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Biomedical subjects

D H Penning

Publications and source records attributed to D H Penning.

33 records · Page 2Linked to original sources
PubMed1996

Magnesium sulfate adversely affects fetal lamb survival and blocks fetal cerebral blood flow response during maternal hemorrhage.

Magnesium sulfate is commonly used in high-risk pregnancies, even though its actions in the fetus during maternal/fetal stress are not completely understood. The present study tested the hypothesis that magnesium sulfate alters the fetal cerebral blood flow response to hypoxemia produced during maternal hemorrhage. It was conducted in instrumented near-term fetal lambs at 123 days of gestation. Experimental treatment involved four periods of maternal hemorrhage over a 60-min period during fetal infusion of 0.25 g (n = 5) or 0.30 g (n = 6) magnesium sulfate, or normal saline (n = 11). The level of fetal cerx500l blood flow was determined using radiolabeled microspheres. For all three treatment groups, maternal hemorrhage produced fetal hypoxemia and some fetal demise. During fetal infusion of saline, 1 of 11 (9%) of the fetuses died; with the 0.25-g magnesium sulfate regimen, 1 of 5 (20%) died; and with the 0.30-g magnesium sulfate regimen, 3 of 6 (50%) of the fetuses died. Magnesium sulfate caused an increase in the proportion of fetal death produced by maternal hemorrhage (P < 0.05). Among surviving fetuses, hemorrhage-induced hypoxemia increased fetal cerebral blood flow during saline infusion. In contrast, infusion of magnesium sulfate had an inhibitory effect on this compensatory increase in fetal cerebral blood flow (P = 0.003). These data indicate that, in the sheep, magnesium sulfate increases fetal mortality and inhibits the compensatory increase in fetal cerebral blood flow during maternal hemorrhage-induced fetal hypoxemia.

Animals↗
PubMed1995

Effect of exposure in vitro to ethanol and hypoxia on gamma-aminobutyric acid efflux in the hippocampus of the fetal and adult guinea-pig.

The objective of this study was to determine the effects of acute direct exposure to ethanol, hypoxia or ethanol plus hypoxia on K+-stimulated gamma-aminobutyric acid (GABA) efflux (neuronal release minus uptake) in the hippocampus of the near-term fetal and adult guinea-pig. Transverse hippocampal slices were studied in a static-interface system. Exposure in vitro to ethanol or hypoxia involved 10-min incubation with 50 mM ethanol or 10-min incubation in a 95% N2/5% CO2 environment. GABA was quantitated by HPLC. Ethanol did not alter K+-stimulated GABA efflux; hypoxia augmented K+-stimulated GABA efflux three-fold in the near-term fetus and seven-fold in the adult; concurrent exposure to ethanol did not alter the effect of hypoxia. The data demonstrate that, for acute direct exposure to hypoxia and/or ethanol, only hypoxia increases K+-stimulated GABA efflux, the magnitude of which is dependent on the extent of development of the GABA system.

Animals↗
PubMed1995

An evaluation of the effect of anesthetic technique on reproductive success after laparoscopic pronuclear stage transfer. Propofol/nitrous oxide versus isoflurane/nitrous oxide.

BACKGROUND: Laparoscopic pronuclear stage transfer (PROST) is the preferred method of embryo transfer after in vitro fertilization in many infertility programs. There are scant data to recommend the use or avoidance of any particular anesthetic agent for use in women undergoing this procedure. The authors hypothesized that propofol would be an ideal anesthetic for laparoscopic PROST because of its characteristic favorable recovery profile that includes minimal sedation and a low incidence of postoperative nausea and vomiting. The purpose of the study was to compare propofol and isoflurance with respect to postanesthetic recovery and pregnancy outcomes after laparoscopic PROST. METHODS: One hundred twelve women scheduled for laparoscopic PROST were randomized to receive either propofol/nitrous oxide or isoflurane/nitrous oxide for maintenance of anesthesia. RESULTS: Visual analog scale scores for sedation were lower in the propofol group than in the isoflurance group at all measurements between 30 min and 3 h after surgery. More women experienced emesis and were given an antiemetic during recovery in the isoflurance group than in the propofol group. However, the percentage of pregnancies with evidence of fetal cardiac activity was 54% in the isoflurane group compared with only 30% in the propofol group (P = 0.023). Also, the ongoing pregnancy rate was greater in the isoflurane group than in the propofol group (54% vs. 29%, P = 0.014). CONCLUSIONS: Propofol/nitrous oxide anesthesia was associated with lower clinical and ongoing pregnancy rates compared with isoflurane/nitrous oxide anesthesia.

Adult↗
PubMed1995

Glutamate release from the ovine fetal brain during maternal hemorrhage. A study using chronic in utero cerebral microdialysis.

