A Toshiba equipment with Nemio 17 linear 10MHz transducer evaluated the following parameters: resistance index (RI), pulsatility index (PI), systolic velocity peak (SVP), diastolic velocity peak (DVP), end diastolic velocity peak (EDVP) and ratio peak (RP). Wilcoxon and Mann-Witney tests were employed for statistical analysis with significant values set at p<0.05. Results: RI (0.67±0.08 × 0.74±0.07) and PI (1.29±0.35 × 1.69±0,67) were significantly higher after pregnancy resolution, while SVP (34.59 ±9.45 × 30.82±7.44), DVP (23.75±8.65 × 20.66±6.49) and EDVP (11.42± 4.20 ×8.36 ±4,75) were significantly lower after it. There was no significant difference between the RP measured before and after the pregnancy resolution. Conclusion: Significant changes on the ophthalmic artery Doppler velocimetry indices in women with severe preeclampsia showed significant different values when comparing pregnant and postpartum period, indicating early vascular recovery after the pregnancy resolution.
P79 Prototype automated immunoassays for sVEGF R1 and PlGF distinguish preterm preeclamptic from hypertensive or normotensive pregnancies: a prospective clinical study John R. Barton 1 , Shiraz Sunderji 2 , Beth Martin 2 , Patricia Nunnelly 3 , Kristin Jones 3 , Linda Rogers 3 , Cheryl Hodges-Savola 3 , Adele Golden 3 , Mary Strand 4 , Lori Frane-Lake 4 , Donald Wothe 4 . 1 Central Baptist Hospital, KY, USA; 2 The Toledo Hospital, USA; 3 Beckman Coulter, Inc., USA; 4 Abbott Northwestern Hospital, USA Objective: The goals of this study were to determine if automated immunoassays for soluble vascular endothelial growth factor type 1 (sVEGF R1) and placental growth factor (PlGF) correlate with the clinical diagnosis of preterm preeclampsia (PE) and if they distinguish hypertensive (HTN) disorders of pregnancy. Study design: Blood was collected at 20 to 36 weeks from 454 subjects enrolled in a prospective clinical study. In women with PE, samples were obtained at time of clinical diagnosis. Plasma concentrations of sVEGF R1 and PlGF were measured using prototype assays* for the family of Access® Immunoassay Systems from Beckman Coulter. Diagnostic cutoff values were determined by receiver operating characteristics (ROC) analyses. Results: Results are summarized in the table. Median sVEGF R1 concentrations were significantly higher (p<0.0001) and median PlGF concentrations were significantly lower (p<0.0001) in women with PE compared to women without PE. ROC analysis showed areas under the curve of 0.98 for both sVEGF R1 and PlGF. A cutoff of 14,000 pg/mL for sVEGF R1 provided a clinical sensitivity of 0.96 and specificity of 0.96. A cutoff of 94 pg/mL for PlGF provided a clinical sensitivity of 0.96 and specificity of 0.95. Table 1 Diagnosis Normotensive Chronic HTN only Preeclampsia Chronic HTN + PE
N
Median sVEGF R1 pg/mL (95% CI)
Median PlGF pg/mL (95% CI)
388 18 39 9
2416 (1992, 2632) 2277 (1254, 3662) 91,514 (64,118, 125,723) 59,533 (26,417, 85,559)
447 (396, 520) 364 (197, 587) 12.1 (8.3, 19.6) 18.9 (12.1, 42.1)
Conclusion: Access® prototype assays for sVEGF R1 and PlGF demonstrated high sensitivity and specificity for the clinical diagnosis of preterm preeclampsia. These assays clearly separated subjects with preeclampsia from normotensive and hypertensive subjects who did not develop preeclampsia. *Assays are under development and not available for clinical use.
