Report from a text-based blood pressure monitoring prospective cohort trial among postpartum women with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy are a main cause of maternal morbidity and mortality in the United States and worldwide, and it is estimated that approximately 60% of maternal deaths in the United States occur during the postpartum period. The utilization of telehealth modalities such as home blood pressure monitoring has shown improvement in blood pressure control and adherence with follow up visits. Our study sought to determine if standardized education improved patient hypertension knowledge and if this when combined with home blood pressure telemonitoring increased participants' postpartum self-blood pressure monitoring and postpartum visit attendance. METHODS: This is an Institutional Review Board approved prospective cohort study conducted at the University of Mississippi Medical Center. Women with a hypertensive disorder of pregnancy who met the inclusion criteria and provided written informed consent to participate were enrolled. Participants received a baseline pre-education questionnaire designed to assess their knowledge of their hypertensive diagnosis, hypertension management, and postpartum preeclampsia (PreE). Participants then received standard education, a blood pressure monitor, and were scheduled a follow-up visit during the first 10 days following discharge. Remote home blood pressure monitoring was performed via text messages and voice calls for 6-weeks postpartum. At the conclusion of the study, participants repeated their original questionnaire. RESULTS: 250 women provided informed consent to participate in the study and were included in this analysis. Relative to the baseline survey, there was a significant increase (p = 0.0001) in the percentage of correct responses. There was not an association between study engagement and percentage of correct responses on end of study questionnaire (p = 0.33) or postpartum visit attendance (p = 0.69). Maternal age was found to drive study engagement, even when adjusted for community-level distress (p = 0.03) and maternal race (p = 0.0002). CONCLUSION: Implementing a standardized postpartum education session was associated with improvement in patient's knowledge. Further studies are needed with more longitudinal follow up to assess if this program would also result in improved long-term outcomes and decreased hospital readmission rates. TRIAL REGISTRATION: NCT04570124.

Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial.

OBJECTIVES: To determine whether rate of severe intraventricular hemorrhage (IVH) or death among preterm infants receiving placental transfusion with UCM is noninferior to delayed cord clamping (DCC). METHODS: Noninferiority randomized controlled trial comparing UCM versus DCC in preterm infants born 28 to 32 weeks recruited between June 2017 through September 2022 from 19 university and private medical centers in 4 countries. The primary outcome was Grade III/IV IVH or death evaluated at a 1% noninferiority margin. RESULTS: Among 1019 infants (UCM n = 511 and DCC n = 508), all completed the trial from birth through initial hospitalization (mean gestational age 31 weeks, 44% female). For the primary outcome, 7 of 511 (1.4%) infants randomized to UCM developed severe IVH or died compared to 7 of 508 (1.4%) infants randomized to DCC (rate difference 0.01%, 95% confidence interval: (-1.4% to 1.4%), P = .99). CONCLUSIONS: In this randomized controlled trial of UCM versus DCC among preterm infants born between 28 and 32 weeks' gestation, there was no difference in the rates of severe IVH or death. UCM may be a safe alternative to DCC in premature infants born at 28 to 32 weeks who require resuscitation.

Long QT syndrome-associated calmodulin variants disrupt the activity of the slowly activating delayed rectifier potassium channel.

