Rachael Morris

Posterior reversible encephalopathy syndrome in 46 of 47 patients with eclampsia.

OBJECTIVE We sought to investigate the concurrence of posterior reversible encephalopathy syndrome (PRES) with eclampsia and to describe the obstetric, radiological, and critical care correlates. STUDY DESIGN This was a single-center, 2001-2010 retrospective cohort study of all patients with eclampsia who underwent neuroimaging via magnetic resonance imaging (MRI) or computerized tomography (CT) with or without contrast. RESULTS Forty-six of 47 of eclamptic patients (97.9%) revealed PRES on neuroimaging using 1 or more modalities: MRI without contrast, 41 (87.2%); MRI with contrast, 27 (57.4%); CT without contrast, 16 (34%); CT with contrast, 7 (14.8%); and/or magnetic resonance angiography/magnetic resonance venography, 2 (4.3%). PRES was identified within the parietal, occipital, frontal, temporal, and basal ganglia/brainstem/cerebellum areas of the brain. Eclampsia occurred antepartum in 23 patients and postpartum in 24 patients. Headache was the most common presenting symptom (87.2%) followed by altered mental status (51.1%), visual disturbances (34%), and nausea/vomiting (19.1%). Severe systolic hypertension was present in 22 patients (47%). CONCLUSION The common finding of PRES in patients with eclampsia suggests that PRES is a core component of the pathogenesis of eclampsia. Therapy targeted at prevention or reversal of PRES pathogenesis may prevent or facilitate recovery from eclampsia.

Maternal hemodynamics by thoracic impedance cardiography for normal pregnancy and the postpartum period.

OBJECTIVE: To establish normative impedance cardiography values for the second half of pregnancy and up to 48 hours postpartum after either vaginal or cesarean delivery. METHODS: A single-center prospective observational institutional review board-approved study of normotensive women (n=168) using thoracic impedance cardiography performed at specific times during gestation. Antepartum testing was performed at three time periods: 20–27 weeks, 28–33 weeks, and 34–40 weeks of gestation. Postpartum testing was undertaken after the immediate puerperium at 6–23 hours and 24–48 hours after vaginal or cesarean delivery. Data analysis was performed using STATA software; data are expressed as mean±standard deviation. RESULTS: All seven of the patient groups studied were comparable with regard to demographic features; 80% of the study participants were African American. Group means obtained between 20 and 40 weeks of gestation and postpartum after vaginal and cesarean delivery fell within the “normal range” of the hemodynamic graph that was developed to associate mean arterial pressure and systemic vascular resistance. The thoracic fluid content group means in both vaginal and cesarean delivery groups were higher than the antepartum patient groups. The thoracic fluid content mean after cesarean delivery at 48 hours is significantly higher than the mean value recorded between 20 and 27 weeks of gestation (P<.05). The systemic vascular resistance systemic vascular resistance means in each of the postpartum groups were significantly higher than the late second-trimester group means recorded at 20–27 weeks of gestation (P<.05). CONCLUSION: The normative values reported in this investigation can be used to interpret and assess similarly tested patients with hypertensive or otherwise complicated pregnancy. LEVEL OF EVIDENCE: III

Hypertension, inflammation and T lymphocytes are increased in a rat model of HELLP syndrome

Objective: An animal model of hemolysis, elevated liver enzymes, low platelet count (HELLP) was used to determine if T lymphocytes accompany hypertension and increased inflammatory cytokines. Methods: sFlt-1 (4.7 µg/kg/day) and sEndoglin (7 µg/kg/day) were infused into normal pregnant rats (HELLP rats) for 8 days. Results: HELLP was associated with increased mean arterial pressure (p = 0.0001), hemolysis (p = 0.044), elevated liver enzymes (p = 0.027), and reduced platelets (p = 0.035). HELLP rats had increased plasma levels of TNFα (p = 0.039), IL-6 (p = 0.038) and IL-17 (p = 0.04). CD4+ and CD8+ T lymphocytes were increased. Conclusion: These data support the hypothesis that T cells are associated with hypertension and inflammation.