P80 The imbalance between angiogenic and anti-angiogenic factors in preeclampsia – preliminary data Leandro De Oliveira 1 , Nelson Sass 1 , Antonio Fernandes Moron 1 , Ilda Kunii 1 , José Carlos Peraçoli 2 , Maria Peraçoli 2 , Niels Olsen Câmara 3 , Ananth Karumanchi 4 . 1 Federal University of São Paulo, Brazil; 2 Botucatu Medical School - UNESP, Brazil; 3 São Paulo University, USA; 4 Beth Israel Deaconess Medical Center and Harvard Medical School, Brazil Background: Recent reports have shown that an imbalance between proangiogenic (VEGF and PlGF) and anti-angiogenic factors (soluble fms-like
Poster Presentations / Pregnancy Hypertension 1, Supplement 1 (2010) S43–S76
(25-75 percentile): 76.5 (70.3-82.9) % and 59.0 (51.7-64.4) %, respectively). Furthermore, CD4+ helper and CD8+ cytotoxic T cells showed a similar pattern of intracellular galectin-1 expression in normal pregnancy. However, the proportion of galectin-1-expressing peripheral blood T (both helper and cytotoxic) and NK cells was markedly decreased in preeclampsia (for T cells: 30.6 (21.3-34.4) %, p<0.001; for NK cells: 42.9 (32.0-61.9) %, p<0.001). Conclusions: The majority of circulating NK and – to a lesser extent – T (helper and cytotoxic) cells shows intracellular galectin-1 expression in normal pregnancy. In preeclampsia, the proportion of galectin-1-positive T (both helper and cytotoxic) and NK cells in the peripheral blood is markedly decreased, which might contribute to the development of the generalized intravascular inflammatory reaction characteristic of the maternal syndrome of the disease.
P73 Structure and function of posterior cerebral arteries in a preeclampsia rat model Marjon Wiegman 1 , Anne Marijn van der Graaf 1 , Gerda Zeeman 1 , Jan Aarnoudse 1 , Rob Henning 2 , Hendrik Buikema 2 , Marijke Faas 3 . 1 Department of Obstetrics & Gynecology, University Medical Center Groningen, The Netherlands; 2 Department of Clinical Pharmacology, University Medical Center Groningen, The Netherlands; 3 Department of Medical Biology and Pathology, University Medical Center Groningen, The Netherlands Background: Eclampsia is thought to be a form of the posterior reversible encephalopathy syndrome, in which an acute rise in blood pressure causes breakthrough of autoregulation, hyperperfusion, blood-brain barrier disruption and cerebral edema formation. Because of the central role of the cerebrovasculature in the pathophysiology of eclampsia, this study assesses the effect of preeclampsia on myogenic activity and remodeling of cerebral arteries in the endotoxin-induced preeclampsia rat model. Methods: Nonpregnant (NP) and late-pregnant (LP; day 20) Wistar rats were infused with either saline (NP-Saline, n=9; LP-Saline, n=9) or 1.0 ug/kg body weight endotoxin (NP-endotoxin, n=7; LP-endotoxin, n=10) on day 14 of pregnancy or 6 days before sacrifice in NP animals. Third-order branches of the posterior cerebral artery from these animals were mounted in an arteriograph chamber to measure myogenic tone at intravascular pressures from 50-175 mmHg. Pressure of forced dilatation was determined using repeated-measures ANOVA. Passive measurements, i.e. passive diameter, wall thickness, and wall-to-lumen ratio, were obtained by adding papaverine. Two-way ANOVA with Bonferroni post-test was used to determine the effect of pregnancy and endotoxin on myogenic tone and passive measurements. Results: LP-endotoxin animals underwent forced dilatation at a lower pressure compared to the other three groups, i.e. between 125-150 mmHg for LP-endotoxin compared to 150-175 mmHg in the other groups. Also, LPendotoxin animals showed diminished myogenic tone at 175 mmHg versus NP-endotoxin (18.0±4.6 vs. 39.5±4.8%; p<0.05). No other differences in myogenic tone were found between the groups. Passive measurements were similar for all groups. Conclusion: These results suggest that no protective remodeling occurred in response to experimental mild preeclampsia. However, in LP-endotoxin animals pressure of forced dilatation was decreased compared to the other groups. This suggests that mild preeclampsia, but not uncomplicated pregnancy, may predispose the brain to autoregulatory breakthrough and development of eclampsia when blood pressure is elevated.
exposed only to systemic factors (n= 14). Controls were age-matched (0.80.9 gestation) Control Gravid (C-G; n=10) and Control Non-gravid (C-NG; n= 13; Follicular and Luteal) animals. UBF, SS, UA structure and function were measured. SS = 4 UBF * Viscosity/πr 3 ; viscosity @ shear rates > 60/sec. Impedance was measured using simultaneous UBF and perfusion pressure @ 120Hz. Asymmetric IUGR was observed with uterine space restriction. UBF and SS were greater in UP-G & C-G associated with higher oxygen delivery/extraction. UA endothelial eNOS and NO was elevated 2-4 fold in UP-G & C-G vs. UP-NG & C-NG. We observed normal vascular remodeling with gestation; vascular impedance metrics, structure, circumferential and longitudinal mechanical properties of UAs: UP-NG = C-NG and from UP-G = C-G. Furthermore, UP-NG UBF and SS were similar to Follicular-C-NG sheep and were greater then Luteal-C-NG. Isolating the non-gravid horn vasculature from SS rises and placental factors throughout gestation fully abrogated functional mechanical and structural remodeling of UAs: i.e. Diameter, Circumferential and Longitudinal Green Strain and Cauchy Stress, as well as Circumferential Incremental Elastic Modulus. Thus local, not systemic, placental factors during gestation are responsible for elevations in UA SS and remodeling. Formation of low resistance, uteroplacental vascular beds during pregnancy are a key element to inducing UA remodeling through elevated flow, eNOS and SS. NIH HL49210, HD38843, HL87144.
