Contribution of endogenous endothelin-1 to basal vascular tone during normal pregnancy and preeclampsia.

OBJECTIVE: The aim of this study was to determine the physiologic role for endogenous endothelin in the regulation of vascular tone during normal pregnancy and preeclampsia. The vascular sensitivity to endothelin-1 during pregnancy was studied also. STUDY DESIGN: Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of phosphoramidon, an endothelin-converting enzyme inhibitor, for 60 minutes, which was followed by co-infusion with endothelin-1 for 30 minutes. Three groups were studied: healthy nonpregnant women, normal pregnant women, and women with preeclampsia. RESULTS: There was a significant increase in forearm blood flow in the nonpregnant group after phosphoramidon infusion alone (73%+/-37%; P<.05). Phosphoramidon did not change forearm blood flow in pregnant subjects. Co-infusion with endothelin-1 significantly decreased forearm blood flow in both the nonpregnant and normal pregnant women (53%+/-7% and 40%+/-11%, respectively; P<.01). No response to endothelin-1 was found among women with preeclampsia. CONCLUSION: The vascular sensitivity to endothelin-1 is not altered during normal pregnancy in contrast to preeclamptic pregnancy, where no effect of endothelin-1 was seen. Reduced endothelin dependence during pregnancy might be one mechanism behind the fall in peripheral vascular resistance.

The role of endogenous endothelin in the regulation of uteroplacental and renal blood flow during pregnancy in conscious rats.

Advancing pregnancy is characterized by a ten-fold increase in uterine blood flow and a 50 per cent increase in renal blood flow. To evaluate the involvement of endogenous endothelin (ET) in these haemodynamic changes the effect of bosentan, an ETA/B receptor antagonist, on uteroplacental and renal blood flow was studied in awake pregnant Sprague-Dawley rats. Regional blood flows were measured using microsphere technique immediately prior to and 30 min after bosentan administration (20 mg/kg i.v.). Four groups of animals (term: 23 days) were included: bosentan was administered to ten rats at gestation day (GD) 19 and nine at GD 20-21. In addition, four rats at GD 19 and five animals at GD 20-21 received saline and served as control groups. Basal placental blood flow increased significantly from 19 days' gestation to 20-21 days. Basal myometrial blood flow did not change with gestational age. At gestation day 19 bosentan increased placental and myometrial blood flow significantly (80 per cent and 43 per cent, respectively, P<0.05). This effect was not observed at gestation days 20-21. Renal blood flow did not change in response to bosentan at GD 19 but decreased by 20 per cent at GD 20-21 (P<0.01). In conclusion, in the awake pregnant rat there is a significant endogenous ET dependent vasoconstrictor tone in the uteroplacental vessels that diminishes towards term. We speculate that this change in responsiveness to endogenous ET contribute to the increase in placental blood flow in late gestation.

Endothelial function in myometrial resistance arteries of normal pregnant women perfused with syncytiotrophoblast microvillous membranes.

OBJECTIVE: To investigate the effects of syncytiotrophoblast microvillous membranes (STBM) in concentrations, found in vivo in women with pre-eclampsia, on endothelial function in isolated resistance arteries. SETTING: Department of Obstetrics and Gynaecology, Huddinge University Hospital, Stockholm. SAMPLE: Twenty-nine myometrial resistance arteries isolated from biopsies of healthy term pregnant women, obtained during caesarean section. METHODS: The myometrial arteries were mounted in a pressure arteriograph and perfused intraluminally for three hours with STBM (20 to 2000ng/mL) or with erythrocyte membranes or physiological salt solution as controls, all substituted with 0.5% bovine serum albumin. Bradykinin concentration-response curves were performed before and after perfusion. MAIN OUTCOME MEASURES: The bradykinin concentrationresponse curves were fitted to the Hill equation and maximal dilation and the pEC50 values were determined from these fits. Differences within groups were analysed with a paired Student's t test. Electron microscopic evaluation of the endothelium was performed. RESULTS: Neither STBM nor erythrocyte membrane perfusion affected maximal dilation or the pEC50 values of the bradykinin concentration-response curves at any concentration. Examination by electron microscopy showed no obvious damage to the endothelium after perfusion with STBM or erythrocyte membranes. CONCLUSION: Perfusion with STBM in concentrations up to 100 times those reported in pre-eclampsia has no significant effect on bradykinin-mediated dilation in isolated myometrial arteries.

