Experimental preeclampsia in rats affects vascular gene expression patterns.

Normal pregnancy requires adaptations of the maternal vasculature. During preeclampsia these adaptations are not well established, which may be related to maternal hypertension and proteinuria. The effects of preeclampsia on the maternal vasculature are not yet fully understood. We aimed to evaluate gene expression in aortas of pregnant rats with experimental preeclampsia using a genome wide microarray. Aortas were isolated from pregnant Wistar outbred rats with low-dose LPS-induced preeclampsia (ExpPE), healthy pregnant (Pr), non-pregnant and low-dose LPS-infused non-pregnant rats. Gene expression was measured by microarray and validated by real-time quantitative PCR. Gene Set Enrichment Analysis was performed to compare the groups. Functional analysis of the aorta was done by isotonic contraction measurements while stimulating aortic rings with potassium chloride. 526 genes were differentially expressed, and positive enrichment of "potassium channels", "striated muscle contraction", and "neuronal system" gene sets were found in ExpPE vs. Pr. The potassium chloride-induced contractile response of ExpPE aortic rings was significantly decreased compared to this response in Pr animals. Our data suggest that potassium channels, neuronal system and (striated) muscle contraction in the aorta may play a role in the pathophysiology of experimental preeclampsia. Whether these changes are also present in preeclamptic women needs further investigation.

Regional distribution of cerebral white matter lesions years after preeclampsia and eclampsia.

OBJECTIVE: To assess the distribution of cerebral white matter lesions in women who had eclampsia, preeclampsia, or normotensive pregnancies. The pathophysiology of these lesions, more often seen in formerly eclamptic and preeclamptic women, is unclear but may be related to a predisposition for vascular disease, the occurrence of the posterior reversible encephalopathy syndrome, or both while pregnant. Assessing the distribution of such lesions may give insight into their pathophysiology and possible consequences. METHODS: This retrospective cohort study determined the presence, severity, and location of white matter lesions on cerebral magnetic resonance imaging scans of 64 formerly eclamptic, 74 formerly preeclamptic, and 75 parous control women. RESULTS: Formerly preeclamptic and eclamptic women have white matter lesions more often (34.4% [n=47] compared with 21.3% [n=16]; P<.05) and more severely (0.07 compared with 0.02 mL; P<.05) than parous women in a control group. In all women, the majority of lesions was located in the frontal lobes followed by the parietal, insular, and temporal lobes. CONCLUSION: White matter lesions are more common in women with prior pregnancies complicated by preeclampsia or eclampsia compared with parous women in a control group. In no group does regional white matter lesion distribution correspond to the occipitoparietal edema distribution seen in posterior reversible encephalopathy syndrome.

Structure and function of cerebral and mesenteric resistance arteries in low-dose endotoxin-infused pregnant rats.

OBJECTIVE: Since the cerebrovasculature likely plays a prominent role in the pathophysiology of eclampsia, we assessed the effects of low-dose endotoxin-induced experimental preeclampsia on the function and structure of rat posterior cerebral arteries (PCA) and mesenteric arteries (MA). METHODS: Nonpregnant (NP) and pregnant (P) rats were infused with saline (NP-CTL, n=9; P-CTL, n=9) or low-dose endotoxin (NP-endotoxin, n=9; P-endotoxin, n=10). Myogenic activity, pressure of forced dilatation (FD) and structural properties were evaluated in PCA and MA. RESULTS: PCA underwent FD between 125 and 150mmHg in P-endotoxin (repeated measures ANOVA vs 75mmHg; P<0.05) and between 150 and 175mmHg in P-CTL and NP animals (repeated measures ANOVA vs 75mmHg; P<0.05). PCA myogenic tone was unaffected by pregnancy or endotoxin, however, pregnancy decreased the MA myogenic tone (P<0.05 vs NP). Passive characteristics of PCA and MA were unaffected by pregnancy or endotoxin. CONCLUSION: Low-dose endotoxin-infusion during pregnancy, but not pregnancy alone, decreased the pressure of FD in PCA. This may predispose to cerebral autoregulatory breakthrough and edema formation during increased blood pressure as seen in eclampsia.

Endothelium-dependent relaxation and angiotensin II sensitivity in experimental preeclampsia.

OBJECTIVE: We investigated endothelial dysfunction and the role of angiotensin (Ang)-II type I (AT1-R) and type II (AT2-R) receptor in the changes in the Ang-II sensitivity in experimental preeclampsia in the rat. METHODS: Aortic rings were isolated from low dose lipopolysaccharide (LPS) infused pregnant rats (experimental preeclampsia; n=9), saline-infused pregnant rats (n=8), and saline (n=8) and LPS (n=8) infused non-pregnant rats. Endothelium-dependent acetylcholine-mediated relaxation was studied in phenylephrine-preconstricted aortic rings in the presence of vehicle, N(G)-nitro-L-arginine methyl ester and/or indomethacin. To evaluate the role for AT1-R and AT2-R in Ang-II sensitivity, full concentration response curves were obtained for Ang-II in the presence of losartan or PD123319. mRNA expression of the AT1-R and AT2-R, eNOS and iNOS, COX1 and COX2 in aorta were evaluated using real-time RT-PCR. RESULTS: The role of vasodilator prostaglandins in the aorta was increased and the role of endothelium-derived hyperpolarizing factor and response of the AT1-R and AT2-R to Ang-II was decreased in pregnant saline infused rats as compared with non-pregnant rats. These changes were not observed during preeclampsia. CONCLUSION: Pregnancy induced adaptations in endothelial function, which were not observed in the rat model for preeclampsia. This role of lack of pregnancy induced endothelial adaptation in the pathophysiology of experimental preeclampsia needs further investigation.