P75 Visual field defects after eclampsia Marjon Wiegman 1 , Anne Marijn van der Graaf 1 , Nina Roos 1 , Nomdo Jansonius 2 , Jan Aarnoudse 1 , Gerda Zeeman 1 . 1 Department of Obstetrics & Gynaecology, University Medical Center Groningen, The Netherlands; 2 Department of Ophthalmology, University Medical Center Groningen, The Netherlands Background: Eclampsia is thought to be a form of posterior reversible encephalopathy syndrome (PRES) in which cerebral edema formation leads to neurological symptoms, such as visual disturbances. During the acute phase of PRES, the most common visual abnormality is transient cortical blindness but homonymous anopia, visual neglect, and blurred vision can also occur. The reversibility of PRES has been questioned. In previous studies, eclamptic women showed persistent cerebral white matter lesions on MRI on both short and long term follow-up. In general, eclamptic patients regain their vision. However, incidentally visual field loss has been described to persist years after the acute phase and is thought to be related to persistent lesions or infarctions in the visual cortex. It is possible that unconscious homonymous anopia is present in formerly eclamptic patients, which is the subject of the current study. Methods: To assess the presence of visual field defects, 36 formerly eclamptic women, who experienced eclampsia between 1988 and 2008 underwent standard automatic perimetry using a Humphrey Field Analyzer with a 52-point grid covering the central field with a radius of 24 degrees and a threshold-related supra-threshold testing strategy. In case of repeated abnormal visual field testing the participant was referred for a formal full ophthalmologic examination to rule out other pathology. Results: Mean age and elapsed time (± standard deviation) since eclampsia was 40.8±7.4 and 10.7±5.3 years, respectively. Long term MRI follow up was available for 24 participants, of which 11 demonstrated cerebral white matter lesions. None of the 36 formerly eclamptic women demonstrated visual field loss. Conclusion: Although a substantial part of formerly eclamptic patients showed persistent cerebral lesions on MRI-scans, these lesions do not seem to induce visual field defects in this cohort. However, a larger group needs to be tested to definitely confirm these results.
P74 Local uteroplacental factors increase uterine blood flow (UBF) and shear stress (SS) in association with structural and mechanical indices, vascular impedance metrics, and eNOS/NO levels 1
1
1
1
Ronald Magness , Benjamin Sprague , Daniel Henao , Jayanth Ramadoss , Jill Koch 1 , Naomi Chesler 2 . 1 University of Wisconsin-Madison, USA; 2 University of Wisconsin, USA Vascular remodeling facilitates rises in UBF needed for fetal growth. Remodeling of the uterine vasculature normalize SS. Anatomically space-restricted uterine cavities are associated with preeclampsia/IUGR. We developed an ovine surgical model to create a unicornuate/didelphic uterus to study space restriction and uterine artery (UA) adaptations. Prior to conception (>60d), inter-corneal connections were severed, one horn was ligated leaving the ipsilateral gravid horn (UP-G) vasculature locally exposed to SS and uteroplacental factors and the contralateral non-gravid (UP-NG) horn vasculature
P76 Angiogenic and anti-angiogenic factors determination in early-onset and late-onset preeclampsia Maria Terezinha Peracoli 1 , Vera Therezinha Borges 2 , Camila Ferreira Bannwart 1 , Leonardo Teixeira Medeiros 1 , Ingrid Cristina Weel 1 , Mariana Romao 1 , Erika Nakaira-Takahagi 1 , José Carlos Peracoli 2 . 1 Institute of Biosciences/Sao Paulo State University, Botucatu, Sao Paulo, Brazil; 2 Botucatu Medical School/Sao Paulo State University, Botucatu, Sao Paulo, Brazil Background: Changes in circulating angiogenic factors have been implicated in the pathogenesis of preeclampsia. Thus, evaluation of angiogenesis agonist and antagonist factors is of greater importance to understand the mechanisms responsible for this disorder.