Altered mRNA expression of ecNOS and iNOS in myometrium and placenta from women with preeclampsia.

OBJECTIVE: Preeclampsia is a syndrome involving dysfunction of vascular endothelium and imbalance between endothelium derived constricting and relaxing factors. Recent evidence suggests that endothelium-derived nitric oxide (NO) plays a role in the regulation of vascular resistance during normal pregnancy and preeclampsia. NO is a potent vasodilator and is generated by the catalytic action of nitric oxide synthases ecNOS and iNOS in myometrium and placenta. METHODS: In this study mRNA expressions of ecNOS and iNOS were compared in myometrium and placenta. Biopsies were collected from women with preeclampsia (n=8) and normal pregnancies (n=12). ecNOS and iNOS mRNA levels were determined using RT-PCR and expressed as arbitrary units after correction for control GAPDH gene mRNA levels. RESULTS: The mRNA expression of ecNOS was significantly higher in both myometrium (p<0.05) and placenta (p<0.05) from women with preeclampsia compared to that in normal pregnancies, while the iNOS mRNA level was not altered in myometrium and lower in placenta (p<0.05) from women with preeclampsia. CONCLUSIONS: The higher ecNOS mRNA expression might be a compensatory response to an impaired vasodilatation in the uteroplacental circulation during preeclampsia. Whether the similar and reduced levels of iNOS mRNA expression in myometrium and placenta, respectively, in women with preeclampsia is of importance remains to be further evaluated.

Changes in flow velocity, resistance indices, and cerebral perfusion pressure in the maternal middle cerebral artery distribution during normal pregnancy.

BACKGROUND: There are few longitudinal data currently available detailing the normal changes in maternal cerebral hemodynamics during human pregnancy. This lack of information limits the study of pregnancy-associated cerebrovascular adjustments and, in particular, preeclampsia, where the brain appears to be especially susceptible to ischemic and encephalopathic injury. Our objective was to define the hemodynamic changes, specifically velocity, resistance indices, and cerebral perfusion pressure, in the middle cerebral artery (MCA) distribution of the brain during normal pregnancy. METHODS AND MATERIALS: Transcranial Doppler ultrasound was used to determine the systolic, diastolic and mean blood velocities in the middle cerebral arteries in non-laboring women studied longitudinally during normal gestation. The resistance index (RI), pulsatility index (PI), and cerebral perfusion pressure (CPP) were calculated using the velocity and blood pressure data. Data were analyzed using a longitudinal statistical model incorporating random patient effects and a homoscedastic (compound symmetric) variance-covariance structure over time (gestational age). The predicted mean value (Least Squares Mean), and the 5th and 95th percentiles, were defined for normal pregnancy. RESULTS: MCA systolic velocity decreased (24%) as did the mean velocity (17%). The diastolic velocity did not change significantly. The MCA RI decreased by 19% and the PI decreased by 25%. The MCA CPP increased by 52% between 12 and 40 weeks of gestation. CONCLUSIONS: The normative ranges for MCA velocity, RI, and CPP have been defined in normal human pregnancy using longitudinally collected data. By having a defined normal range, identification of abnormalities in cerebral hemodynamics during pregnancy is now possible, and this may help researchers and clinicians to elucidate etiologies and treatments for pregnancy-related pathophysiologic states such as preeclampsia

Pregnant women with chronic hypertension and superimposed pre-eclampsia have high cerebral perfusion pressure.

