Infusion Of PGE1 Research Articles

PDA Stenting for Ductal-Dependent Pulmonary Blood Flow: Management of Prostaglandin E1 Infusion.

Newborns with ductal-dependent pulmonary blood flow require PGE1 infusion prior to ductal stenting to ensure patency of the PDA. There is no consensus, however, on management of PGE in the peri-procedural period in terms of timing of discontinuation of the drug. This review will focus on the rationale for continuing or discontinuing PGE, a brief review of some of the published recommendations, and will make some final recommendations regarding PGE management. Reasons to continue PGE include ensuring the patient is stable and has adequate oxygenation prior to the stenting procedure. In addition, continuation of PGE makes the procedure logistically easier since the timing for the intervention is not dependent upon ductal constriction. The rationale for discontinuation of PGE is to ensure there is adequate ductal constriction to securely place a stent and minimize the risk of stent embolization. Decision-making regarding the discontinuation of PGE must be individualized and is primarily dependent upon PDA morphology.

Effect of intra-uterine infusion of prostaglandin E1 on equine serum level and intra-ovulatory interval

Prostaglandin E2 (PGE2) has important roles in the transport of early equine embryos, pregnancy maintenance and treatment of uterotubal obstruction. There is a lack of information on PGE absorption from the uterus. We hypothesized that circulating levels of PGE metabolite (PGEM) would increase ten minutes after uterine infusion of PGE1 on day (D)10 and 12 post-ovulation and frequent treatment would affect the intra-ovulatory interval (IOI). Our objective was to compare the effect of treatment and D post-ovulation on serum PGEM. A randomized study with n=4 or 5 mares per group was performed. Mares were examined using transrectal ultrasound to detect estrus, ovulation (D0) and their IOI. A pre infusion jugular blood sample was obtained using plain vacuum tubes and the perineum was washed. Prostaglandin E1 (2 mg in dimethylsulfoxide) (DMSO) or DMSO alone was loaded into a 0.5mL sterile insemination straw and placed in an embryo transfer gun. Mares were sedated using xylazine 0.4 mg/kg IV, a vaginal speculum was introduced, and PGE1 or DMSO was infused transcervically into the uterus every 6 hours for 4 treatments on either D10 or D12. Following infusion, the uterus was briefly massaged per rectum and a post treatment blood sample was obtained 10 minutes later. There was a rest estrous cycle in between studyperiods. Serum was separated and stored at -20°C. PGEM was measured in pre and post samples using commercial enzyme-linked immunosorbent assays (ELISA) (Cayman Chemical) validated in our laboratory, according to the manufacturer's instructions. The assays had intra- and inter-assay CVs of 7.3 and 11%. Data were evaluated for normality. Statistical analyses were performed using StatPlus v8 using Kruskal-Wallis tests at P<.05 to compare the overall median Post – Pre PGEM level of the 4 time points. The median Post-Pre PGEM pmol/L(quartiles) were: D10 DMSO -10.9 (-21.5, -1.6); D10 PGE1 2920.7 (1774.5, 3990.8), DMSO D12 -13.8 (-22.8, -3.7); PGE1 D12 703.5 (677.2, 1510.5). The median IOI days (quartiles) were: D10 DMSO 25.5 (24.5, 26.5); D10 PGE1 23 (21.5, 24.3); D12 DMSO 22 (21.3, 22); D12 PGE1 22.5 (20.8, 23.2). Post – Pre median PGEM level was greater in PGE1 than DMSO treated mares on D10 (P =.021) and D12 (P =.021). On D10 16/16, and D12 12/16 infusions of PGE1 resulted in a >2fold increase in PGEM within 10 minutes. There was no effect of treatment on IOI, and no effect of D post-ovulation on PGEM. There is rapid absorption of PGE1 from the uterus, however at the dose and frequency used in this study there was no apparent effect on luteal function.

Ivemark syndrome with obstructed supracardiac TAPVC- case report

Heterotaxy disorder is a disturbance in the usual left and right distribution of the thoracic and abdominal organs. Ivemark syndrome is one such heterotaxy disorder. It is a rare disorder which affects males more than females with majority of cases presenting in the neonatal period mainly due to complex congenital cardiac disease. Here is a case report of rare disorder of the neonate with Ivemark syndrome with obstructed supracardiac total anomalous pulmonary venous connection (TAPVC). Management of obstructed supracardiac TAPVC is complicated as PGE1 infusion is contraindicated and immediate surgical correction is advised.