Poster Presentations / Pregnancy Hypertension 1, Supplement 1 (2010) S43–S76
Aims: To evaluate whether circulating angiogenic and anti-angiogenic factors may differentiate early-onset from late-onset preeclampsia. Methods: The study was conducted in 86 women with preeclampsia diagnosed in the third trimester of pregnancy. Preeclampsia was classified according to the onset of clinical manifestation in early-onset (before 34 weeks of gestation; n=31) or in late-onset (from 34 weeks of gestation on; n=55) preeclampsia. Serum was obtained from the patients in the moment of the diagnosis and assayed for placental growth factor (PlGF), vascular endothelial growth factor (VEGF), Endostatin, soluble Endoglin (sEng) and soluble form of vascular endothelial growth factor receptor (sVEGFR-1) determination by enzyme-linked immunosorbent assay. Results: Early-onset preeclampsia was characterized by significant lower levels of PlGF (median 38.3 vs 123.5 pg/mL) and VEGF (median 23.1 vs 35.3 pg/mL) in serum as well as by higher serum levels of Endostatin (median 33.9 vs 22.6 ng/mL), sEng (median 54.7 vs 42.1 pg/mL) and sVEGFR-1 (median 5211.0 vs 4657.6 pg/mL) compared with late-onset preeclampsia. Conclusions: In this study serum levels of angiogenic and antiangiogenic factors prove useful in differentiating early-onset from lateonset preeclampsia in the third trimester of pregnancy. Therefore, these findings suggest that angiogenic factors determination may indicate that early- and late-onset preeclampsia have different pathophysiology.
P77 Maternal ophthalmic artery Doppler velocimetry in pregnancies complicated by hypertension disorders Jose Paulo Silva Netto 1 , Marta Alves Freitas 1 , Claudia Garcia Magalhaes 2 , Jose Carlos Peracoli 2 . 1 Gama Regional Hospital - Brasilia, Brazil; 2 Botucatu Medical School - Sao Paulo State University, Botucatu - Sao Paulo, Brazil Background: The ophthalmic artery Doppler is a non-invasive and objective method which permits to identify different forms and extent of this vessel involvement. Aims: To differentiate women with preeclampsia from those with chronic arterial hypertension through ophthalmic artery Doppler. Methods: Cross-sectional study analyzing 30 pregnant women with chronic arterial hypertension and 31 with preeclampsia. Doppler velocimetry of the ophthalmic artery evaluated the following parameters for quantifying the flow velocity waveforms: resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), peak diastolic velocity (PDV), end diastolic velocity (EDV) as well as the ratio between the velocity peaks (PR). Results: The average of the Doppler indices on pregnant women with preeclampsia and chronic hypertension were respectively: RI = 0.649± 0.067; 0.718±0.077, PI = 1.205±0.326; 1.555±0.373, PSV: 34.280±9.306; 35.206±9.941, PDV = 26.513±10.060; 19.752±5.847, EDV = 1.951±4.060; 9.696±3.223 and PR = 0.77±0.16; 0.57±0.11. The resistance and pulsatility indices of the ophthalmic artery Doppler on women with preeclampsia were significantly lower than those with chronic hypertension. The ratio of the velocity peak was significantly higher on preeclamptic women. The morphology of the Doppler waveforms differentiated pregnant women with chronic hypertension from those with preeclampsia. In women with chronic hypertension the first waveforms had a typical dichrotic standard with a proto notch and mesodiastolic notch followed by discreet velocity elevations. In pregnant women with preeclampsia significative changes were detected on flow velocity waveforms, with marked elevation on the second mesodiastolic velocity peak after the protodiastolic notch. Conclusion: The ophthalmic artery Doppler examination can be used for the differential diagnosis and for hypertensive syndromes classification along pregnancy, by waveforms morphology and quantitative indices differences.
P78 Behavior of ophthalmic artery in the early postpartum of women with severe preeclampsia Marta Alves Freitas 1 , Jose Paulo Silva Netto 1 , Vera Therezinha Borges 2 , Marcos Consonni 2 , José Carlos Peracoli 2 . 1 Gama Regional Hospital Brasilia, DF, Brazil; 2 Botucatu Medical School - Sao Paulo State University, Botucatu, Sao Paulo, Brazil Background: Preeclampsia is characterized by vascular compromise of the whole maternal body, including ophthalmic artery vasoconstriction. Aims: Considering that the clinical signs and symptoms of preeclampsia disappear spontaneously after pregnancy resolution, the present study aims at identifying whether the behavior of the parameters of ophthalmic Doppler artery change in the early postpartum in women with severe preeclampsia.