OBJECTIVE: To determine any differences in cerebral perfusion pressure in patients with chronic hypertension compared with those with chronic hypertension and superimposed pre-eclampsia. DESIGN: A prospective observational study. SETTING: University hospital clinic and labour and delivery suite. PARTICIPANTS: Fifteen women with chronic hypertension and 15 with superimposed pre-eclampsia. METHODS: Transcranial Doppler ultrasound was used to measure blood velocity in the middle cerebral arteries of the patients. Systemic blood pressure in the brachial artery was measured simultaneously. Middle cerebral artery. resistance index, pulsatility index, and cerebral perfusion pressure were calculated and plotted on the same axes as data from normal pregnant women. Cerebral perfusion pressure values outside of the 5th and 95th centiles were regarded as abnormal. Cerebral perfusion pressure data from the chronic hypertension and superimposed pre-eclampsia groups were also expressed in terms of the number of normative standard deviations from the mean value for normal pregnancy (Multiples of the Standard Deviation: MOS). All studies were conducted before labour, under similar conditions, and before volume expansion or treatment. Statistical analysis was by Student's t test and Fisher's exact test as appropriate with significance set at a two-tailed P<0.05. RESULTS: Patient demographics and blood pressure were not significantly different between the two groups. The resistance index and pulsatility index were not significantly different (neither absolute nor multiples of the standard deviation values). The absolute cerebral perfusion pressure was significantly higher in the patients with superimposed pre-eclampsia. The group of women with superimposed pre-eclampsia had a significantly higher mean value of cerebral perfusion pressure measured as multiples of the standard deviation from the mean value for normal pregnancy, despite there being no blood pressure difference. CONCLUSIONS: Superimposed pre-eclampsia is associated with significantly higher cerebral perfusion pressure measurements compared with women with uncomplicated chronic hypertension. This is not directly related to a higher blood pressure. The difference in cerebral perfusion pressure may be used to speculate upon the pathophysiology of the increased risk for eclampsia seen in patients with superimposed pre-eclampsia.

Altered gene expression of endothelin-A and endothelin-B receptors, but not endothelin-1, in myometrium and placenta from pregnancies complicated by preeclampsia.

OBJECTIVE: The aim of the present study was to compare the mRNA expression of endothelin-1 (ET-1), ET-1 receptors ET(A) and ET(B) in myometrium and placenta obtained from biopsies collected from women with preeclampsia (n=10) or normal pregnant (n=12). METHODS: The mRNA levels of ET-1 ET(A) and ET(B) were determined using RT-PCR and expressed as arbitrary units after correction for control GAPDH gene mRNA levels. RESULTS: The mRNA levels of ET-1 in myometrium and placenta were not altered in women with preeclampsia compared to normal pregnant. The mRNA expression of ET(A) was significantly reduced (p<0.05) in both placenta and myometrium from women with preeclampsia. The mRNA levels of ET(B) were similar in placentas from both preeclamptic and normal pregnant women, but higher in myometrium (p<0.05) from women with preeclampsia. CONCLUSIONS: These results indicate that the higher levels of ET-1 seen in preeclamptic women do not depend on an altered mRNA transcription of ET-1. The significantly reduced mRNA expression of ET(A) receptor in myometrium and placenta in women with preeclampsia might represent downregulation of the receptors due to the increased levels of ET-1 in uteroplacental circulation in this disorder. Much more research is needed before the role of ET(B) receptors in preeclampsia can be clarified.

Evaluation of a noninvasive transcranial Doppler and blood pressure-based method for the assessment of cerebral perfusion pressure in pregnant women.

OBJECTIVE: We have developed a Doppler method for the estimation of cerebral perfusion pressure (CPP) using noninvasive techniques. Our objective was to evaluate our new method in pregnant women. METHODS AND MATERIALS: Laboring women with a lumbar epidural in situ had transcranial Doppler interrogation of the maternal middle cerebral artery (MCA) to measure systolic, diastolic, and mean velocities. A pressure transducer was connected to the epidural catheter and pressure was recorded. Systolic (SBP), diastolic (DBP), and mean (MAP) blood pressure were taken with a Dinamap monitor. Doppler estimated CPP (mm Hg) = [V(mean)/(V(mean) - V(diastolic)](MAP - DBP) and directly measured CPP = MAP - Epidural pressure data were plotted on a Bland-Altman graph with limits of agreement. The mean difference (the mean of the sum of both positive and negative differences) and absolute difference (the mean of the sum of the absolute differences) were calculated. In addition, linear and polynomial regression analyses were performed. RESULTS: Twenty laboring women were studied. All had normal pregnancies. The mean maternal age was 28 +/- 7 years and the mean gestational age was 39 +/- 2 weeks. The mean maternal MAP was 77 +/- 12 mm Hg. The Bland-Altman plot showed a mean difference of 2.2 mm Hg at a mean CPP of 65 +/- 12 mm Hg; with a standard deviation of 4.8 mm Hg, the absolute difference was 3.9 +/- 3.0 mm Hg at a mean CPP of 65 +/- 12 mm Hg. The regression analysis showed an r = 0.92, r(2) = 0.86, and p < 0.0001. CONCLUSIONS: Our formula allows the estimation of CPP using a simple calculation and noninvasively acquired data. This method may be of use for frequent, easy, and accurate CPP and intracranial pressure estimation and may, as such, have significant research and clinical applications.

