naloxone and Fetal-Hypoxia

Objectives were to identify and to evaluate controlled trials of interventions for term infants developing hypoxic-ischaemic encephalopathy. Five randomized trials concerning prophylactic anticonvulsant therapy for neonatal HIE were identified. There were methodological problems with all of them, and meta-analysis of barbiturate prophylaxis showed no significant effect on death or disability. One randomized trial of allopurinol showed short-term benfits, but was too small to test death or disability. One small randomized trial of hypothermia found no adverse effects, but was too small to examine death or disability. No adequate trials of dexamethasone, calcium channel blockers, magnesium sulphate, or naloxone have yet been completed, but pilot studies in infants have shown the risks of magnesium sulphate and calcium channel blockers.

Topics: Allopurinol; Anti-Inflammatory Agents; Anticonvulsants; Asphyxia Neonatorum; Calcium Channel Blockers; Dexamethasone; Diuretics, Osmotic; Fetal Hypoxia; Free Radical Scavengers; Humans; Hypothermia, Induced; Infant, Newborn; Magnesium Sulfate; Mannitol; Naloxone; Perinatal Care; Research Design; Treatment Outcome

The interaction between the plasma catecholamine response to hypoxemia and endogenous opiate receptor blockade was investigated in 9 fetal lambs. The animals were randomly assigned to receive either normal saline (control group 1) or two doses of naloxone (group 2 = 0.5 mg/kg; group 3 = 1.0 mg/kg) by bolus injection followed by continuous infusion. Arterial PO2 decreased from 21 to 12 Torr and remained less than 14 Torr for 1 h. Arterial pH declined from 7.40 to a nadir of 7.32 at 1 h. Mean plasma catecholamine concentrations rose promptly from a baseline of 524-546 pg/ml for norepinephrine (NE) and 156-235 pg/ml for epinephrine (E) to reach a peak at 15 min (NE = 2,476-3,276, p less than 0.01; E = 1,856-4,065 pg/ml, p less than 0.01) and remained elevated thereafter. Neither dose of naloxone significantly altered plasma NE or E concentrations. Therefore, we conclude that endogenous opiates do not modulate the sympathoadrenal response to moderately long periods of hypoxemia unaccompanied by acidemia.

Topics: Animals; Drug Synergism; Epinephrine; Female; Fetal Hypoxia; Hypoxia; Naloxone; Norepinephrine; Receptors, Opioid; Sheep

Endogenous opioids are released in great amounts in perinatal asphyxia. The role of this release has been unclear. In a study of cerebral blood flow and oxygen metabolism in 5 hypoxic newborn lambs, naloxone blocking of opioid receptors resulted in a proportional increase in telencephalic cerebral blood flow and oxygen metabolism. It is suggested that endogenous opioid release protects the neonatal brain in hypoxia by diminishing the cerebral metabolic rate of oxygen.

Topics: Animals; Blood Gas Analysis; Brain; Endorphins; Female; Fetal Hypoxia; Naloxone; Oxygen Consumption; Pregnancy; Sheep

Intravenous administration of the opioid receptor antagonist naloxone to asphyxiated fetal sheep increases the arterial blood pressure. We examined the hypothesis that endogenous opioids modify the cardiac output distribution during asphyxia due to changes in the vascular resistance of some fetal organs. Thirteen fetal sheep (0.8-0.9 of gestation) were chronically catheterized. Fetal asphyxia was induced by reducing the uterine blood flow with an inflatable occluder around the common internal iliac artery to approximately 50% of control for 40 min. Naloxone solution or the solvent alone was added for the last 20 min. Asphyxia caused hypertension, and the fetal arterial blood pressure further increased when asphyxiated fetuses received naloxone. Heart, brain, and adrenal blood flows increased due to the increase in blood pressure, with no changes in their vascular resistances. In contrast, kidney and carcass blood flows decreased, and their vascular resistances increased. We conclude that endogenous opioids inhibit the vasoconstriction of these vascular beds during fetal asphyxia.