Hypertension in an Animal Model of HELLP Syndrome is Associated With Activation of Endothelin 1

Women with hypertensive forms of pregnancy such as hemolysis–elevated liver enzymes–low platelet syndrome have increased circulating endothelin 1; however, the relationship between hypertension and endothelin 1 has not been studied. Using an animal model, we sought to determine whether there was an increased activation/dysfunction of endothelin 1, the effect of endothelin 1 receptor-A blockade on hypertension and other manifestations of hemolysis, elevated liver enzymes, and low platelets syndrome. On gestational day 12, timed-pregnant rats were infused with soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEndoglin; 4.7 and 7 µg/kg) via mini-osmotic pumps for 8 days. A subset of rats were treated with receptor-A antagonist (ABT-627, 5mg/kg) for 8 days. Rats with hemolysis-elevated liver enzymes-low platelet syndrome had significantly increased hypertension (P = .0001), circulating endothelin 1 (P = .03), and a significant 3.3- and 7.2-fold increase in preproendothelin messenger RNA (mRNA) expression in the placenta and liver (P = .01 and .04). Urinary protein:creatinine ratio was significantly increased in these animals (P = .0007), and circulating factors from these rats stimulated a significant increase in endothelial cell secretion of endothelin 1 (P = .001) in an in vitro assay. Blockade of the endothelin 1 receptor A significantly decreased hypertension (P = .001), circulating endothelin 1, and interleukin 17 (P = .004 and .003), placental preproendothelin mRNA expression (P = .016), and urinary protein:creatinine ratio (P = .007) in rats with hemolysis–elevated liver enzymes–low platelet syndrome. Blockade of the endothelin 1 receptor A significantly decreased hemolysis (P = .009), liver enzymes (P = .011), and significantly increased platelet levels (P = .03) and decreased circulating CD4+ and CD8+ T lymphocytes (P = .0004 and .0001) in rats infused with sFlt-1 and sEndoglin. These data support the hypothesis that endothelin 1 activation has a critical role in pathophysiology of as hemolysis–elevated liver enzymes–low platelet syndrome.

Plasma From Patients With HELLP Syndrome Increases Blood–Brain Barrier Permeability

Circulating inflammatory factors and endothelial dysfunction have been proposed to contribute to the pathophysiology of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. To date, the occurrence of neurological complications in these women has been reported, but few studies have examined whether impairment in blood–brain barrier (BBB) permeability or cerebrovascular reactivity is present in women having HELLP syndrome. We hypothesized that plasma from women with HELLP syndrome causes increased BBB permeability and cerebrovascular dysfunction. Posterior cerebral arteries from female nonpregnant rats were perfused with 20% serum from women with normal pregnancies (n = 5) or women with HELLP syndrome (n = 5), and BBB permeability and vascular reactivity were compared. Plasma from women with HELLP syndrome increased BBB permeability while not changing myogenic tone and reactivity to pressure. Addition of the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester caused constriction of arteries that was not different with the different plasmas nor was dilation to the NO donor sodium nitroprusside different between the 2 groups. However, dilation to the small- and intermediate-conductance, calcium-activated potassium channel activator NS309 was decreased in vessels exposed to HELLP plasma. Thus, increased BBB permeability in response to HELLP plasma was associated with selective endothelial dysfunction.

Impedance cardiography assessed treatment of acute severe pregnancy hypertension: a randomized trial

Abstract Objective: Using noninvasive bedside impedance cardiography (ICG), we compared the effectiveness and the hemodynamic impact of intravenous labetalol versus hydralazine for the reduction of acute-onset severe hypertension to ACOG-recommended blood pressure levels (ACOG Committee Opinion 514). Study design: In this prospective randomized pilot study of acutely severe systolic hypertension (≥160 mmHg), pregnant women received either labetalol (L) or hydralazine (H) intravenously and underwent thoracic ICG before and after treatment. Data analysis were performed using STATA software (StataCorp LP, College Station, TX); data are expressed as mean ± SD. Results: About 29 patients completed the study. There was no significant difference in mean arterial pressure (MAP) between groups [H = 119.4 mmHg, L = 117.7 mmHg, mean difference (MD) = 1.73); the estimated MD between baseline and follow-up ICG was −9.17 (p = 0.001, 95% CI: −14.39 to −3.95). There were no significant differences in total peripheral resistance (TPR) between groups (H = 1771.3, L = 1976.97, MD = 205.62) or cardiac output (CO) between groups (H = 5.7, L = 5.1, MD = 0.64) or a significant MD between these at baseline and follow-up. Conclusion: Both drugs performed similarly to achieve ACOG-recommended initial blood pressure reduction safely without side effects or excessive acute hemodynamic profile correction toward normal pregnancy values.