Lessons from prenatal diagnosis and in utero transfer of fetuses with transposition of the great arteries

Prenatal diagnosis of transposition of the great arteries (TGA) reduces neonatal mortality and morbidity. The mortality of prenatally diagnosed TGA remains scarcely described. To review the experience of prenatal diagnosis and in utero transfer of fetuses with TGA to assess the limits of this program and to describe outcomes of prenatally diagnosed TGA. From 1999 to 2017, we reviewed all cases of prenatally diagnosed TGA born at our institution. Files were analyzed for discordances between prenatal and postnatal diagnosis, status at birth, neonatal management, and outcomes. In total, 748 fetuses with TGA (470 simple, 278 complex) were delivered at our institution. Discordance between pre- and postnatal diagnosis was noted in 14.8% with two third having consequence on surgical treatment. Median term was 39 WG. The proportion of premature delivery (< 37WG) was 5.3%, the majority being late-preterm (> 34 WG). Fourteen percent were intubated in the delivery room and 1.7% required resuscitation maneuvers. Sixty-four percent had a Rashkind procedure that was done in 15% of cases in the delivery room. Fifty-five percent received PGE1 infusion and 38% had a Rashkind and PGE1 infusion. There were 9 deaths before surgery (1.2%) with two not related to the TGA. A fourth experienced neonatal complications including mainly respiratory distress requiring ventilation, infection, necrotizing enterocolitis, pulmonary hypertension and iatrogenic events. Surgical mortality was 1.8% (4 simple TGA and 10 complex). Seven additional deaths occurred during the first year follow-up, 6 being related to late cardiac complications. Overall survival at one year was 96%. Prenatal diagnosis and in utero transfer of fetuses with TGA does not eliminate the risk of preoperative mortality. The proportion of immediate distress is high and the need for intensive care in the delivery room is frequent. Finally, preoperative mortality accounts for a third of the one-year mortality in this population.

Abstract P-327: OUTCOMES OF BABIES WITH CONGENITAL DIAPHRAGMATIC HERNIA IN A NON ECMO PEADIATRIC INTENSIVE CARE UNIT IN SOUTH AUSTRALIA. A RETROSPECTIVE OBSERVATIONAL STUDY OVER 16 YEARS.

Aims & Objectives: Introduction: Congenital diaphragmatic hernia (CDH) is a common birth defect which is associated with high morbidity and mortality. The cause for mortality is usually severe persistent pulmonary hypertension (PPHN) resulting from pulmonary hypoplasia. With Advances in intensive care and ECMO, mortality has reduced to < 20% in many centres. We report outcomes from Non ECMO tertiary PICU.1,2,3 Methods This retrospective observational study done over 16 years in a tertiary PICU without ECMO in South Australia. Results 62 babies born or referred to us with CDH had survival rate of 87%comparable to many ECMO centres. We noted severe PPHN in 30% (19/62) managed with inhaled Nitric oxide (iNO) of whom 36%(7/62) expired. Prostaglandin infusion was given to avoid right heart failure in 27 %(17/62) of which 50% received nitric and Prostaglandin infusion (8/62). Conclusions The outcome of CDH has improved with survival rates of 70–90% in centres even without ECMO. We report a survival rate of 87% with conventional management NO and PGE1 infusion. PGE1 results in ductal patency with reduction of right ventricular strain to manage transitional PPHN. We report increasing use of PGE1 over the past decade with improved outcomes.

Restoring Fetal Circulation as a Means of Bridging Treatment Prior to Surgical Repair of Anomalous Origin of the Right Pulmonary Artery from the Ascending Aorta with Persistent Pulmonary Hypertension of the Newborn.

Anomalous origin of one pulmonary artery from the ascending aorta is a rare congenital anomaly. Even more rarely reported is its presence in conjunction with persistent pulmonary hypertension of the newborn (PPHN). We present a case of a full-term infant, initially thought to have PPHN and later found to have anomalous origin of the right pulmonary artery from the ascending aorta. We discuss our management concept which included use of PgE1 infusion to restore fetal circulation prior to surgical treatment in this unique clinical scenario.

Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α.

In ruminants, uterine pulses of prostaglandin (PG) F2α characterize luteolysis, while increased PGE2/PGE1 distinguish early pregnancy. This study evaluated intrauterine (IU) infusions of PGF2α and PGE1 pulses on corpus luteum (CL) function and gene expression. Cows on day 10 of estrous cycle received 4 IU infusions (every 6 h; n=5/treatment) of saline, PGE1 (2 mg PGE1), PGF2α (0.25 mg PGF2α), or PGE1+PGF2α. A luteal biopsy was collected at 30 min after third infusion for determination of gene expression by RNA-Seq. As expected, IU pulses of PGF2α decreased (P<0.01) P4 luteal volume. However, there were no differences in circulating P4 or luteal volume between saline, PGE1, and PGE1+PGF2α, indicating inhibition of PGF2α-induced luteolysis by IU pulses of PGE1. After third pulse of PGF2α, luteal expression of 955 genes were altered (false discovery rate [FDR]<0.01), representing both typical and novel luteolytic transcriptomic changes. Surprisingly, after third pulse of PGE1 or PGE1+PGF2α, there were no significant changes in luteal gene expression (FDR>0.10) compared to saline cows. Increased circulating concentrations of the metabolite of PGF2α (PGFM; after PGF2α and PGE1+PGF2α) and the metabolite PGE (PGEM; after PGE1 and PGE1+PGF2α) demonstrated that PGF2α and PGE1 are entering bloodstream after IU infusions. Thus, IU pulses of PGF2α and PGE1 allow determination of changes in luteal gene expression that could be relevant to understanding luteolysis and pregnancy. Unexpectedly, by third pulse of PGE1, there is complete blockade of either PGF2α transport to the CL or PGF2α action by PGE1 resulting in complete inhibition of transcriptomic changes following IU PGF2α pulses.