Calmodulin (CaM) is a highly conserved mediator of calcium (Ca2+ )-dependent signalling and modulates various cardiac ion channels. Genotyping has revealed several CaM mutations associated with long QT syndrome (LQTS). LQTS patients display prolonged ventricular recovery times (QT interval), increasing their risk of incurring life-threatening arrhythmic events. Loss-of-function mutations to Kv7.1 (which drives the slow delayed rectifier potassium current, IKs, a key ventricular repolarising current) are the largest contributor to congenital LQTS (>50% of cases). CaM modulates Kv7.1 to produce a Ca2+ -sensitive IKs, but little is known about the consequences of LQTS-associated CaM mutations on Kv7.1 function. Here, we present novel data characterising the biophysical and modulatory properties of three LQTS-associated CaM variants (D95V, N97I and D131H). We showed that mutations induced structural alterations in CaM and reduced affinity for Kv7.1, when compared with wild-type (WT). Using HEK293T cells expressing Kv7.1 channel subunits (KCNQ1/KCNE1) and patch-clamp electrophysiology, we demonstrated that LQTS-associated CaM variants reduced current density at systolic Ca2+ concentrations (1 µm), revealing a direct QT-prolonging modulatory effect. Our data highlight for the first time that LQTS-associated perturbations to CaM's structure impede complex formation with Kv7.1 and subsequently result in reduced IKs. This provides a novel mechanistic insight into how the perturbed structure-function relationship of CaM variants contributes to the LQTS phenotype. KEY POINTS: Calmodulin (CaM) is a ubiquitous, highly conserved calcium (Ca2+ ) sensor playing a key role in cardiac muscle contraction. Genotyping has revealed several CaM mutations associated with long QT syndrome (LQTS), a life-threatening cardiac arrhythmia syndrome. LQTS-associated CaM variants (D95V, N97I and D131H) induced structural alterations, altered binding to Kv7.1 and reduced IKs. Our data provide a novel mechanistic insight into how the perturbed structure-function relationship of CaM variants contributes to the LQTS phenotype.

A Systematic Review of the Safety and Efficacy of Inferior Vena Cava Stenting.

OBJECTIVE: Inferior vena cava (IVC) stenting may provide benefit to patients with symptomatic obstruction; however, there are no devices currently licensed for use in the IVC and systematic reviews on the topic are lacking. The aim of this study was to carry out a systematic review of the literature and meta-analysis to investigate the safety and efficacy of IVC stenting in all adult patient groups. DATA SOURCES: The Medline and Embase databases were searched for studies reporting outcomes for safety and effectiveness of IVC stenting for any indication in series of 10 or more patients. REVIEW METHODS: A systematic review of the literature was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Thirty-three studies were included describing 1 575 patients. Indications for stenting were malignant IVC syndrome (229 patients), thrombotic disease (807 patients), Budd-Chiari syndrome (501 patients), and IVC stenosis post liver transplantation (47 patients). The male:female ratio was 2:1 and the median age ranged from 30 to 61 years. The studies included were not suitable for formal meta-analysis as 30/33 were single centre retrospective studies with no control groups and there was considerable inconsistency in outcome reporting. There was significant risk of bias in 94% of studies. Median reported technical success was 100% (range 78 - 100%), primary patency was 75% (38 - 98%), and secondary patency was 91.5% (77 - 100%). Major complications were pulmonary embolism (three cases), stent migration (12 cases), and major bleeding (15 cases), and there were three deaths in the immediate post-operative period. Most studies reported improvement in clinical symptoms but formal reporting tools were not used consistently. CONCLUSION: The evidence base for IVC stenting consists of predominantly single centre, retrospective, observational studies that have a high risk of bias. Nonetheless the procedure appears safe with few major adverse events, and studies that reported clinical outcomes demonstrate improvement in symptoms and quality of life. Randomised controlled trials and prospective registry based studies with larger patient numbers and standardised outcome are required to improve the evidence base for this procedure.

COVID-19 Not Hypertension or Diabetes Increases the Risk of Preeclampsia among a High-Risk Population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has been associated with greater morbidity and increased mortality in certain populations, such as those with chronic medical conditions, the elderly, and pregnant women. Our goal was to determine if COVID-19 infection during pregnancy increased the risk of preeclampsia in a population of women with increased risk factors for preeclampsia. We present a prospective observational matched case-control study of 100 deliveries with confirmed SARS-CoV2. Specifically, we investigated the maternal and neonatal outcomes in a high-risk population of pregnant women. Among women with COVID-19, the severity of symptoms was associated with the incidence of preeclampsia, but not with pre-existing diabetes or hypertension. Women with more severe symptoms were more likely to delivery pre-term with smaller babies. After adjusting for diabetes, hypertensive women with COVID-19 had an increased risk of preeclampsia aOR4.3 [1.5,12.4] compared to non-hypertensive women with COVID-19. After adjusting for hypertension, women with diabetes and COVID-19 had an increased risk of preeclampsia aOR3.9 [1.2,12.5]. This relationship was not seen among women without COVID-19. For women who had pre-existing diabetes or hypertension, the risk of developing preeclampsia was only increased if they were also diagnosed with COVID-19, suggesting that in our population of women the risk of preeclampsia is not associated with pre-existing diabetes or hypertension.