Preeclampsia: evidence for impaired shear stress-mediated nitric oxide release in uterine circulation.

OBJECTIVE: We sought to compare flow-mediated dilatation and myogenic and norepinephrine-induced tone in myometrial resistance arteries from women with preeclampsia and healthy pregnant women and to evaluate the role that nitric oxide may play in these responses. STUDY DESIGN: Arteries (approximately 200 microm, at 50 mm Hg) were dissected from myometrial biopsy specimens from women undergoing emergency cesarean delivery because of preeclampsia (n = 6) and from healthy control subjects undergoing planned cesarean delivery (n = 9). Responses to intraluminal flow, pressure, and a constrictor agonist (norepinephrine, 10(-6) mol/L) were studied in the absence and presence of the nitric oxide synthase inhibitor N omeganitro-L -arginine (10(-4) mol/L). Myogenic and norepinephrine-induced tone were calculated after the determination of artery diameter in the absence of extracellular calcium and in the presence of papaverine (10(-4) mol/L). RESULTS: An increase in intraluminal flow led to dilatation of isolated myometrial arteries from healthy gravid women, whereas flow-mediated dilatation was absent in arteries from gravid patients with preeclampsia (increase in diameter at maximum flow rate of 204 microL/min, 28% +/- 5% in healthy gravid patients vs -15% +/- 6% in gravid women with preeclampsia; analysis of variance, P <.05). Addition of N omega-nitro-L -arginine had no significant effect on flow-mediated responses in arteries from women with preeclampsia, whereas flow-mediated dilatation was abolished after addition of N omega-nitro-L -arginine in arteries from healthy gravid women (increase in diameter at a maximum flow rate of 204 microL/min, 28% +/- 5% control vs -9% +/- 5% N omega-nitro-L -arginine; analysis of variance, P <.05). Arteries from women with preeclampsia developed pressure-induced myogenic and norepinephrine-induced tone, similar to that obtained in arteries from healthy gravid women. In arteries from gravid women with preeclampsia, inhibition of nitric oxide synthase enhanced myogenic-induced tone (25% +/- 4% control vs 35% +/- 5% N omega-nitro-L -arginine; P <.05) and norepinephrine-induced tone (36% +/- 4% control vs 46% +/- 6% N omega-nitro-L -arginine; P <.05), as in arteries from healthy gravid women. CONCLUSIONS: Nitric oxide may participate in modulation of pressure- and norepinephrine-induced tone even in preeclampsia, but the shear stress-mediated release of nitric oxide is absent. Failure of shear stress-mediated dilation in myometrial arteries from gravid women with preeclampsia might contribute to the impaired uteroplacental blood flow in this disease.

Modulation of vascular tone by nitric oxide and endothelin 1 in myometrial resistance arteries from pregnant women at term.

OBJECTIVE: We evaluated the role of endothelium-derived nitric oxide and endothelin 1 in the modulation of myogenic tone, norepinephrine-induced tone, and flow-mediated responses in resistance arteries from pregnant women at term. STUDY DESIGN: Arteries (approximately 200 microm at 50 mm Hg; n = 27) were dissected from myometrial biopsies obtained from women undergoing elective cesarean delivery at term and mounted in a pressure arteriograph. Responses to intraluminal flow, pressure, and norepinephrine were studied in the absence and presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine and the endothelin-converting enzyme inhibitor phosphoramidon. RESULTS: Pressure-induced (80 mm Hg) myogenic tone was significantly enhanced after incubation with Nomega-nitro-L-arginine (33% +/- 8% vs 24% +/- 4%; P <.05), whereas phosphoramidon significantly reduced myogenic tone (24% +/- 5% vs 33% +/- 5%; P <.05). A combination of Nomega-nitro-L -arginine and phosphoramidon did not affect myogenic tone. Norepinephrine-induced tone was significantly enhanced after nitric oxide synthase inhibition (49% +/- 6% vs 41% +/- 5%; P <.05) but was not affected by phosphoramidon. Flow-mediated dilatation was increased in the presence of phosphoramidon compared with flow-induced dilatation in physiologic salt solution (maximum dilatation, 57% +/- 12% vs 30% +/- 5%; analysis of variance, P <.05), and all flow-induced dilatation was abolished by Nomega-nitro-L -arginine. CONCLUSIONS: Nitric oxide and endothelin 1 may play a significant role in modulation of myogenic tone and flow-mediated responses in the resistance vasculature of the uterine circulation in normal pregnancy.