Pharmacokinetic Analysis of Continuous Intravenous Infusion of Lipo-Prostaglandin E1 As a Prophylaxis of Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation

Introduction: Prostaglandin E1 (PEG1) has various pharmacological effects such as vasodilation, inhibition of platelet aggregation, inhibition of superoxide anion generation, activation of the fibrinolytic system and inhibition of vascular smooth muscle cell proliferation. Continuous intravenous infusion of PGE1 as a prophylaxis of hepatic veno-occlusive disease (VOD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) have previously been shown to be effective. Further study has been done with continuous intravenous infusion of lipo-prostaglandin E1 (lipo-PGE1) because it can be used in smaller doses to avoid toxicities since it is a form of PGE1 dissolved in the lipid emulsion of soybean oil and thus has greater and long lasting effects. However, it has not been evaluated pharmacokinetically.Methods: We performed a prospective explorative pharmacokinetic study on patients who received continuous intravenous infusion of lipo-PGE1 at a dose of 1mcg/kg/day as a prophylaxis of VOD during HSCT at Seoul National University Children's Hospital. Eligible patients were those at high risk of developing VOD (previous abdominal irradiation, liver function abnormality, busulfan or total body irradiation based conditioning, age under 18 years old) but who cannot use low dose heparin due to low platelet count, bleeding tendency or allergy. Dose of lipo-PGE1 could be increased to 1.5mcg/kg/day if patients showed clinical symptoms of VOD, before the establishment of VOD diagnosis. Lipo-PGE1 level was measured before the start of infusion (B level), between 1 hour and 72 hours after the start of infusion (P1 level), and after neutrophil engraftment (P2 level). Additional samplings were done if the dose of infusion was changed or if the condition of the patient changed significantly. Patients were evaluated for the occurrence and severity of VOD. VOD was diagnosed without limitation of onset time, when patients had 2 or more of the following features: serum total bilirubin of greater than 2 mg/dL, hepatomegaly or right upper quadrant pain of liver origin, or unexplained weight gain of greater than 2% over baseline.Results: Thirty patients were enrolled between January 2015 and May 2016 and all of them were eligible for analysis. Patients underwent HSCT at median age of 12.2 years old for hematologic malignancies, solid tumors, brain tumors, and non-malignant diseases. Donors and stem cell sources were variable. Twenty patients received busulfan-based conditioning and 1 patient received total body irradiation based conditioning. Continuous intravenous infusion of lipo-PGE1 was started at median 1 day before the start of the conditioning regimen and was administered for a median duration of 29 days (range, 23-56 days). Dose of lipo-PGE1 was adjusted to 1.5mcg/kg/day in 2 patients at median 18 days (range, 14-21 days) from start of continuous infusion due to increasing serum total bilirubin or tender hepatomegaly. B level and P1 level were measured in all enrolled patients and P2 level was measured in all 28 of the patients who achieved neutrophil engraftment. The P1 level was 6.60 ± 2.88 (mean ± standard deviation) pg/mL and the clearance was 308.48 ± 233.04 L/h. The P2 level was significantly lower than P1 level at 5.55 ± 2.06 pg/mL (P=0.005) and the clearance was greater at 392.64 ± 302.78 L/h but it was not statistically significant (P=0.109). The coefficient of variability (CV%) of lipo-PGE1 level and clearance were 43.64% and 75.54% respectively at P1 and 37.12% and 77.11% respectively at P2. Between-subject variability of lipo-PGE1 level and clearance (11.18 and 51.65 %) were higher than intra-subject variability (7.19 and 7.40 %). No significant relationship was found between the level or clearance of lipo-PGE1 and occurrence or severity of VOD. VOD developed in 2 patients (6.7%) but both resolved completely with antithrombin-III based treatment at median 38 days from diagnosis. There was no adverse event or death related to lipo-PGE1 prophylaxis and there were no deaths related to VOD.Conclusions: We herein provide the first prospective explorative pharmacokinetic data of continuous infusion of lipo-PGE1 as a prophylaxis of VOD in patients undergoing HSCT. We also suggest that lipo-PGE1 is efficient and safe as a prophylaxis of VOD in patients undergoing HSCT. DisclosuresNo relevant conflicts of interest to declare.