BACKGROUND: Glutamate has been implicated in the pathophysiology of neuronal injury associated with cerebral hypoxia-ischemia. A model using chronic in utero microdialysis was developed to sample the extracellular space of the fetal brain. Using this model, we tested the hypothesis that glutamate efflux from the parasagittal parietal cortex of near-term fetuses would increase during maternal hemorrhage. METHODS: Twelve near-term fetal sheep were instrumented with vascular catheters, and a microdialysis probe(s) was implanted into the parasagittal parietal cortex. After a 3-day recovery period, the animals were subjected to maternal hemorrhage until either the fetal pH was < 7.00 or the fetus died. The extracellular glutamate concentration in the collected dialysate was determined by high pressure liquid chromatography (HPLC). RESULTS: Maternal hemorrhage resulted in an 80-90% decrease in uterine blood flow, a decrease fetal po2, and a mixed metabolic and respiratory fetal acidosis. There were two groups of fetuses, survivors (n = 5) and nonsurvivors (n = 7). The nonsurvivor group showed a large increase (10-30-fold) in peak glutamate release (P = 0.0015). Survivors demonstrated a small (threefold) increase that was not statistically significant (P = 0.065), unless one animal with very low probe recovery was excluded (P = 0.0048). CONCLUSIONS: Extracellular glutamate release from the fetal brain can occur during maternal hemorrhage with fetal acidemia. The pathophysiologic role (if any) of glutamate release in the survivors remains to be elucidated. Our results are consistent with the hypothesis that in utero release of glutamate occurs during periods of fetal asphyxia. This experimental preparation of chronic fetal brain microdialysis can be used to monitor the brain extracellular concentration of any dialyzable substance in response to stress, including maternal hemorrhage.

Animals↗
PubMed1995

Dose-dependent effects of acute in vivo ethanol exposure on extracellular glutamate concentration in the cerebral cortex of the near-term fetal sheep.

The cerebral cortex is a target site of ethanol teratogenesis. L-Glutamate is a major excitatory neurotransmitter that plays an important neurotrophic role in brain development. It has been proposed that optimal function of the glutamate neuronal system is required for normal brain development; overactivation could lead to excitotoxic-induced neuronal injury, whereas underactivation could delay/restrict brain development. The objective of this study was to test the hypothesis that acute in vivo ethanol exposure alters basal glutamate release in the fetal cerebral cortex. The experimental approach involved measuring fetal cortical extracellular glutamate concentration using the technique of in vivo microdialysis. Near-term fetal sheep were chronically instrumented with a microdialysis probe placed in the parasagittal cortex. At 124 +/- 3 days of gestation, the effects of maternal intravenous infusion of 2 g or 4 g ethanol/kg maternal body weight or an equivalent volume of saline, given as four equally divided doses over 5 hr, on fetal cerebral cortical extracellular glutamate concentration were determined. None of the three treatment regimens produced fetal or maternal demise during the time course of the study. There was an ethanol dose-dependent increase, p = 0.005, in extracellular glutamate concentration in the fetal cerebral cortex. This increase was paroxysmal in nature and was not directly related to the fetal blood ethanol concentration. In view of the proposed role for glutamate in neuronal development, this apparent ethanol-induced increase in glutamate release may be important in the pathogenesis of ethanol teratogenesis involving the cerebral cortex.

Alcohol Drinking↗
PubMed1994

Neuropathology of the near-term and midgestation ovine fetal brain after sustained in utero hypoxemia.

OBJECTIVE: The neuropathologic mechanisms of the ovine fetal brain in response to several hours of sustained hypoxemia with variable degrees of metabolic acidemia was investigated in both the preterm and near-term ovine fetus. STUDY DESIGN: Three groups of fetuses were studied in each of the near-term and midgestation groups: a hypoxic group, a control group, and an uninstrumented control group. Histopathologic studies were performed after a 40-hour recovery period after experimentation. RESULTS: Pathologic findings consisted of predominately white matter damage with some adjacent cortical necrosis but no selective neuronal injury. In the near-term group the hypoxia group fetuses demonstrated significantly higher white matter injury scores than did control group fetuses (p < 0.05). Periventricular white matter injury was the predominant pattern seen in the midgestation group. CONCLUSIONS: In spite of normalization of biophysical and biochemical parameters after hypoxemia both midgestation and near-term fetuses sustained pathologic changes. Presence or extent of injury did not correlate with the degree of hypoxemia or metabolic acidosis achieved.

Acidosis↗
PubMed1994

Does early administration of epidural analgesia affect obstetric outcome in nulliparous women who are in spontaneous labor?