Topics: Acid-Base Equilibrium; Animals; Blood Gas Analysis; Blood Pressure; Cardiac Output; Cardiovascular Physiological Phenomena; Endorphins; Female; Fetal Hypoxia; Fetus; Heart Rate; Naloxone; Pregnancy; Sheep

The effect of opiate receptor blockade on the plasma catecholamine response to hypoxemia was studied in seven chronically catheterized fetal lambs in utero. All animals underwent treatment with hypoxia alone, naloxone infusion alone (2 mg/kg) and hypoxia with naloxone at four different dosages (0.1, 0.5, 1.0, and 2.0 mg/kg). Maternal and fetal hypoxia was maintained for 20 min. There were no differences noted in the degree of hypoxemia or acidemia between the different hypoxia treatment groups. Hypoxia increased both norepinephrine and epinephrine plasma levels in all fetal sheep studied. We found a dose-dependent increase in plasma epinephrine levels in response to naloxone infusion during hypoxia. Plasma epinephrine level by 20 min of hypoxia with the 0.1 mg/kg naloxone dose (geometric mean 5366 pg/ml) was significantly more than with hypoxia alone (997 pg/ml). Naloxone at the other doses did not alter the epinephrine responses. There was no augmentation of plasma norepinephrine levels by naloxone at any dose studied. Thus, naloxone augmented the plasma epinephrine response to hypoxia in fetal sheep suggesting that the opiate peptides act as modulators of the sympathoadrenal system. The naloxone dose response differences observed in this study suggest this modulation is largely by antagonism of mu-receptors.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Epinephrine; Female; Fetal Hypoxia; Heart Rate; Naloxone; Norepinephrine; Pregnancy; Sheep

The cardiovascular and plasma catecholamine responses to hypoxemia following endogenous opioid blockade were evaluated in 18 late gestation fetal lambs (0.75-0.83 gestation) in utero. Hypoxemia was produced by progressive constriction of the umbilical cord with an inflatable silicone rubber cuff while fetal heart rate, blood pressure, and arterial blood gases were monitored. Fetal arterial blood samples were obtained for plasma catecholamine analysis using a radioenzymatic method. The animals were divided into 4 experimental groups. Control animals during normoxemia and following hypoxemia are represented by groups I and III, respectively. During umbilical constriction, arterial oxygen tension declined from 21.4 +/- 0.3 to 13.4 +/- 0.3 torr (p less than 0.001, mean +/- SE) and was accompanied by an increase in blood pressure (44 +/- 1 to 53 +/- 1 torr), decrease in heart rate (176 +/- 4 to 114 +/- 4 beats/min) and rise in plasma norepinephrine (437 +/- 90 to 3,410 +/- 617 pg/ml) and epinephrine (53 +/- 10 to 1,074 +/- 325 pg/ml). Naloxone infusion had no significant effect on the fetus during either normoxemic (group II) or hypoxemic conditions (group IV). Plasma catecholamines rose less in group IV than in hypoxemic control fetuses (norepinephrine: 2,407 +/- 406 vs. 3,410 +/- 617 pg/ml; epinephrine: 966 +/- 641 vs. 1,074 +/- 305 pg/ml), but the differences were not significant (p greater than 0.2). It is concluded that endogenous opioids do not play a major role in the modulation of cardiovascular and sympathoadrenal adaptations to moderate hypoxemia in the fetus.

Topics: Animals; Catecholamines; Constriction; Female; Fetal Blood; Fetal Hypoxia; Hemodynamics; Naloxone; Pregnancy; Receptors, Opioid; Sheep; Umbilical Cord

Topics: Animals; Blood Pressure; Endorphins; Female; Fetal Hypoxia; Heart Rate; Naloxone; Pregnancy; Sheep

Topics: Animals; Cats; Endorphins; Female; Fetal Hypoxia; Humans; Lung Diseases, Obstructive; Naloxone; Pregnancy; Rabbits; Respiration; Sheep