Preeclampsia and COVID-19: the Role of Inflammasome Activation.

PURPOSE OF REVIEW: It is well established that controlled immune activation and balance is critical for women's reproductive health and successful pregnancy outcomes. Research in recent decades in both clinical and animal studies has demonstrated that aberrant immune activation and inflammation play a role in the development and progression of women's reproductive health and pregnancy-related disorders. Inflammasomes are multi-protein cytoplasmic complexes that mediate immune activation. In this review, we summarize current knowledge on the role of inflammasome activation in pregnancy-related disorders. RECENT FINDINGS: Increased activation of inflammasome is associated with multiple women's health reproductive disorders and pregnancy-associated disorders, including preeclampsia (PreE). Inflammasome activation is also associated with the novel coronavirus disease 2019 (COVID-19) disease caused by the SARS-Cov-2 virus. We and others have observed a positive association between increased PreE incidences with the onset of the COVID-19 pandemic. Here, we present our recent data indicating increased inflammasome activation, represented by caspase-1 activity, in women with COVID-19 and PreE compared to normotensive pregnant women COVID-19. The role of inflammation in pregnancy-related disorders is an area of intense research interest. With the onset of the COVID-19 pandemic and the associated increase in PreE observed clinically, there is a greater need to identify mechanisms of pathophysiology and targets to treat this maternal disorder. Inflammasome activation is associated with PreE and COVID-19 infection and may hold therapeutic potential to improve outcomes associated with PreE and curb the morbidity attributed to PreE.

Performance of Open and Closed Cell Laser Cut Nitinol Stents for the Treatment of Chronic Iliofemoral Venous Outflow Obstruction in Patients Treated at a Single Centre.

OBJECTIVE: A number of dedicated self expanding nitinol stents have been developed for use in the venous system, with both open cell (OC) and closed cell (CC) designs available. Data comparing these different designs are lacking. The objective of this study was to evaluate outcomes in patients treated with open and closed cells for unilateral chronic iliac vein obstruction. METHODS: A single centre retrospective cohort study was conducted, including all patients treated with a dedicated nitinol venous stent between 2014 and 2019. Stent patency and details of re-interventions (including lysis, venoplasty, reinforcement, extension, arteriovenous fistula formation) were examined in the first post-operative year. Subgroup analysis described outcomes for patients treated with OC and CC stents ending above the inguinal ligament and those who required extension into the common femoral vein. Cox regression analysis was used to identify factors associated with loss of primary patency. RESULTS: A total of 207 patients were included (OC 100 patients, CC 107 patients). There was no significant difference between the groups for age (OC 42 years, CC 44 years); gender (OC and CC 67% female); presence of post-thrombotic lesions (OC 71%, CC 73%); stenting across the inguinal ligament (OC 58%, CC 56%), or presence of inflow disease (OC 49%, CC 47%). Primary and cumulative patency at 12 months were similar between groups (primary: OC 63%, CC 65%; cumulative: OC 93%, CC 90%). Patients with a CC stent across the inguinal ligament had a greater risk of needing multiple re-interventions at one year compared with those with an OC stent (odds ratio 2.84, 95% confidence interval [CI] 1.16 - 6.9) but overall, the only factor significantly associated with loss of primary patency was inflow vessel disease (hazard ratio 3.39, 95% CI 1.73 - 6.62, p < .001). CONCLUSION: OC and CC dedicated nitinol venous stents were observed to perform similarly in terms of patency and symptom improvement at one year. Disease of the inflow vessels was the most important factor associated with a loss of stent patency irrespective of stent design.