BACKGROUND: Some studies suggest that epidural analgesia prolongs labor and increases the incidence of cesarean section, especially if it is administered before 5 cm cervical dilation. The purpose of the current study was to determine whether early administration of epidural analgesia affects obstetric outcome in nulliparous women who are in spontaneous labor. METHODS: Informed consent was obtained from 344 healthy nulliparous women with a singleton fetus in a vertex presentation, who requested epidural analgesia during spontaneous labor at at least 36 weeks' gestation. Each patient was randomized to receive either early or late epidural analgesia. Randomization occurred only after the following conditions were met: (1) the patient requested pain relief at that moment, (2) a lumbar epidural catheter had been placed, and (3) the cervix was at least 3 cm but less than 5 cm dilated. Patients in the early group immediately received epidural bupivacaine analgesia. Patients in the late group received 10 mg nalbuphine intravenously. Late-group patients did not receive epidural analgesia until they achieved a cervical dilation of at least 5 cm or until at least 1 h had elapsed after a second dose of nalbuphine. Ten of the 344 patients were excluded because of a protocol violation or voluntary withdrawal from the study. RESULTS: Early administration of epidural analgesia did not increase the incidence of oxytocin augmentation, prolong the interval between randomization and the diagnosis of complete cervical dilation, or increase the incidence of malposition of the vertex at delivery. Also, early administration of epidural analgesia did not result in an increased incidence of cesarean section or instrumental vaginal delivery. Seventeen (10%) of 172 women in the early group and 13 (8%) of 162 women in the late group underwent cesarean section (relative risk for the early group 1.22; 95% confidence interval 0.62-2.40). Patients in the early group had lower pain scores between 30 and 150 min after randomization. Infants in the late group had lower umbilical arterial and venous blood pH and higher umbilical venous blood carbon dioxide tension measurements at delivery. CONCLUSIONS: Early administration of epidural analgesia did not prolong labor, increase the incidence of oxytocin augmentation, or increase the incidence of operative delivery, when compared with intravenous nalbuphine followed by late administration of epidural analgesia, in nulliparous women who were in spontaneous labor at term.

Adult↗
PubMed1993

Effect of hypoxia on glutamate efflux and synaptic transmission in the guinea pig hippocampus.

Simultaneous assessment of synaptic activity and glutamate efflux in guinea pig hippocampal brain slices was made before, during and after a 10-min period of hypoxia. Spontaneous glutamate efflux was assessed by determining glutamate concentration in the superfusion medium at discrete times using high performance liquid chromatography (HPLC). Synaptic activity was assessed using extracellular recording of the evoked population spike in the CA1 region following stimulation of the Schaffer collateral pathway. Hypoxia decreased (P < 0.05) the amplitude of the population spike by 3 min and abolished it by 5 min. This was accompanied by an increase (P < 0.05) in glutamate concentration in the superfusate at 10 min. Following re oxygenation, the population spike returned to baseline amplitude by 5 min and was greater (P < 0.05) than baseline at 10 and 20 min of recovery. Glutamate concentration returned to baseline levels by 1 min of recovery. This experimental preparation can be used to explore the temporal relationship between glutamate efflux and synaptic activity during hypoxia. The results of this study indicate that, in the hippocampal CA1 region, post-synaptic elements are more sensitive than their presynaptic counterparts to hypoxia.

Animals↗
PubMed1993

Obstetrical analgesia in a parturient with antithrombin III deficiency.

Antithrombin III (AT III) deficiency is a rare inherited disorder which predisposes patients to thrombotic complications. Anticoagulation is necessary to prevent recurrent thrombosis and high doses of heparin are often required. Anticoagulation complicates analgesia in parturients with the condition. We describe such a patient, in pre-term labour, who was successfully managed during labour with intravenous nalbuphine and inhaled nitrous oxide (N2O).

Administration, Inhalation↗
PubMed1992

Yohimbine-precipitated clonidine withdrawal: an experimental model of the antihypertensive drug withdrawal syndrome.