Congenital Heart Disease Requiring Maintenance of Ductus Arteriosus in Critically Ill Newborns Admitted at a Tertiary Neonatal Intensive Care Unit.

Congenital heart diseases (CHD) have been reported to be responsible for 30 to 50% of infant mortality caused by congenital disabilities. In critical cases, survival of newborns with CHD depends on the patency of the ductus arteriosus (PDA), for maintaining the systemic or pulmonary circulation. The aim of the study was to assess the efficacy and side effects of PGE (prostaglandin E) administration in newborns with critical congenital heart disease requiring maintenance of the ductus arteriosus. All clinical and paraclinical data of 66 infants admitted to one referral tertiary level academic center and treated with Alprostadil were analyzed. Patients were divided into three groups: Group 1: PDA dependent pulmonary circulation (n=11) Group 2: PDA dependent systemic circulation (n=31) Group 3: PDA depending mixed circulation (n=24). The mean age of starting PGE1 treatment was 2.06 days, 1.91 (+/-1.44) days for PDA depending pulmonary flow, 2.39 (+/-1.62) days for PDA depending systemic flow and 1.71 (+/1.12) for PDA depending mixing circulation. PEG1 initiation was commenced 48 hours after admission for 72%, between 48-72 hours for 6%, and after 72 to 120 hours for 21% of newborns detected with PDA dependent circulation. Before PEG1 initiation the mean initial SpO2 was 77.89 (+/- 9.2)% and mean initial oxygen pressure (PaO2) was 26.96(+/-6.45) mmHg. At the point when stable wide open PDA was achieved their mean SpO2increased to 89.73 (+/-8.4)%, and PaO2 rose to 49 (+/-7.2) mmHg. During PGE1 treatment, eleven infants (16.7%) had apnea attacks, five children (7.5%) had convulsions, 33 (50%) had fever, 47 (71.2%) had leukocytosis, 52 (78.8%) had edema, 25.8% had gastrointestinal intolerance, 45.5% had hypokalemia, and 63.6% had irritability. For those infants with severe cyanosis or shock caused by PDA dependent heart lesions, the initiation and maintenance of PGE1 infusion is imperative. The side effects of this beneficial therapy were transient and treatable.

Neonatal management and outcomes of prenatally diagnosed CHDs.

The aim of this study was to determine the probability of intervention at birth after prenatal diagnosis of CHD. A 10-year retrospective study including all foetuses with a prenatally diagnosed CHD and those delivered in a tertiary-care cardiac centre between January, 2002 and December, 2011 was carried out. Patients were classified into eight groups according to the anticipated risk of neonatal intervention. The need for urgent intervention and/or PGE1 infusion within the first 48 hours of life was 47% (n=507/1080): 72% (n=248) for CHD at risk for a Rashkind procedure, 77% (n=72) for CHD with ductal-dependent pulmonary flow, 13% (n=22) for CHD with potentially ductal-dependent pulmonary flow, 94% (n=62) for CHD with ductal-dependent systemic flow, 29% (n=88) for CHD with potentially ductal-dependant systemic flow, 50% (n=4) for total anomalous pulmonary venous connection, and 17% (n=1) for CHD with atrio-ventricular block. In all, 34% of the patients received PGE1 infusion and 21.4% underwent urgent catheter-based or surgical interventions; 10% of patients without anticipated risk (n=10) underwent an early intervention; 6.7% (n=73) of the patients died; and 55% (n=589) had an intervention before discharge from hospital. Half of the neonates with foetal CHD benefited from an urgent intervention or PGE1 infusion at birth. We recommend scheduled delivery and in utero transfer for transposition of the great arteries, double-outlet right ventricle with sub-pulmonary ventricular septal defect, total anomalous pulmonary venous connection, CHD with atrio-ventricular block with heart rate <50, all ductal-dependant lesions, and CHD with potentially ductal-dependant systemic flow.

(901) - Mid-term Outcomes After Transplantation Following Resuscitative Bilateral Pulmonary Artery Banding in High-Risk Single Ventricle Neonates and Infants: Single Center Experience