S63
Methods: Fifty women with severe preeclampsia underwent the Doppler examination of ophthalmic artery at two different times: twenty-four hours before the interruption of pregnancy and 48 hours after the pregnancy resolution. A Toshiba equipment with Nemio 17 linear 10MHz transducer evaluated the following parameters: resistance index (RI), pulsatility index (PI), systolic velocity peak (SVP), diastolic velocity peak (DVP), end diastolic velocity peak (EDVP) and ratio peak (RP). Wilcoxon and Mann-Witney tests were employed for statistical analysis with significant values set at p<0.05. Results: RI (0.67±0.08 × 0.74±0.07) and PI (1.29±0.35 × 1.69±0,67) were significantly higher after pregnancy resolution, while SVP (34.59 ±9.45 × 30.82±7.44), DVP (23.75±8.65 × 20.66±6.49) and EDVP (11.42± 4.20 ×8.36 ±4,75) were significantly lower after it. There was no significant difference between the RP measured before and after the pregnancy resolution. Conclusion: Significant changes on the ophthalmic artery Doppler velocimetry indices in women with severe preeclampsia showed significant different values when comparing pregnant and postpartum period, indicating early vascular recovery after the pregnancy resolution.
P79 Prototype automated immunoassays for sVEGF R1 and PlGF distinguish preterm preeclamptic from hypertensive or normotensive pregnancies: a prospective clinical study John R. Barton 1 , Shiraz Sunderji 2 , Beth Martin 2 , Patricia Nunnelly 3 , Kristin Jones 3 , Linda Rogers 3 , Cheryl Hodges-Savola 3 , Adele Golden 3 , Mary Strand 4 , Lori Frane-Lake 4 , Donald Wothe 4 . 1 Central Baptist Hospital, KY, USA; 2 The Toledo Hospital, USA; 3 Beckman Coulter, Inc., USA; 4 Abbott Northwestern Hospital, USA Objective: The goals of this study were to determine if automated immunoassays for soluble vascular endothelial growth factor type 1 (sVEGF R1) and placental growth factor (PlGF) correlate with the clinical diagnosis of preterm preeclampsia (PE) and if they distinguish hypertensive (HTN) disorders of pregnancy. Study design: Blood was collected at 20 to 36 weeks from 454 subjects enrolled in a prospective clinical study. In women with PE, samples were obtained at time of clinical diagnosis. Plasma concentrations of sVEGF R1 and PlGF were measured using prototype assays* for the family of Access® Immunoassay Systems from Beckman Coulter. Diagnostic cutoff values were determined by receiver operating characteristics (ROC) analyses. Results: Results are summarized in the table. Median sVEGF R1 concentrations were significantly higher (p<0.0001) and median PlGF concentrations were significantly lower (p<0.0001) in women with PE compared to women without PE. ROC analysis showed areas under the curve of 0.98 for both sVEGF R1 and PlGF. A cutoff of 14,000 pg/mL for sVEGF R1 provided a clinical sensitivity of 0.96 and specificity of 0.96. A cutoff of 94 pg/mL for PlGF provided a clinical sensitivity of 0.96 and specificity of 0.95. Table 1 Diagnosis Normotensive Chronic HTN only Preeclampsia Chronic HTN + PE
N
Median sVEGF R1 pg/mL (95% CI)
Median PlGF pg/mL (95% CI)
388 18 39 9
2416 (1992, 2632) 2277 (1254, 3662) 91,514 (64,118, 125,723) 59,533 (26,417, 85,559)
447 (396, 520) 364 (197, 587) 12.1 (8.3, 19.6) 18.9 (12.1, 42.1)
Conclusion: Access® prototype assays for sVEGF R1 and PlGF demonstrated high sensitivity and specificity for the clinical diagnosis of preterm preeclampsia. These assays clearly separated subjects with preeclampsia from normotensive and hypertensive subjects who did not develop preeclampsia. *Assays are under development and not available for clinical use.
P80 The imbalance between angiogenic and anti-angiogenic factors in preeclampsia – preliminary data Leandro De Oliveira 1 , Nelson Sass 1 , Antonio Fernandes Moron 1 , Ilda Kunii 1 , José Carlos Peraçoli 2 , Maria Peraçoli 2 , Niels Olsen Câmara 3 , Ananth Karumanchi 4 . 1 Federal University of São Paulo, Brazil; 2 Botucatu Medical School - UNESP, Brazil; 3 São Paulo University, USA; 4 Beth Israel Deaconess Medical Center and Harvard Medical School, Brazil Background: Recent reports have shown that an imbalance between proangiogenic (VEGF and PlGF) and anti-angiogenic factors (soluble fms-like