dinoprost and Asphyxia

The premature infant is at increased risk of cerebral white matter injury. Melatonin is neuroprotective in adult models of focal cerebral ischemia and attenuates ibotenate-induced white matter cysts in neonatal mice. Clinically, melatonin has been used to treat sleep disorders in children without major side effects. The aim of this study was to investigate the protective and anti-inflammatory effects of melatonin in the immature brain following intrauterine asphyxia. Fetal sheep at 90 d of gestation were subjected to umbilical cord occlusion. Melatonin (20 mg/kg, n = 9) or vehicle (n = 10) was administered IV to the fetus, starting 10 min after the start of reperfusion and continued for 6 h. Melatonin treatment resulted in a slower recovery of fetal blood pressure following umbilical cord occlusion, but without changes in fetal heart rate, acid base status or mortality. The production of 8-isoprostanes following umbilical cord occlusion was attenuated and there was a reduction in the number of activated microglia cells and TUNEL-positive cells in melatonin treated fetuses, suggesting a protective effect of melatonin. In conclusion, this study shows that melatonin attenuates cell death in the fetal brain in association with a reduced inflammatory response in the blood and the brain following intrauterine asphyxia in mid-gestation fetal sheep.

Topics: Animals; Anti-Inflammatory Agents; Asphyxia; Blood Gas Analysis; Blood Pressure; Brain; Cell Death; Dinoprost; Female; Fetal Diseases; Gestational Age; Heart Rate, Fetal; Humans; Infant, Newborn; Leukomalacia, Periventricular; Melatonin; Neuroprotective Agents; Pregnancy; Sheep; Sulfhydryl Compounds; Time Factors; Umbilical Cord

Free radicals have been implicated in the development of injury to the immature retina. Asphyxia increases free radicals as well as prostaglandins (PG) in neural tissues. We assessed whether in the retina the cyclooxygenase pathway contributes to free radical formation after oxidative insults such as asphyxia, which in turn disrupts retinal function. Newborn pigs were treated with either saline, ibuprofen (194 mumol/kg i.v.), or allopurinol (1 mmol/kg i.v.), and retinal malondialdehyde (MDA), hydroperoxides, PGE2 and PGF2 alpha levels, and the amplitudes and implicit times of the a- and b-waves of the full-field electroretinogram were measured before and 1 h after a 5-min period of asphyxia. In saline-treated animals, asphyxia caused a marked increase (p < 0.01) in MDA, hydroperoxides, PGE2, and PGF2 alpha concentrations in the retina. This was associated with a significant decrease (p < 0.01) in the b-wave amplitude measured under scotopic and photopic conditions and an increase in the b-wave implicit times. Ibuprofen and another cyclooxygenase inhibitor, indomethacin (28 mumol/kg i.v.), decreased PGE2 and PGF2 alpha levels and prevented the increase in MDA and hydroperoxides after asphyxia. Allopurinol maintained low concentrations of MDA and hydroperoxides after asphyxia. Both ibuprofen and allopurinol prevented the postasphyxial changes in the b-wave amplitude and diminished the delay in implicit time observed after asphyxia in saline-treated pigs. Our findings suggest that in the retina after asphyxia free radicals appear to originate primarily from the cyclooxygenase pathway and contribute to the deterioration in retinal electrophysiologic function of the newborn animal. Cyclooxygenase inhibitors, like free radical scavengers, may protect retinal function from deteriorating after oxidative stresses.

Topics: Allopurinol; Animals; Animals, Newborn; Asphyxia; Dinoprost; Dinoprostone; Electroretinography; Free Radicals; Ibuprofen; Lipid Peroxides; Malondialdehyde; Retina; Swine

The effects of exogenously applied prostaglandin F2 alpha (PGF2 alpha) and prostacyclin (PGI2) on asphyxic anoxia was studied in curarized and artificially ventilated cats. Anoxia was induced by stopping the ventilation and checking the changes in the EcoG. Cortical resistance (CRs) was evaluated as time between stopping the ventilation and the extinction of ECoG. Cortical recovery (CRc) was expressed as time between restitution of ventilation and reappearance of brain activity. Anoxia resistance index (ARI) was defined as the ratio between these two parameters (CRs/CRc). PGF2 alpha was applied by 5 minute i.v. and intracarotid (i.c.) infusion in a dose of 10 micrograms/kg/min, and PGI2 in a dose of 250 ng/kg/min for 15 minutes intracarotidly. The results show that both the i.c. and i.v. infusion with PGF2 alpha led to a significant decrease of CRs and prolongation of CRc resulting in decrease of ARI. The changes are more expressed at i.v. infusion, PGI2 does not improve the ECoG changes evoked by hypoxia. Suggestions for the possible mechanism of PGF2 alpha action and for the failure of PGI2 to protect the brain are made.

Topics: Animals; Asphyxia; Cats; Dinoprost; Electroencephalography; Epoprostenol; Female; Hypoxia; Male; Prostaglandins; Prostaglandins F