Medium-term outcomes after inferior vena cava reconstruction for acute and chronic deep vein thrombosis and retroperitoneal fibrosis.

OBJECTIVE: In the present study, we evaluated the technical and clinical outcomes after endovascular inferior vena cava (IVC) reconstruction in patients with nonmalignant obstruction. METHODS: The preoperative, procedural, and follow-up medical records and imaging studies were retrospectively reviewed for 59 consecutive patients who had undergone endovascular IVC reconstruction for nonmalignant obstruction from February 2014 to January 2019. The patients were classified into three groups according to the quality of their infrainguinal inflow vessels. The outcomes measured were the primary, primary-assisted, and secondary patency rates, reintervention rates, and symptomatic resolution. RESULTS: The indications for treatment were post-thrombotic syndrome (n = 41), acute deep vein thrombosis (n = 12), and retroperitoneal fibrosis (n = 6). The median patient age was 37 years, 11 months, 71.2% were men, and 32.2% had a diagnosis of thrombophilia, with no significant difference in these demographics between the three inflow groups. The median follow-up duration was 2 years, 3 months (range, 6 months to 6 years, 5 months). The whole-cohort primary patency was 91.2%, 71.0%, and 24.1% at 1, 3, and 5 years, respectively. Secondary patency was 76.7% at 1 year and 66.4% at both 3 and 5 years. Inflow group A (no post-thrombotic disease in the femoral or deep femoral veins) demonstrated significantly higher primary patency compared with group B (stenotic disease in one or two infrainguinal inflow veins; P = .009) and significantly higher secondary patency than for both groups B (P = .008) and C (all three infrainguinal inflow veins had stenosed or femoral and/or deep femoral vein occlusion was present; P = .04). In post-thrombotic syndrome patients, the Villalta scores had decreased from a mean of 14.2 to 8.1 at 1 year and 6.8 at 2 years, and the Venous Insufficiency Epidemiological and Economic Study Quality of Life score had improved from a mean of 19.8 to 54.1 and 57.3 at 1 and 2 years, respectively. In the patients with acute deep vein thrombosis, the Villalta score was 2.8 at 1 year and 0 at 2 years. In the patients with retroperitoneal fibrosis, the Venous Insufficiency Epidemiological and Economic Study Quality of Life score had improved from a mean of 25.3 at baseline to 44 at 6 months. CONCLUSIONS: Endovascular IVC reconstruction for nonmalignant obstruction can achieve good patency and clinical improvement, although the outcomes were poorer for patients with post-thrombotic disease of the femoral and deep femoral veins.

A Systematic Review and Meta-Analysis of 12-Month Patency After Intervention for Iliofemoral Obstruction Using Dedicated or Non-Dedicated Venous Stents.

BACKGROUND: Endovascular stenting of the deep venous system has been proposed as a method to treat patients with symptomatic iliofemoral outflow obstruction. The purpose of this systematic review and meta-analysis was to compare the effectiveness of this treatment at 1-year following the development of dedicated venous stents. METHOD AND RESULTS: We searched MEDLINE and EMBASE for studies evaluating the effectiveness of venous stent placement. Data were extracted by disease pathogenesis: non-thrombotic iliac vein lesions (NIVL), acute thrombotic (DVT), or post-thrombotic syndrome (PTS). Main outcomes included technical success, stent patency at 1 year and symptom relief. A total of 49 studies reporting outcomes in 5154 patients (NIVL, 1431; DVT, 950; PTS, 2773) were included in the meta-analysis. Technical success rates were comparable among groups (97%-100%). There were no periprocedural deaths. Minor bleeding was reported in up to 5% of patients and major bleeding in 0.5% upon intervention. Transient back pain was noted in 55% of PTS patients following intervention. There was significant heterogeneity between studies reporting outcomes in PTS patients. Primary and cumulative patency at 1 year was: NIVL-96% and 100%; DVT-91% and 97%; PTS (stents above the ligament)-77% and 94%, and; PTS (stents across the ligament)-78% and 94%. There were insufficient data to compare patency outcomes of dedicated and nondedicated venous stents in patients with acute DVT. In NIVL and PTS patients, stent patency was comparable at 1 year. There was inconsistency in the use of validated tools for the measurement of symptoms before and after intervention. When reported, venous claudication, improved in 83% of PTS patients and 90% of NIVL patients, and ulcer healing occurred in 80% of PTS patients and 32% of NIVL patients. CONCLUSIONS: The first generation of dedicated venous stents perform comparably in terms of patency and clinical outcomes to non-dedicated technologies at 1 year for the treatment of patients with NIVL and PTS. However, significant heterogeneity exists between studies and standardized criteria are urgently needed to report outcomes in patients undergoing deep venous stenting.