Prediction of maternal and fetal complications in preeclampsia.

INTRODUCTION: Preeclampsia is associated with an increased risk for maternal and fetal morbidity. The aim of this study was to identify factors predicting for maternal or fetal complications. MATERIAL AND METHODS: One hundred and eleven patients with preeclampsia were included. Endpoint variables were maternal and fetal complications. Any of the diagnosis eclampsia, hemolysis elevated liver low platelet (HELLP) syndrome, oliguria or placental abruption was considered a maternal complication. Fetal complications were: small for gestational age (SGA) infant, umbilical artery pH<7.10 and admittance of the infant to a neonatal intensive care unit (NICU). Independent variables were maternal age, parity, gestational age, renal function, platelet count, liver enzymes and blood pressure. Logistic regression analysis was used for statistical evaluation. RESULTS: The following independent significant predictors were identified: Maternal complication (n=10) was predicted only by diastolic blood pressure; odds ratio (OR) 1.13 (95% confidence interval 1.01-1.25). SGA (n=21) was associated with maternal prepregnancy weight, OR 0.94 (0.89-0.99) and gestational age at debut of preeclampsia, OR 0.97 (0.94-0.99). NICU admittance (n=31) was only predicted by gestational age at delivery, OR 0.80 (0.67-0.96). No association was found between any of the independent variables and a low umbilical artery pH (n= 10). CONCLUSIONS: In the surveillance of patients with established preeclampsia, the value of serial blood and urine sampling, which is common practice in many obstetrical units, might be questioned.

Is carbohydrate metabolism altered among women who have undergone a preeclamptic pregnancy?

OBJECTIVE: To compare women after a preeclamptic pregnancy with women after a normal pregnancy with respect to androgenic-anabolic status and carbohydrate and lipid profiles. METHOD: Twenty-one patients and 22 controls were followed up to 26-119 weeks after delivery. Blood was sampled for analyses of insulin, glucose, insulin growth factor-1, lipids, androgens, sex hormone-binding globulin (SHBG) and uric acid. Anthropometric data and blood pressure were recorded. Data are presented as median and ranges (within parentheses) or mean +/- SEM where appropriate. Comparisons were made by unpaired t test or Mann-Whitney U test, respectively. RESULTS: Significantly higher values were found in the preeclampsia than in the control group for fasting insulin, fasting glucose, fasting insulin resistance index (FIRI, fasting glucose x fasting insulin/25), serum triglycerides, uric acid and blood pressure. There were no differences in androgen status and IGF-1 levels. CONCLUSION: Patients with a recent history of preeclampsia demonstrate signs of relative insulin resistance, hypertriglyceridemia and hyperuricemia as well as increased blood pressure as compared with women who had a normal pregnancy. However, in contrast to other women with insulin resistance, they have a normal androgen status.

Change in estimated cerebral perfusion pressure after treatment with nimodipine or magnesium sulfate in patients with preeclampsia.

OBJECTIVE: Data are accumulating to suggest that cerebral perfusion pressure may be either abnormally high or low in preeclampsia and eclampsia. Little is known of the cerebral perfusion pressure effects of magnesium sulfate or nimodipine. Our objective in this study was to compare the change in cerebral perfusion pressure in patients with severe preeclampsia randomly selected to receive nimodipine or magnesium sulfate. STUDY DESIGN: Patients with severe preeclampsia were randomly selected to receive magnesium sulfate (6 g bolus and 2 g/hr intravenous infusion) or nimodipine (60 mg taken orally every 4 hours). Transcranial Doppler ultrasonography was used to measure flow velocities in the right and left middle cerebral arteries, and the results were averaged. Measurements were obtained before treatment (baseline) and 30 minutes after the magnesium sulfate bolus was completely infused or 30 minutes after the nimodipine was ingested. Studies were performed before any other intervention. The person performing the ultrasonography was unaware of the patient's group assignment. Estimated cerebral perfusion pressure was calculated with the following formula: Estimated cerebral perfusion pressure = Velocity(mean) x [(Blood pressure(mean ) - Blood pressure(diastolic ))/(Velocity(mean) - Velocity(diastolic ))]. The difference between estimated cerebral perfusion pressure at baseline and after treatment was compared between the 2 groups by means of the Mann-Whitney rank sum test. RESULTS: Nine patients were randomly selected to receive nimodipine and 12 to receive magnesium sulfate. Patient demographics and severity of condition were not significantly different between the 2 groups. The change in estimated cerebral perfusion pressure was significantly different between the groups. Estimated cerebral perfusion pressure increased after nimodipine use and decreased after magnesium sulfate use. CONCLUSION: Shortly after administration to patients with severe preeclampsia, nimodipine resulted in increased cerebral perfusion pressure in comparison with magnesium sulfate.