In this study, a model of the clonidine withdrawal syndrome in normotensive rats was used to investigate the mechanisms and sites of the cardiovascular responses associated with this withdrawal. Clonidine (400 micrograms.kg-1.day-1), an alpha 2-adrenergic receptor agonist, was administered to rats via indwelling osmotic minipumps for 7 days. Withdrawal was precipitated by an intravenous injection of the alpha 2-adrenergic receptor antagonist yohimbine under alpha-chloralose anaesthesia, and the blood pressure and heart rate responses were recorded. Yohimbine (0.25, 0.50, and 1.0 mg/kg i.v.) in clonidine-treated rats provoked an immediate rise in blood pressure and heart rate. Similar injections in saline-treated rats produced slight hypotension and modestly increased the heart rate. Intracerebroventricular (i.c.v.) yohimbine injection (30 or 120 micrograms/kg in 10 microL volume) failed to elicit signs of withdrawal in clonidine-treated animals, but a subsequent intravenous injection of yohimbine (0.5 mg/kg) provoked brisk signs of withdrawal. hexamethonium (2 mg/kg) pretreatment did not abolish the increase in the heart rate, but it delayed the blood pressure increase. Pretreatment with atropine sulfate (1 mg/kg) did not block the yohimbine-induced increase in heart rate or blood pressure. This study demonstrates that yohimbine can effectively produce cardiovascular signs of withdrawal in rats chronically exposed to clonidine. The lack of i.c.v. yohimbine suggests that the antagonist-precipitated withdrawal may not have a central origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Release of glutamate and gamma-aminobutyric acid in the ovine fetal hippocampus: ontogeny and effect of hypoxia.

The effects of increased potassium ion concentration (50 mM) and hypoxia on the efflux of glutamate and gamma-aminobutyric acid (GABA) were studied in ovine fetal hippocampal slices using the static-pool-interface superfusion method at three selected gestational ages (85 days, 105 days, 135 days; term, about 147 days). There was no difference in spontaneous efflux of either amino acid across the three gestational ages. Potassium ion stimulated the efflux of glutamate in the hippocampus of the 85-days-old fetus only, and this efflux of glutamate was not calcium-ion dependent. Potassium ion stimulated the efflux of GABA in the ovine fetal hippocampus at days 85 and 105 only; this efflux was calcium-ion dependent. A ten-minute period of hypoxia did not enhance the efflux of either glutamate or GABA. The data indicate that both glutamate and GABA are present in the ovine fetal hippocampus, and can be released by depolarizing concentrations of potassium ion in the immature fetus. The lack of potassium ion-evoked efflux of glutamate and GABA in the mature fetal hippocampus may reflect a toxic response to this stimulus. The lack of calcium ion regulation of glutamate efflux compared with GABA efflux indicates either a difference in maturation of glutamatergic synaptic mechanisms compared with GABAergic mechanisms, or is indicative of glial release of glutamate. Prolonged, severe hypoxia (greater than 10 min) may be required to evoke efflux of glutamate in the developing fetal hippocampus.

Animals↗
PubMedDate not supplied

Ethanol increases uterine blood flow and fetal arterial blood oxygen tension in the near-term pregnant ewe.

Fetal hypoxia is a hypothesized mechanism of ethanol teratogenesis. The objective of this study was to test this hypothesis by determining the effects of maternal ethanol infusion on uterine blood flow (UBF) and fetal oxygen status. UBF was measured with an electromagnetic flow probe placed around the left maternal uterine artery of the surgically recovered instrumented near-term pregnant sheep at 124 +/- 3 days of gestation (term = 147 days). Experimental treatment involved maternal infusion of 2 g (n = 3) or 4 g (n = 5) ethanol/kg maternal body weight, or 0.9% saline (n = 4) over a 5-h period. Arterial blood samples were collected at regular intervals to monitor maternal ethanol concentration and fetal PO2. Maternal ethanol infusion produced a dose-dependent increase (p = 0.0009) in UBF. Ethanol infusion also increased (p = 0.03) fetal arterial PO2. Overall, these findings indicate that fetal hypoxia is not a mechanism of ethanol teratogenesis.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Bolus maternal cocaine administration does not produce a large increase in fetal sheep cerebral cortical glutamate concentration.

Human cocaine use during pregnancy may result in postnatal neurologic dysfunction and abnormal behavior. L-Glutamate, the major excitatory neurotransmitter in the brain, plays an important role in cerebral cortical development. An optimal level of glutamate is required for normal neuronal development. We tested whether acute cocaine exposure produces large increases in glutamate release in the intact cerebral cortex of the near-term fetal sheep. Cocaine 3.0 mg kg(-1) IV bolus produced the expected increase in maternal and fetal mean arterial pressure, increase in fetal heart rate, decrease in uterine blood flow, and decrease in fetal arterial blood pO2 (N = 5). The percentage increases in extracellular glutamate concentration in the fetal cerebral cortex measured by in utero microdialysis were 7%, 15%, 17%, 17%, and 43% in each fetus (upper 95% confidence bound for the median = 43%). We conclude that if cocaine increases glutamate concentration in the developing cerebral cortex, the increase in magnitude is small relative to the changes produced by other interventions such as ethanol or umbilical cord occlusion. Mechanisms other than increases in cerebral cortical glutamate concentration probably contribute to the neurologic injury associated with prenatal cocaine exposure.

Animals↗