Editor's Choice - Systematic Review and Meta-Analysis of Sex Specific Differences in Adverse Events After Open and Endovascular Intact Abdominal Aortic Aneurysm Repair: Consistently Worse Outcomes for Women.

OBJECTIVE: Previously, reports have shown that women experience a higher mortality rate than men after elective open (OAR) and endovascular (EVAR) repair of abdominal aortic aneurysm (AAA). With recent improvements in overall AAA repair outcomes, this study aimed to identify whether sex specific disparity has been ameliorated by modern practice, and to define sex specific differences in peri- and post-operative complications and pre-operative status; factors which may contribute to poor outcome. METHODS: This was a systematic review, meta-analysis, and meta-regression of sex specific differences in 30 day mortality and complications conducted according to PRISMA guidance (Prospero registration CRD42020176398). Papers with ≥ 50 women, reporting sex specific outcomes, following intact primary AAA repair, from 2000 to 2020 worldwide were included; with separate analyses for EVAR and OAR. Data sources were Medline, Embase, and CENTRAL databases 2005 - 2020 searched using ProQuest Dialog. RESULTS: Twenty-six studies (371 215 men, 65 465 women) were included. Meta-analysis and meta-regression indicated that sex specific odds ratios (ORs) for 30 day mortality were unchanged from 2000 to 2020. Mortality risk was higher in women for OAR and more so for EVAR (OR [95% CI] 1.49 [1.37 - 1.61]; 1.86 [1.59 - 2.17], respectively) and this remained following multivariable risk adjustment. Transfusion, pulmonary complications, and bowel ischaemia were more common in women after OAR and EVAR (OAR: ORs 1.81 [1.60 - 2.04], 1.40 [1.28 - 1.53], 1.54 [1.36 - 1.75]; EVAR: ORs 2.18 [2.08 - 2.29] 1.44 [1.17 - 1.77], 1.99 [1.51 - 2.62], respectively). Arterial injury, limb ischaemia, renal and cardiac complications were more common in women after EVAR (ORs 3.02 [1.62 - 5.65], 2.13 [1.48 - 3.06], 1.46 [1.22 - 1.72] and 1.19 [1.03 - 1.37], respectively); the latter was associated with greater mortality risk on meta-regression. CONCLUSION: Increased mortality risk for women following AAA repair remains. Women had a higher incidence of transfusion, pulmonary and bowel complications after EVAR and OAR. Higher mortality risk ratios for EVAR may result from cardiac complications, additional arterial injury, and embolisation, leading to renal and limb ischaemia. These findings indicate possible causes for observed outcome disparities and targets for quality improvement.

Quality of life outcomes for patients undergoing venous stenting for chronic deep venous disease.