Bilateral pulmonary artery banding (bPAB) ± ductal stenting (DS) has been performed at our institution as a resuscitative intervention for patients considered too high risk (profound metabolic acidosis, ventricular dysfunction, significant AVV regurgitation, and/or end-organ dysfunction) for conventional single ventricle (SV) palliation. Mid-term outcomes in those undergoing transplantation (TXPLT) using this strategy were analyzed. Retrospective review of all SV patients <3 months who underwent bPAB and DS or maintenance of ductal patency by PGE1 between January 2007 and October 2011 and survived to discharge. Echocardiographic, angiographic, operative and clinical data were reviewed. Follow-up was complete in 100%. Fifteen of 24 (62.5%) patients s/p bPAB at a median age of 9 days (2-39d), gestational age of 38-weeks (36-41wk), and weight of 3.2 kg (2.7-4.1kg) survived to hospital discharge. Maintenance of ductal patency was by DS (N=8) or PGE1 infusion (N=7). Median follow-up for the cohort was 53 months. Cardiac diagnoses included hypoplastic left heart syndrome (HLHS)/variant HLHS in 12 and unbalanced AVC in 3. In the HLHS group, 7/12 (58.3%) had an intact or highly restrictive atrial septum requiring either open (N=1) or transcatheter atrial septostomy (N=6) ± atrial stent placement (N=3). Conventional Norwood (NW, N=7) or comprehensive stage 2 (CS2, N=1) was performed in patients suitable for surgical palliation (recovery of ventricular function) while TXPLT was undertaken in 7 deemed unsuitable (persistent ventricular dysfunction ± severe AVVR). Pulmonary artery intervention occurred in 10 (66.6%) patients---4 at TXPLT, 1 s/p TXPLT, 1 at NW, 4 s/p subsequent surgical palliation. All survived to hospital discharge. Six of 7 (85.7%) s/p NW underwent BDG, 3 underwent Fontan and 2 await Fontan completion. Late deaths occurred in 1 patient s/p TXPLT and 3 s/p surgical palliation (1 s/p NW, 1 s/p BDG, 1 s/p CS2). Six of 7 (85.7%) transplanted patients are alive at median follow-up of 57 months. Mid-term outcomes after TXPLT following initial resuscitative bPAB in high-risk single ventricle neonates and infants are excellent. Pulmonary artery intervention either at the time of or after surgical palliation or TXPLT is common.

Abstract 301: Testosterone propionate in Ischemia-reperfusion (I/R) induced Acute Kidney Injury (AKI)

Acute kidney injury (AKI) is a leading cause of morbidity and mortality, and men are more prone to AKI than women implicating androgens as a causative factor whereas estrogens have been thought to be protective. These effects are independent of both androgen and estrogen receptors. We showed recently that infusion of testosterone 3 hrs post reperfusion protected rats from renal injury following ischemia/reperfusion (I/R). In the present study, we tested the hypothesis that testosterone works as a renal vasodilator perhaps by increasing nitric oxide. Male SD rats (8-14 wks; n=3-5/grp) were subjected to sham surgery or I/R induced AKI with bilateral clamping of renal vessels for 30 min. Three hrs after reperfusion, rats were given testosterone propionate (20 μg/kg iv over 10 min) or vehicle (0.75%EtOH). Rats were placed in metabolism cages for 24hrs for nitrate/nitrite excretion (UNOxV), and euthanized and blood taken for creatinine (PCr). I/R increased PCr and decreased UNOxV, compared to shams (0.58±0.05 vs. 3.99±0.36 mg/dL, p&lt;0.0001; UNOxV: 8.54±1.7 vs 1.7±0.78 μmol/day/kg BW, p&lt;0.001). Testosterone attenuated the increase in PCr (2.03±0.23 mg/dL, p&lt; 0.01) but had no effect on UNOxV (3.79±0.91 μmol/day/kg). Pretreatment of rats with L-NAME (1mg/kg/day; dose that did not increase BP) for 48 hours prior to I/R abolished the improvement in PCr with testosterone (PCr: 3.73±0.82 mg/dL, p&lt;0.05 vs no LNAME). Infusion of renal vasodilator PGE2 (30μg/kg iv over 10 min 3 hrs after reperfusion) attenuated PCr compared to I/R alone (2.95±0.21mg/dL, p&lt;0.01) but was independent of increased NO (2.61±0.63 μmol/day/kg, p=NS vs I/R alone), and was not as effective in reducing PCr as testosterone (p&lt;0.05). These data show that low dose testosterone infusion 3 hrs post reperfusion improves renal function in AKI perhaps by causing renal vasodilation. When NO synthesis is blocked, testosterone is incapable of improving PCr after I/R. Furthermore, although the known renal vasodilator PGE2 also improves PCr in I/R, although not as effectively as testosterone. These data continue to support the notion that testosterone infusion has therapeutic potential for the treatment of I/R induced AKI in humans. Supported by NIH R01HL66072, P01HL05971 and AHA 14POST18640015.

