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Biomedical subjects

M Pourcyrous

Publications and source records attributed to M Pourcyrous.

26 records · Page 2Linked to original sources

Brain superoxide anion generation during asphyxia and reventilation in newborn pigs.

Superoxide anion generation during severe asphyxia and reventilation was assessed in newborn pigs. Using closed cranial windows over the parietal cortices, superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined during asphyxia/reventilation. Asphyxia was induced by turning off the respirator and occluding the endotracheal tube. In each animal, 2.4 mM NBT dissolved in artificial cerebrospinal fluid was placed under one window and under the opposite window, NBT (2.4 mM) plus SOD (60 U/mL) dissolved in artificial cerebrospinal fluid was used. A significant increase in SOD-inhibitable NBT reduction was observed in asphyxiated piglets (14.67 +/- 4.5 pmol/mm2 x 20 min) when compared with control piglets (2.82 +/- 1.1 pmol/mm2 x 20 min). In another group in which the animals were treated with indomethacin (5 mg/kg i.v.) before asphyxia/reventilation, there was minimal SOD-inhibitable NBT reduction. Our results indicate that superoxide anion is generated on the cerebral cortex during asphyxia/reventilation via the prostaglandin endoperoxide synthase pathway.

Animals↗

Indomethacin reduces the risks of severe intraventricular hemorrhage.

A prospective, random selection, double-blind clinical trial was carried out to determine the efficacy of indomethacin in preventing periventricular-intraventricular hemorrhage (PV-IVH). Babies who were born in our institution, had birth weights less than or equal to 1500 gm, and had no PV-IVH or grade 1 PV-IVH were given either placebo (n = 70) or indomethacin (n = 71), 0.2 mg/kg intravenously at 6 hours of age and 0.1 mg/kg at 18 and 30 hours. Two major outcomes were determined: the development of grades 2 to 4 PV-IVH and the development of severe PV-IVH (i.e., hemorrhages with blood filling greater than 50% of the ventricles and in some cases with associated parenchymal echodensities). Grades 2 to 4 PV-IVH occurred in 16 (23%) of the indomethacin group and 27 (39%) of the placebo group (p less than 0.03). The incidence of severe PV-IVH was 3% in the indomethacin-treated babies and 14% in the control group (p less than 0.02). The influence of other perinatal factors on the incidence of grades 2 to 4 or severe PV-IVH was determined by stepwise logistic regression. Placebo use, early grade 1 PV-IVH, lower birth weight, and higher fraction of inspired oxygen at 6 hours of life were associated with higher estimated odds of the development of grades 2 to 4 PV-IVH. Placebo use, male gender, lower 5-minute Apgar score, and a large base deficit were predictive of severe PV-IVH. Estimated odds ratios of severe PV-IVH with placebo use and male gender were 11.25:1 and 9:1, respectively. Thus indomethacin prophylaxis reduced the relative risk of grades 2 to 4 PV-IVH and severe PV-IVH, but other perinatal variables contributed significantly to the overall risk of PV-IVH.

Apgar Score↗

Acetylcholine dramatically increases prostanoid synthesis in piglet parietal cortex.

We investigated effects of exogenous acetylcholine on prostanoid synthesis by parietal cortex in neonatal pigs. Cerebrospinal fluid (CSF) with no drug, and CSF containing acetylcholine at 10(-6) to 10(-3) M was injected under a 'closed' cranial window, and after 5 min the CSF was collected and analyzed by radioimmunoassay for prostaglandin (PG) E2, PGF2 alpha, PGD2, 6-keto-PGF1 alpha (the hydrolysis product of prostacyclin), and thromboxane (TX) B2 (the hydrolysis product of TXA2). PGE2 and PGF2 alpha were the predominant prostanoids in CSF under control conditions. Levels of all CSF prostanoids increased after topical application of acetylcholine, with the largest increases being for PGE2 and PGF2 alpha. During control conditions, levels were 1294 +/- 170 (mean +/- S.E.M.) pg/ml for PGE2 (n = 16), 1032 +/- 143 pg/ml for PGF2 alpha (n = 3), 659 +/- 92 pg/ml for 6-keto-PGF1 alpha (n = 15), 141 +/- 44 pg/ml for TXB2 (n = 12), and were below detectable levels for PGD2. Following application of 10(-3) M acetylcholine, levels were 34,535 +/- 5438 pg/ml for PGE2, 15,539 +/- 2772 pg/ml for PGF2 alpha, 2967 +/- 547 pg/ml for 6-keto-PGF1 alpha, 580 +/- 105 pg/ml for TXB2, and 556 +/- 221 pg/ml for PGD2. These results suggest that prostanoids could play a role in mediating effects of acetylcholine in the brain, or in modulating acetylcholine release via a negative feedback mechanism.

Acetylcholine↗

Hyperthermia increases cerebral metabolic rate and blood flow in neonatal pigs.

We examined effects of hyperthermia on cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) in anesthetized, newborn pigs (2-5 days old). CBF and CMRO2 were measured during normothermia (38 degrees C) and during hyperthermia induced by body heating (42 degrees C). During normothermia, total CBF was 32 +/- 3 ml.min-1.100 g-1 (n = 9), and CMRO2 was 1.34 +/- 0.08 ml O2.100 g-1.min-1 (n = 7). During hyperthermia, total CBF increased by 97 +/- 23% and CMRO2 by 65 +/- 24%. We also examined whether cerebral resistance vessels were responsive under these conditions. During hyperthermia, total CBF was 63 +/- 6 ml.min-1.100 g-1, and CMRO2 was 2.13 +/- 0.27 ml O2.100 g-1.min-1. During sustained hyperthermia, intravenous injection of 5 mg/kg of indomethacin decreased total CBF by 45 +/- 7% (n = 9), and CMRO2 fell by 55 +/- 10% (n = 5). We conclude that 1) hyperthermia increases CBF and CMRO2, and 2) the dilated cerebrovascular bed during hyperthermia still is responsive to a constrictor stimulus.

