Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies

Objective: A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type currents). It is speculated that those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as human umbilical vein (HUV). Having in mind its crucial role in the proper fetal oxygenation the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions - gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Materials and methods: Healthy, diabetic and hypertensive pregnancies were subjects of this investigation. Each group was consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 pregnancies with PIH. After pharmacology analysis, immunohistochemistry and Western blot were performed. Results: Immunohistochemistry revealed similar expression pattern of both, Kv4.2 and Kv4.3 subunits, in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with immunohistochemical staining. The expression of Kv4.2 and Kv4.3 subunits was not significantly different between the groups. Conclusion: Collectively, this is the first study that demonstrated presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during the course of GDM and PIH. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. Also, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment.

Breath of Life: Heart Disease Link to Developmental Hypoxia

Heart disease remains one of the greatest killers. In addition to genetics and traditional lifestyle risk factors, we now understand that adverse conditions during pregnancy can also increase susceptibility to cardiovascular disease in the offspring. Therefore, the mechanisms by which this occurs and possible preventative therapies are of significant contemporary interest to the cardiovascular community. A common suboptimal pregnancy condition is a sustained reduction in fetal oxygenation. Chronic fetal hypoxia results from any pregnancy with increased placental vascular resistance, such as in preeclampsia, placental infection, or maternal obesity. Chronic fetal hypoxia may also arise during pregnancy at high altitude or because of maternal respiratory disease. This article reviews the short- and long-term effects of hypoxia on the fetal cardiovascular system, and the importance of chronic fetal hypoxia in triggering a developmental origin of future heart disease in the adult progeny. The work summarizes evidence derived from human studies as well as from rodent, avian, and ovine models. There is a focus on the discovery of the molecular link between prenatal hypoxia, oxidative stress, and increased cardiovascular risk in adult offspring. Discussion of mitochondria-targeted antioxidant therapy offers potential targets for clinical intervention in human pregnancy complicated by chronic fetal hypoxia.

Intravenous isotonic fluid challenge, and L-arginine infusion for oligoamnios and diminished fetal movements: a preliminary study

Background: Utero-placental insufficiency is one of the major causes of oligoamnios and diminished fetal movements (FM). Rapid intravenous isotonic fluid infusion within the cardiovascular reserve improves tissue perfusion in all systems. We tested the hypothesis that isotonic fluid challenge may improve uteroplacental perfusion, which may, in turn improve fetal oxygenation, liquor formation, and FM.Methods: In this descriptive study, twenty-three antenatal mothers with gestational age >26 weeks, and with amniotic fluid index (AFI) <8 cm were included. Intravenous isotonic fluid challenge with 2 or 3 pints of ringer’s lactate, at the rate of 180-200 drops/minute, twice daily for 2-3days and, L-arginine infusion, 300 ml/day alternate days for 2-3 doses were given. Women were advised to take more than 3 litres of water a day. AFI was recorded once daily for 5 days, and then biweekly. The fluid challenge was repeated whenever AFI diminished <8.00 cm. AFI and perceived FM were graded. Pregnancies were terminated when there was no response to fluid challenge. The trend of changes in AFI and FM grades, number of days pregnancies continued, and perinatal outcomes were recorded.Results: We noted recurrent fall in AFI after an initial arise in 20 women, which required recurrent fluid challenges. Pregnancies could be continued for 18±8.5 days (median±SD). Three women, with case of absent FM, reported FM within 1 hour after initiation of the fluid challenge. There were no perinatal deaths.Conclusions: Intravenous isotonic fluid challenge and L-arginine infusion, improves AFI and FM, and helps to prolong pregnancies towards viability.

A DOUBLE BLIND COMPARATIVE STUDY BETWEEN INTRATHECAL BUPIVACAINE AND INTRATHECAL FENTANYLAS THE INITIAL DOSE OF COMBINED SPINAL EPIDURAL TECHNIQUE FOR LABOUR ANALGESIA

Introduction: Labour pain is among the most severe pain a woman can experience in her lifetime. Painful labour has decrimental effects on both mother and fetus leads to severe physical and psychological stress. Maternal hyperventilation in response to pain reduces fetal oxygenation and hypoventilation between contractions combined with decreased blood ow worsens fetal hypoxemia. It has been suggested that conning women to bed during labour may cause the labour to be longer and more painful with increase in abnormal presentation, instrumental deliveries and fetal distress. Aims And Objectives:The onset, quality and duration of their analgesic action. Incidence of unwanted effects like muscle weakness, hypotension, pruritus, nausea/vomiting, fetal bradycardia by the individual drugs. Materials And Methods: The study was conducted in the department of anesthesia, Darbhanga Medical College & Hospital, Laheriasarai, Bihar. Methods of collection of data (including sampling procedure if any) : After institutional committee approval and written informed consent from parturients and their relatives for the procedure the study was conducted and data were collected. Results: Duration of analgesia was found varying widely. It was 55±12.34 minutes in Group I whereas 75 ±14.36 minutes in Group II. The incidence of pruritus almost mild or negligible in both groups. The incidence of motor weakness in group II was 24 (80%) whereas in group I it was 10(33%). There was signicant statistics difference in motor weakness between two groups (p< 0.001) by Chi square test 9 with yate's correction. Other side effects differences between two groups were not statistically signicant. Summary And Conclusion:Both the drugs provided excellent quality of analgesia to the parturient in pain. The difference in duration of analgesia was signicant between the two groups statistically. Mean duration of analgesia lasted for 55 minutes in group I whereas in group II, it lasted for 75 minutes. Main side effects encountered in this study were motor weakness of longer duration in group II than in group I. Other side effects like nausea-vomiting were comparable to each other and were minimal in nature.

Neonatal lamb mortality: major risk factors and the potential ameliorative role of melatonin

High incidences of pre-weaning mortality continue to limit global sheep production, constituting a major economic and welfare concern. Despite significant advances in genetics, nutrition, and management, the proportion of lamb deaths has remained stable at 15–20% over the past four decades. There is mounting evidence that melatonin can improve outcomes in compromised ovine pregnancies via enhanced uterine bloodflow and neonatal neuroprotection. This review provides an overview of the major risk factors and underlying mechanisms involved in perinatal lamb mortality and discusses the potential of melatonin treatment as a remedial strategy. Supplementing pregnant ewes with melatonin enhances uterine bloodflow and fetal oxygenation, and potentially birthweight and neonatal thermogenic capacity. Melatonin freely crosses the ovine placenta and blood-brain barrier and provides neuroprotection to the fetal lamb during periods of chronic and acute hypoxia throughout gestation, with improved behavioural outcomes in hypoxic neonates. The current literature provides strong evidence that maternal melatonin treatment improves outcomes for lambs which experience compromised in utero development or prolonged parturition, though to date this has not been investigated in livestock production systems. As such there is a clear basis for continued research into the effects of maternal melatonin supplementation during gestation on pre-weaning survival under extensive production conditions.