Flash pulmonary edema during cesarean section in a woman with preeclampsia.

BACKGROUND: Pulmonary edema may complicate preeclampsia. We report intraoperative flash pulmonary edema in a preeclamptic woman with Rendu-Osler-Weber syndrome. CASE: The patient was admitted at 33(+6) weeks gestation with preeclampsia. After rapid sequence induction and endotracheal intubation for cesarean section, flash pulmonary edema developed without evidence of cardiac dysfunction. She was mechanically ventilated and treated with furosemide. Following brisk diuresis she was extubated the next day and discharged on postoperative day 9 in good clinical condition. CONCLUSION: Endotracheal intubation for general anesthesia can cause acutely increased blood pressure, which, with concomitant low oncotic pressure, we believe contributed to intraoperative flash pulmonary edema. We present this case to raise awareness of this complication when general anesthesia is used for cesarean section in preeclampsia.

Visual disturbances in (pre)eclampsia.

UNLABELLED: This review aims to summarize existing information concerning visual disturbances in (pre) eclampsia that have been described in the literature. Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality worldwide. Visual disturbances in (pre)eclampsia seem to be frequent phenomena. Therefore, the obstetrician/gynecologist may encounter women with serious, and sometimes debilitating, pathology of the visual pathways. Established ophthalmic entities associated with (pre)eclampsia are cortical blindness, serous retinal detachment, Purtscher-like retinopathy, central retinal vein occlusions, and retinal or vitreous hemorrhages. Ensuing visual symptoms include blurry vision, diplopia, amaurosis fugax, photopsia, and scotomata, including homonymous hemianopsia. In general, aside from lowering the blood pressure and preventing (further) seizures with magnesium sulfate, no specific therapy seems indicated for (pre)eclamptic women who experience visual changes. Although in most cases visual acuity returns to normal within weeks to months after the onset of symptoms, rarely permanent visual impairment can occur. Health care providers such as emergency room physicians, obstetricians, family physicians, neurologists, and ophthalmologists should be aware that acute onset of visual symptoms in pregnant women can be the first sign of (pre)eclampsia. Given that visual changes are a diagnostic criterion for severe preeclampsia, obstetricians should appreciate the significance of these changes and discuss appropriate diagnostic options with the ophthalmologist. Affected women can be reassured that most cases are transient. TARGET AUDIENCE: Obstetricians and gynecologists, ophthalmologists, neurologists, family physicians, emergency room physicians LEARNING OBJECTIVES: After completing this CME activity, obstetricians and gynecologists should be better able to classify visual disturbances at an early stage during pregnancy, interpret acute onset of visual disturbances as the first sign of preeclampsia, and evaluate possible residual visual symptoms during follow-up.

Long-term visual functioning after eclampsia.

OBJECTIVE: Complete neurocognitive recovery after eclampsia has been questioned with the expression of neurocognitive deficits by affected women and demonstration of cerebral white matter lesions on magnetic resonance imaging years after eclampsia. We hypothesized that formerly eclamptic women may experience impaired vision-related quality of life (QOL) and visual field loss as a result of the presence of such lesions in the cerebral visual areas. METHODS: Using the National Eye Institute Visual Function Questionnaire-39/Nederlands questionnaire, vision-related QOL was compared between formerly eclamptic women and control participants after normotensive pregnancies. Furthermore, in formerly eclamptic women, visual fields were assessed using automated perimetry, and presence of white matter lesions was evaluated using cerebral magnetic resonance imaging. Presence of a relationship between these lesions and National Eye Institute Visual Function Questionnaire-39/Nederlands scores was estimated. RESULTS: Forty-seven formerly eclamptic women and 47 control participants participated 10.1±5.2 and 11.5±7.8 years after their index pregnancy, respectively. Composite scores and 4 out of 12 National Eye Institute Visual Function Questionnaire-39/Nederlands subscale scores were significantly lower in formerly eclamptic women than in control participants (P<.01 for composite scores). This could not be explained by visual field loss, because all formerly eclamptic women who underwent perimetry (n=43) demonstrated intact visual fields. White matter lesions were present in 35.7% of formerly eclamptic women who underwent magnetic resonance imaging (n=42) and were associated with lower vision-related QOL scores (P<.05 for composite scores). CONCLUSION: Formerly eclamptic women express lower vision-related QOL than control participants, which seemed at least partly related to the presence of white matter lesions. However, such women do not have unconscious visual field loss. Vision-related QOL impairment expressed by formerly eclamptic women may therefore be related to problems with higher-order visual functions. LEVEL OF EVIDENCE: II.