Animals↗

Platelet activating factor: a potent constrictor of cerebral arterioles in newborn pigs.

This study characterized the nature of the response to platelet activating factor (PAF) in the cerebral microcirculation of the newborn pig. Pial arterioles were observed directly using a closed cranial window in chloralose-anesthetized piglets. Topical application of 10-100 ng/ml PAF produced dose-dependent decreases in pial arteriolar diameter; diameters were 193 +/- 27 microns for control, 167 +/- 25 microns at 10 ng/ml, and 129 +/- 21 microns at 100 ng/ml. Topical application of 30-300 ng/ml norepinephrine and 3-30 ng/ml U46619, a purported thromboxane A2 receptor agonist, also produced dose-dependent decreases in pial arteriolar diameter. After topical administration of U66985 (1 microgram/ml), a putative PAF antagonist, responses to PAF were attenuated significantly, but responses to norepinephrine and U46619 were unchanged. Moreover, intravenously administered U66985 (0.1 mg/kg) antagonized PAF responses as well. Responses to PAF were unchanged after cyclooxygenase and leukotriene receptor inhibition. Further, PAF did not increase cortical subarachnoid cerebrospinal fluid prostaglandin or leukotriene levels. These data indicate that PAF is a potent constrictor of cerebral arterioles in newborn pigs and that its mechanism of action is independent of formation of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. These data also suggest that U66985 may be a selective PAF antagonist that crosses the blood-brain barrier. Since PAF is an endogenous lipid released from a variety of tissues and may be an important mediator of inflammation and allergic reaction, PAF could be involved in the pathophysiology of the cerebral circulation in the perinatal period.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Postasphyxial increases in prostanoids in cerebrospinal fluid of piglets.

The dilator stimuli that contribute to postasphyxial increases in cerebral blood flow in the neonate are unclear. To assess the possible role of cyclooxygenase products in these responses, we measured pial arteriolar diameter in six piglets and determined levels of prostaglandin (PG) E2 and 6-keto-PG F1 alpha (hydrolysis product of PGI2) in cerebrospinal fluid (CSF) bathing the parietal cortex during control conditions, after 4-10 min of complete respiratory arrest (asphyxia), and after 5-12 min of reventilation. Pial arterioles are important resistance vessels in the cerebral circulation. Baseline pial arteriolar diameter was 220 +/- 40 micron (mean +/- SEM) and increased to a maximum of 252 +/- 49 and 267 +/- 56 micron after asphyxia and reventilation, respectively. During control conditions, CSF PGE2 (n = 6) and 6-keto-PGF1 alpha (n = 4) levels were 1947 +/- 310 and 794 +/- 147 pg/ml, respectively. During asphyxia, CSF levels of PGE2 did not increase, whereas 6-keto-PGF1 alpha increased modestly. During reventilation, CSF PGE2 increased to 3576 +/- 499 pg/ml, and 6-keto-PGF1 alpha increased to 2846 +/- 123 pg/ml. In other experiments, we determined that these CSF levels of PGE2 and PGI2 (as 6-keto-PGF1 alpha) were within the vasodilator range for pial arterioles. We conclude that postasphyxial increases in pial arteriolar diameter are associated with a rise in CSF levels of dilator prostanoids.

Animals↗

Indwelling umbilical arterial catheter: a preferred sampling site for blood culture.

Indwelling umbilical arterial catheter was evaluated prospectively as an alternative site for blood culture sampling. In 282 infants, 318 paired blood cultures were obtained from the peripheral vein and from the indwelling umbilical arterial line. Duration of umbilical catheter placement ranged from 0.5 to 196 hours; in 17% of the infants, catheters were in place for between 24 and 196 hours. In 13 blood culture pairs the same pathogens were found and had been obtained from the peripheral vein and the umbilical arterial line. Two pairs were positive for discrepant organisms. A total of 11 pairs were positive in one site only, with five positive from peripheral vein only and the other six from the umbilical arterial catheter. However, most of these single-site positive blood cultures were apparently true positives based on supporting laboratory data for infection. Contamination rates were 1.3% and 0.9% for peripheral vein and umbilical arterial catheter blood cultures, respectively. Thus, in sick neonates, the indwelling umbilical arterial line was an alternative and perhaps a preferred site for blood culture sampling.

Blood↗

Overestimation of neonatal PO2 by collection of arterial blood gas values with the butterfly infusion set.

The butterfly, or scalp vein infusion set, is a widely used and convenient way to collect arterial blood gas samples in neonates. Analyzing arterial blood gas values by using this technique in a clinical situation, we obtained elevated values of PO2 in blood samples collected and measured from butterfly tubing in comparison with tuberculin syringe controls. Diffusion of gas through the polyvinylchloride tubing was suggested and proved by a study of pairs of butterfly and tuberculin syringes filled with venous blood from the blood bank. In conclusion, the butterfly gives falsely elevated PO2 values as a result of gas diffusion and is not a reliable technique for arterial blood gas sampling in neonates.

Blood Specimen Collection↗