Abstract 170: Aspirin Reduces Mortality Caused by Intracranial Aneurysm Rupture in mPGES-1 Deficient Mice

Inflammation plays an important role in formation and rupture of intracranial aneurysms. Prostaglandin (PG) E2, a by-product of microsomal prostaglandin E2 synthase (mPGES)-1, is associated with inflammation and cerebrovascular dysfunction. We hypothesized that mPGES-1 deficiency protects against rupture of intracranial aneurysms. Intracranial aneurysms were induced in mPGES-1 knockout (KO) and wild-type (WT) mice with DOCA-salt hypertension and an intracranial injection of elastase. Systolic blood pressure and water intake (1% saline) was similar in WT and mPGES-1 KO mice. All WT mice survived 3 weeks after surgery and did not develop signs of subarachnoid hemorrhage (SAH). The majority of WT mice [73% (8/11)] developed aneurysmal dilatations in the cerebral arteries without evidence of SAH. In contrast, half of mPGES-1 deficient mice died or showed signs of SAH during follow-up (P&lt;0.05). Postmortem analysis showed SAH in 56% (9/16) of mPGES-1 deficient mice. Unruptured aneurysms with no evidence of SAH were found in 25% (4/16) of mPGES-1 deficient mice. Subcutaneous infusion of PGE2 (1 mg/kg/d) to mPGES-1 KO mice did not appear to attenuate mortality or intracranial aneurysm rupture (p&gt;0.05). Another group of mPGES-1 KO mice were treated with aspirin (6 mg/kg/d) or vehicle (water) by gavage since day 2 after surgery. Mortality caused by symptomatic aneurysm rupture was significantly reduced in aspirin (25% (3/12) vs vehicle (58% (7/12)) treated mPGES-1 KO mice (P&lt;0.05). In conclusion, we found that genetic deficiency of mPGES-1 is associated with increased aneurysm rupture (p&lt;0.01) and mortality (p&lt;0.05) in a mouse model of intracranial aneurysms. Aspirin treatment significantly reduced mortality in mPGES-1 KO mice (P&lt;0.05). Therefore, mPGES-1 and aspirin appear to play a protective role against rupture of intracranial aneurysms in mice.

Therapeutic manipulation of the ductus arteriosus: current options and future prospects

The ductus arteriosus is a large fetal vessel connecting the pulmonary artery with the aorta and allowing right ventricular blood to bypass the unexpanded lungs. At birth, with the start of lung ventilation and the attendant rise in blood oxygen tension, the ductus closes and the cardiovascular system acquires its final arrangement. However, in the prematurely born infant, this shunt may remain patent (patent ductus arteriosus--PDA) with adverse consequences on hemodynamic homeostasis. Conversely, there are cardiac malformations in which patency of the duct is required to maintain the pulmonary or systemic circulation prior to corrective surgery. Based on the notion that patency is an active process sustained primarily by prostaglandin (PG) E₂, PDA is currently managed with synthesis inhibitors, indomethacin or ibuprofen, while any necessary persistence of the duct after birth is achieved with the infusion of PGE₁. However, the former procedure presents a relatively high incidence of failures for the likely combination of the 2 events: the relaxing influence of the agents compensating for the loss of PGE₂ and the immaturity of the oxygen‑triggered contractile mechanism. On the other hand, PGE₁ treatment loses some of its efficacy with time and may also be complicated by troublesome side effects. This article presents possible new approaches to therapy still based on the manipulation of the relaxing mechanism(s) responsible for duct patency. At the same time, however, the idea is put forward that the management of these sick infants may find its definitive solution only with tools being designed on the operation of the oxygen‑sensing/effector system.

Long-Term Recurrence-Free Survival After Liver Transplantation from an ABO-Incompatible Living Donor for Treatment of Hepatocellular Carcinoma Exceeding Milano Criteria in a Patient With Hepatitis B Virus Cirrhosis: A Case Report

The early results of liver transplantations (OLT) in patients with advanced hepatocellular carcinoma (HCC) were poor because of frequent tumor recurrence. However, OLT has significant, theoretical advantage that it removes both the tumor and the organ that is at a risk of malignancy. The Japanese law on organ transplantation limited the availability of cadaveric liver donors until its revision on July 17, 2011. ABO-incompatible OLT was formerly contraindicated because performed anti-A/B antibodies on recipient endothelial cells raised the risk of antibody-mediated humoral graft rejection. We have herein described four successful cases of steroid withdrawal among adult patients who underwent living donor OLT from ABO-incompatible donors. In addition, we transplanted a liver from a living donor into an ABO-incompatible recipient on August 9, 2004. The 55-year-old man with HCC due to hepatitis B virus (HBV) a cirrhosis had a Child-Pugh score of C, and Model for End-stage Liver Disease score of 22. Two tumors greater than 5 cm, exceeded the Milan criteria. His des-gamma-carboxy prothrombin level was 6 mAu/mL, and alpha-fetoprotein, 18.78 ng/mL. Antirejection therapy included multiple perioperative plasmaphereses and splenectomy; with an immunosuppressive regimen consisting of tacrolimus, methylprednisolone, and mycophenolate mofetil. The maintenance dose of immunosuppression did not differ from that of ABO-identical cases. After transplantation, we used intrahepatic arterial infusion therapy with prostaglandin E1 (PG E1). The patient had complications of portal vein thrombosis, hepatic artery thrombosis, and acute myocardial infarction, which were treated by interventional radiology in the posttransplantation period. We controlled the HBsAb titer by administering hepatitis B immunoglobulin and lamivudine (200 IU/L doses) for 1 year after OLT and 100 IU/L doses thereafter. As a result, the patient achieved long-term, disease-free graft survival without steroids. He currently has good liver function and leads a normal lifestyle. Our results suggested the feasibility of controlling antibody-mediated humoral rejection and other complications in living donor liver transplantations into ABO-incompatible adults via intrahepatic arterial PG E1 infusion splenectomy, and plasmapheresis with regular immunosuppression. Withdrawal of steroids, HBV vaccination, and lamivudine, an nucleoside analog reverse transcriptase inhibitor, have achieved long-term (7 years) survival without recurrent HBV infection or tumor.