OBJECTIVE: The objective of the study was to evaluate change in venous disease-specific quality of life (QoL) after iliac vein stenting for chronic venous outflow obstruction. METHODS: We performed a retrospective analysis of all Venous Insufficiency Epidemiological and Economic Study - Quality of Life/Symptoms (VEINES-QoL/Sym) questionnaires completed at a single-center between 2016 and 2019 by patients treated with iliac vein stenting for chronic venous outflow obstruction. Patients were asked to complete the questionnaire at baseline (before stenting) and at subsequent follow-up appointments (after stenting), at 6, 12, 24, and 36 months. The Villalta score was recorded by a venous nurse specialist. The initial unpaired analysis compared all completed VEINES-QoL/Sym and Villalta scores at baseline to all follow-up time-points, and then compared them individually between baseline and each follow-up point. A secondary paired analysis included data only from patients who had completed the questionnaire at baseline and at least one follow-up. RESULTS: A total of 385 questionnaires from 187 patients who completed the VEINES-QoL/Sym between 2016 and 2019 were included. The median follow-up was 12 months, 127 patients (68%) were female, and 148 (79%) were treated for post-thrombotic syndrome. The median VEINES-QoL score at baseline was 35.69 (interquartile range [IQR], 20.85-46.67). Significant improvement was observed postoperatively and sustained throughout the study period (6 months, 64.81 [IQR, 38.12-83.88]; 12 months, 60.52 [IQR, 33.6-82.3]; 24 months, 60.37 [IQR, 34.31-80.65]; 36 months, 55.98 [IQR, 39.18-81.47]). The VEINES-Sym scores demonstrated similar improvement. A secondary analysis of paired baseline/follow-up data from 61 patients confirmed significant improvement from baseline for VEINES-QoL (6 months +26.45; 12 months, +25.81; 24 months, +30.09; P ≤ .0001), VEINES-Sym (6 months, +23.86; 12 months, +20.43; 24 months, +27.55; P > .001), and Villalta scores (6 months, -3.7; 12 months, -4.2; 24 months, -6.4; P < .0001). The median Villalta score was 14 (IQR, 10-16). This score improved to 9 (IQR, 5-13) at 6 months of follow-up; to 8 (IQR, 5-11) at 12 months; to 7 (IQR, 4-12) at 24 months; and to 6 (IQR, 3.75-10.25) at 36 months (P ≤ .0001). Good correlation between the Villalta and both VEINES-QoL and SYM scores was observed at follow-up (r = 0.69 and r = 0.71, respectively; P < .0001). CONCLUSIONS: Venous disease-specific QoL improves and severity of post-thrombotic syndrome is decreased after iliac vein stenting for chronic venous outflow obstruction. These improvements are sustained at 36-month follow-up.

Device profile of the Vici venous stent for chronic iliofemoral venous obstruction recanalization: overview of its safety and efficacy.

Introduction: Endovenous stenting is being increasingly used for the management of iliofemoral venous outflow obstruction due to thrombotic or non-thrombotic iliac vein lesions (NIVL). Dedicated venous stents have replaced re-purposed arterial stents but there are limited data on their relative safety and efficacy.Areas covered: This review looks at the available literature on the safety and efficacy of the Veniti Vici Venous stent (Boston Scientific), a specific venous stent, and compares its outcomes with the other venous stents that are currently available. Reported outcomes include patency, clinical efficacy, and the number of adverse events.Expert opinion: The initial clinical trials of the Vici venous stent have shown both good clinical and safety outcomes at 12-24 months follow-up. Longer follow-up data are pending and further trials comparing available stents are required. Current evidence supports its use in the management of deep venous reconstruction, especially in occlusive post-thrombotic disease. Patients should, however, be made aware of the paucity of long-term data and the need for monitoring within a dedicated surveillance program following stent placement.

Iliocaval Venous Obstruction, Cardiac Preload Reserve and Exercise Limitation.

Cardiac output during exercise increases by as much as fivefold in the untrained man, and by as much as eightfold in the elite athlete. Increasing venous return is a critical but much overlooked component of the physiological response to exercise. Cardiac disorders such as constrictive pericarditis, restrictive cardiomyopathy and pulmonary hypertension are recognised to impair preload and cause exercise limitation; however, the effects of peripheral venous obstruction on cardiac function have not been well described. This manuscript will discuss how obstruction of the iliocaval venous outflow can lead to impairment in exercise tolerance, how such obstructions may be diagnosed, the potential implications of chronic obstructions on sympathetic nervous system activation, and relevance of venous compression syndromes in heart failure with preserved ejection fraction.

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

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.