Solid fibrous tumor of the liver: a case in pregnancy

Background: Solid fibrous tumor (SFT) is a rare neoplasm, preferentially involving the pleura, rarely the liver. Case: A primigravida between 13–15 weeks gestation developed nausea, vomiting, and abdominal pain. Imaging revealed a large, complex septated mass filling the abdomen and pelvis. At surgery a firm, lobular mass involved in the inferior aspect of the right liver lobe. Open cholecystectomy and hepatic segmentectomy were performed; confirmatory immunohistochemical staining was positive for SFT. Conclusion: A rapidly growing abdominopelvic mass during pregnancy may be a SFT. The diagnosis and perioperative management of SFT presents multiple challenges to the obstetrician.

Attenuation of oxidative stress and hypertension in an animal model of HELLP syndrome

ABSTRACT HELLP (hemolysis elevated liver enzyme low platelet) syndrome is associated with hypertension, inflammation, oxidative stress and endothelial activation. The objective of this study was to determine if oxygen scavenging or endothelin A receptor antagonism improved hypertension and oxidative stress. sFlt‐1 and sEndoglin were infused via mini‐osmotic pump into normal pregnant rats (NP) on gestational day 12 to create HELLP syndrome. On gestational day 18 arterial catheters were inserted and on gestational day 19 mean arterial pressure was analyzed in rats; serum, urine and tissues were collected for molecular analysis. HELLP rats had significantly increased MAP compared to control normal pregnant rats (P<0.0005). Endothelin A receptor antagonism via ABT‐627 and Tempol, superoxide dismutase mimetic, were administered to a subset of normal pregnant and HELLP rats beginning on gestational day 13 and attenuated mean arterial pressure in HELLP rats (P<0.05; P<0.005). There were no statistically significant differences in mean arterial pressure between NP+ETA Receptor or NP+Tempol treated rats and NP rats (P=0.22). Endothelin A receptor blockade significantly decreased HELLP induced isoprostane excretion (P<0.0005), placental and hepatic reactive oxygen species (P<0.05; P<0.0005) and increased placental total antioxidant capacity (P<0.005) compared to untreated HELLP rats. Similar results in isoprostane (P<0.005), hepatic reactive oxygen species (P<0.05) and placental total antioxidant capacity (P<0.05) were seen in HELLP rats treated with Tempol or Endothelin A receptor antagonist vs. untreated HELLP rats. These data demonstrated a role for oxidative stress in contributing to the hypertension, placental and liver damage that is seen in HELLP syndrome.

Dysregulation of the Fas/FasL system in an experimental animal model of HELLP syndrome

INTRODUCTION Placental FasL is up-regulated in women with HELLP (hemolysis elevated liver enzyme and low platelet) syndrome and has been proposed to contribute to the liver damage seen in these patients. OBJECTIVE This study aimed to determine if an experimental rodent model of HELLP also had dysregulation of Fas/FasL compared to normal pregnant (NP) rats. We also set out to determine if blockade of the endothelin system regulated Fas/FasL expression in HELLP rats. STUDY DESIGN On gestational day (GD) 12, sEng (7ug/kg) and sFlt-1 (4.7ug/kg) infusion began via mini-osmotic pump into NP rats. On GD19 plasma and tissue were collected and FasL and Fas were measured via enzyme linked immunosorbent assay and gene expression via real-time PCR. RESULTS HELLP rats had significantly more circulating and placental FasL compared to NP rats, whereas hepatic FasL was decreased and placental Fas was increased compared to NP rats. Administration of an endothelin A receptor antagonist (ETA) beginning on GD12 significantly decreased placental expression of Fas in HELLP rats. Liver mRNA transcript of Fas was significantly increased in HELLP rats compared to NP rats. CONCLUSION These data suggest that rats in this experimental model of HELLP syndrome have abnormal expression of the Fas/FasL system. Future studies will examine the sources of Fas/FasL dysregulation in this model and if blockade could reduce some of the inflammation and hypertension associated with HELLP syndrome.