Intra-Arterial Prostaglandin E1Infusion in Patients with Rest Pain: Short-Term Results

Purpose. To present our results after short-term (1 month) intra-arterial infusion therapy of PGE1-alprostadil via a port system implanted in the ipsilateral external iliac artery (EIA) in patients with severe rest pain. Methods. Ten patients with severe rest pain were included. All patients showed extensive peripheral vascular disease below the knee. The tip of the catheter was introduced via a retrograde puncture in the ipsilateral external iliac artery (EIA). The patients received intraarterial infusion of PGE1, 20 mgr alprostadil daily, via the port catheter for 1 month. Results. Clinical success was evaluated according to subjective grading of pain (group A significant decrease, group B moderate decrease and group C no response). A significant decrease of rest pain was observed in 8 (group A, 80%) patients, a moderate decrease in 2 (Group B, 20%), whereas no patients demonstrated any significant response. Both patients of group B had Buergers' disease and continue to smoke during therapy. No peripheral thrombosis or clinical deterioration was noticed. Conclusion. Intraarterial infusion of PGE1 alprostadil on a daily basis, using a port catheter into the ipsilateral EIA, in selected patients with severe rest pain, seems to be very effective, without any serious complications.

Reimplantation of Anomalous Single Coronary Artery From Pulmonary Artery: Diagnosis and Surgical Management

A newborn presented in cardiogenic shock with the diagnosis of anomalous single coronary artery from pulmonary artery and was successfully revived with prostaglandin (PGE1) infusion. She underwent surgical implantation of her coronary arteries while receiving PGE1 infusion to maintain high oxygen tension for the coronaries during cardiopulmonary bypass. She was discharged in 2 weeks with good biventricular function and moderate mitral regurgitation. At 2 months follow-up, she was gaining weight with preserved ventricular function and moderate mitral regurgitation.

In vivo intra-luteal implants of prostaglandin (PG) E 1 or E 2 (PGE 1, PGE 2) prevent luteolysis in cows. II: mRNA for PGF 2α, EP1, EP2, EP3 (A–D), EP3A, EP3B, EP3C, EP3D, and EP4 prostanoid receptors in luteal tissue

Previously, it was reported that chronic intra-uterine infusion of PGE 1 or PGE 2 every 4 h inhibited luteolysis in ewes by altering luteal mRNA for luteinizing hormone (LH) receptors and unoccupied and occupied luteal LH receptors. However, estradiol-17β or PGE 2 given intra-uterine every 8 h did not inhibit luteolysis in cows, but infusion of estradiol + PGE 2 inhibited luteolysis. In contrast, intra-luteal implants containing PGE 1 or PGE 2 in Angus or Brahman cows also inhibited the decline in circulating progesterone, mRNA for LH receptors, and loss of unoccupied and occupied receptors for LH to prevent luteolysis. The objective of this experiment was to determine how intra-luteal implants of PGE 1 or PGE 2 alter mRNA for prostanoid receptors and how this could influence luteolysis in Brahman or Angus cows. On day-13 Angus cows received no intra-luteal implant and corpora lutea were retrieved or Angus and Brahman cows received intra-luteal silastic implants containing Vehicle, PGE 1, or PGE 2 and corpora lutea were retrieved on day-19. Corpora lutea slices were analyzed for mRNA for prostanoid receptors (FP, EP1, EP2, EP3 (A–D), EP3A, EP3B, EP3C, EP3D, and EP4) by RT-PCR. Day-13 Angus cow luteal tissue served as pre-luteolytic controls. mRNA for FP receptors decreased in day-19 Vehicle controls compared to day-13 Vehicle controls regardless of breed. PGE 1 and PGE 2 up-regulated FP gene expression on day-19 compared to day-19 Vehicle controls regardless of breed. EP1 mRNA was not altered by any treatment. PGE 1 and PGE 2 down-regulated EP2 and EP4 mRNA compared to day-19 Vehicle controls regardless of breed. PGE 1 or PGE 2 up-regulated mRNA EP3B receptor subtype compared to day-19 Vehicle control cows regardless of breed. The similarities in relative gene expression profiles induced by PGE 1 and PGE 2 support their agonistic effects. We conclude that both PGE 1 and PGE 2 may prevent luteolysis by altering expression of mRNA for prostanoid receptors, which is correlated with changes in luteal mRNA for LH receptors reported previously in these same cows to prevent luteolysis.