Are women with polycystic ovary syndrome at an increased risk of pregnancy-induced hypertension and/or preeclampsia?

OBJECTIVE: To study whether there is an increased risk of glucose intolerance and hypertensive complications during pregnancy in women with polycystic ovary syndrome (PCOS) and if there is an adverse pregnancy outcome. METHODS: In a retrospective case-control study, pregnancies and neonatal outcome were compared in 33 women with PCOS and 66 women without PCOS. The women were treated at Huddinge University Hospital; antenatal care was given at associated outpatient units. MAIN OUTCOME MEASURES: Blood glucose and blood pressure during the different trimesters. Pregnancy outcome in terms of gestational length, birth weight, and need for neonatal intensive care. RESULTS: No significant differences were found in blood glucose levels between the groups. There were also no differences in blood pressure during the first and second trimester. However, during the third trimester and labor, the PCOS group had a significantly higher blood pressure than the control group. Apart from a tendency toward reduced growth of twins in PCOS mothers, the babies were healthy, overall, with few problems in the neonatal period. CONCLUSIONS: No major differences with regard to perinatal outcome in pregnant women with and without PCOS were found. An increased risk of hypertensive disorders in the third trimester and during labor was demonstrated in the PCOS group. This suggests that in the antenatal care of women with PCOS, attention should focus on blood pressure in order to reduce the risks of morbidity associated with hypertension.

Association of cerebral perfusion pressure with headache in women with pre-eclampsia.

OBJECTIVE: To study estimated cerebral perfusion pressure and its relation to headache and scotomata in women with pre-eclampsia. DESIGN: Prospective, observational study. SETTING: University teaching hospitals. POPULATION: Seventy-nine pre-eclamptic women with (n = 42) and without (n = 37) headache. Patients with scotomata were also studied separately. METHODS: Transcranial Doppler ultrasound was used to estimate the resistance index, pulsatility index, and estimated cerebral perfusion pressure in the middle cerebral artery. eCPP data were plotted on the same axes as the mean (and 5th and 95th% prediction limits) eCPP data from 63 normal pregnant women followed longitudinally through pregnancy. Data outside of the 95% prediction limits were regarded as abnormal. Data from the pre-eclamptic women were also expressed in terms of the number of standard deviations from the mean value established for normal pregnancy (multiples of the standard deviation: MOS). All studies were prior to labour, under similar conditions, and before volume expansion or treatment. Analysis of data was performed using Student's t test, Mann-Whitney U test, ANOVA, and Fisher's exact test with two-tailed P < 0.05, and receiver operating characteristic curve analysis with a one-tailed P < 0.05. MAIN OUTCOME MEASURES: Resistance index, pulsatility index, and eCPP. RESULTS: Pre-eclamptic women with headache were much more likely to have abnormal eCPP (34/42; 88%) than those without headache (18/37; 49%), P = 0.004, OR 4.5 (95% CI 1.5 to 13.9). There were no differences in terms of MOS in the resistance index or pulsatility index between the two groups, but estimated perfusion pressure, expressed as multiples of the standard deviation in the group with headache, was significantly higher than in the women without. Headache was noted in both over-perfusion and under-perfusion states. Only women with headache had scotomata, and their presence was not related to the severity of the headache or any difference in resistance indices or eCPP. CONCLUSIONS: Headache in women with pre-eclampsia is strongly associated with the presence of abnormal cerebral perfusion pressure. This information may be of use in clinical management.

Preeclampsia may cause both overperfusion and underperfusion of the brain: a cerebral perfusion based model.