Balloon atrial septostomy: The oldest cardiac interventional procedure in Mansoura

Abstract Background Balloon atrial septostomy (BAS) was first described by Rashkind and Miller in 1966 and remains an important interventional procedure in the palliation of certain forms of congenital heart disease (CHD). Creating an atrial septa1 defect in patients with transposition of the great arteries (d-TGA) will enhance bidirectional mixing of the pulmonary and systemic venous blood, hence improving oxygen saturation. The aim of the work is to review and report our experience using balloon atrial septostomy in different CHD. Method We retrospectively reviewed the hospital records, echocardiographic and cardiac catheterization reports of patients subjected for BAS during the period from January 2001 till January 2010. One hundred and ninety two patients with CHD (78.5% d-TGA, 10% mitral atresia, 7.5% tricuspid atresia, and 4% hypoplastic left heart syndrome) underwent BAS. Their gestational age was 38.63 ± 1.48 weeks, postnatal age (median 3.5 days, range 1–54) and weight 3.08 ± 0.37 kg, 57.5% was male and 42.5% was female. All patients received PGE1 infusion before the procedure to maintain the ductal patency in a dose of 0.05–0.1 μg/kg/min. Results One hundred twenty two procedures (63.5%) were done in neonatal intensive care at bedside and 70 procedures (36.5%) in the catheterization laboratory. General anesthesia was used in 31.3% of patients whereas conscious sedation was used in 68.7% of patients. Femoral access in 78% while umbilical access in 22%. Seven F sheath was used in 100% of case. The Miller catheter was used in 75% and a Z-5 septostomy catheter in 25% of cases. The diameter of the atrial communication increased from 2.75 ± 0.97 mm to 7.07 ± 0.79 mm (p Conclusion BAS is safe and an effective palliative procedure for different CHD with good immediate results in our institution.

In vivo intra-luteal implants of prostaglandin (PG) E 1 or E 2 (PGE 1, PGE 2) prevent luteolysis in cows. I. Luteal weight, circulating progesterone, mRNA for luteal luteinizing hormone (LH) receptor, and occupied and unoccupied luteal receptors for LH

Previously, it was reported that chronic intra-uterine infusion of PGE 1 or PGE 2 every four hours inhibited luteolysis in ewes. However, estradiol-17β or PGE 2 given intra-uterine every 8 h did not inhibit luteolysis in heifers, but infusion of estradiol + PGE 2 inhibited luteolysis in heifers. The objective of this experiment was to determine whether and how intra-luteal implants containing PGE 1 or PGE 2 prevent luteolysis in Angus or Brahman cows. On day-13 post-estrus, Angus cows received no intra-luteal implant and corpora lutea were retrieved or Angus and Brahman cows received intra-luteal silastic implants containing Vehicle, PGE 1, or PGE 2 and corpora lutea were retrieved on day-19. Coccygeal blood was collected daily for analysis for progesterone. Breed did not influence the effect of PGE 1 or PGE 2 on luteal mRNA for LH receptors or unoccupied or occupied luteal LH receptors did not differ ( P > 0.05) so the data were pooled. Luteal weights of Vehicle-treated Angus or Brahman cows from days-13–19 were lower ( P < 0.05) than those treated with intra-luteal implants containing PGE 1 or PGE 2. Day-13 Angus luteal weights were heavier ( P < 0.05) than Vehicle-treated Angus cows on day-19 and luteal weights of day-13 corpora lutea were similar ( P > 0.05) to Angus cows on day-19 treated with intra-luteal implants containing PGE 1 or PGE 2. Profiles of circulating progesterone in Angus or Brahman cows treated with intra-luteal implants containing PGE 1 or PGE 2 differed ( P < 0.05) from controls, but profiles of progesterone did not differ ( P > 0.05) between breeds or between cows treated with intra-luteal implants containing PGE 1 or PGE 2. Intra-luteal implants containing PGE 1 or PGE 2 prevented ( P < 0.05) loss of luteal mRNA for LH receptors and unoccupied or occupied receptors for LH compared to controls. It is concluded that PGE 1 or PGE 2 alone delays luteolysis regardless of breed. We also conclude that either PGE 1 or PGE 2 prevented luteolysis in cows by up-regulating expression of mRNA for LH receptors and by preventing loss of unoccupied and occupied LH receptors in luteal tissue.