BACKGROUND: The hypothesis was that low cerebral perfusion pressure is more common in women with mild preeclampsia as compared to those with severe preeclampsia, while high cerebral perfusion pressure is more common in women with severe preeclampsia than in women with mild preeclampsia. DESIGN: Prospective, observational study. SETTING: University teaching hospitals. METHODS: Transcranial Doppler ultrasound was used to measure the blood velocity in the middle cerebral arteries of 54 patients with mild preeclampsia and 44 patients with severe preeclampsia. Blood pressure was measured simultaneously. Cerebral perfusion pressure was calculated and plotted on the same axes as data from 63 normal pregnant women. Data outside of the 95% prediction limits were regarded as abnormal. All studies were prior to labor, and before volume expansion or treatment. ANALYSIS: Student's t-test, Mann Whitney U test, and Fisher's exact test as appropriate with two-tailed p<0.05. MAIN OUTCOME MEASURE: The number of patients in each group with cerebral perfusion pressure values outside the normal 95% prediction limits. RESULTS: Almost the same number of women with mild (21/54=39%) and severe (15/44=34%) preeclampsia had measurements within the normal range (p=0.78). Mild preeclamptic women were more likely to have low (28/54=52%) rather than high cerebral perfusion pressure (p<0.001), while severe preeclamptics were more likely to have high cerebral perfusion pressure (26/44=59%) than low (p<0.001). CONCLUSIONS: In preeclampsia the brain can be normally perfused, underperfused and over-perfused. Although many women with mild preeclampsia will have underperfusion (52%), and a significant number of women with severe preeclampsia will have overperfusion (59%), many preeclamptic women have cerebral perfusion within the normal range.

Effects of blood pressure on orbital and middle cerebral artery resistances in healthy pregnant women and women with preeclampsia.

OBJECTIVE: The object of the study was to test the hypothesis that preeclampsia leads to an abnormal vascular response to increasing blood pressure in cerebral vessels by analyzing the relationship between mean arterial pressure and resistance index in the central retinal, ophthalmic, and middle cerebral arteries in women with normal pregnancies and women with preeclampsia. STUDY DESIGN: Transcranial and color flow Doppler ultrasonographic studies were used to determine systolic, diastolic, and mean velocities and the resistance indexes in the central retinal, ophthalmic, and middle cerebral arteries in 24 women with normal pregnancies and 18 women with preeclampsia. In each group the relationship between the mean arterial pressure and the resistance index was determined for each artery by means of linear regression analysis. The Pearson correlation coefficients for each mean arterial pressure versus resistance index relationship were compared between the groups. In a separate analysis middle cerebral artery data obtained from 79 women with preeclampsia (with and without headache) were compared with data from the normal pregnancy group and analyzed in terms of the relationship between mean arterial pressure and resistance index. RESULTS: The resistance index in women with normal pregnancies decreased with increasing mean arterial pressure in all 3 vessels studied (ophthalmic artery r = -0.33, central retinal artery r = -0. 43, middle cerebral artery r = -0.30). In the women with preeclampsia, however, as mean arterial pressure increased the resistance index increased in the orbital vessels and decreased in the middle cerebral artery (ophthalmic artery r = 0.54, central retinal artery r = 0.65, middle cerebral artery r = -0.25). The correlation coefficients in the women with preeclampsia were significantly different from those in the women with normal pregnancies for the ophthalmic and central retinal arteries (P =. 001) but not for the middle cerebral artery (P =.8). Within-group analysis in the patients with normal pregnancies showed no differences between the correlation coefficients of the studied vessels. In the women with preeclampsia the ophthalmic artery (P =. 02) and the central retinal artery (P =.005) were significantly different from the middle cerebral artery but not from each other. Women with preeclampsia who had headache had a different correlation coefficient for the middle cerebral artery than did those without headache (r = -0.34 versus r = 0.23; P <.001). The correlation coefficient for the middle cerebral artery for women with preeclampsia without headache was not significantly different from the central retinal artery and ophthalmic artery correlation coefficients in the general preeclampsia group. CONCLUSIONS: Women with preeclampsia demonstrate a different relationship between blood pressure and resistance index in the ophthalmic and central retinal arteries than do women with normal pregnancies. In the middle cerebral artery, however, preeclampsia does not appear to affect the resistance index response to increasing mean arterial pressure in women with headache. In women with preeclampsia without headache the relationship seen in the ophthalmic artery and central retinal artery is preserved in the middle cerebral artery. This may indicate a failure in the autoregulatory capacity of the middle cerebral artery in the presence of headache. Alternatively, the resistance index response in the ophthalmic artery and central retinal artery may represent small-caliber vessel vasospasm that is not present in the middle cerebral artery in women with preeclampsia who have headache.