Edward J. Quilligan

Oxidative stress, brain white matter damage andintrauterine asphyxia in fetal lambs

In order to examine the role of oxidative stress in asphyxia‐induced perinatal braindamage, near‐term fetal lambs were subjected to umbilical cord occlusion for approximately 60 min until fetal arterial pH diminished to less than 6.9 and base excess to less than −20 meq/l. Thelevels of superoxide, hydrogen peroxide, glutathione (GSH) and thiobarbiturate‐reactivesubstances (TBARS) within brain grey and white matter were determined at 72 h to correlatewith morphological changes. Although the topography and extent of brain damage variedsomewhat from case to case, ranging from focal infarction in grey or white matter to subtle andpatchy alterations of white matter, the telencephalic white matter appeared to bear the brunt ofdamage as compared to other regions. The parietal white matter, in particular was often the seatof early pathological changes that could be seen in isolation. These white matter changes wereaccompanied by significant increases in hydrogen peroxide and TBARS levels as compared tothose in grey matter. In another set of experiments, 8 different brain regions were assayed forTBARS, GSH and superoxide dismutase (SOD). A highly significant rise in the levels of TBARSwas again noted in the parietal and frontal white matter. SOD levels were higher in the frontal andparietal white matter, basal ganglia and cerebellum. Cerebral cortical and hippocampal neuronswere relatively unaffected until accompanied by more severe damage to grey and white matter atother sites. These results suggest that the developing telencephalic white matter appears to bemost vulnerable to the effects of intrauterine fetal asphyxia and that oxidative stress may be amajor contributing factor in the pathogenesis of perinatal hypoxic–ischemic encephalopathy.

Obstetric characteristics and fetal heart rate patterns of infants who convulse during the newborn period

Seizure activity in the immediate neonatal period has been shown to correlate with long-term neurological handicap. The perinatal course of 34 term and 32 preterm infants who developed seizure activity in the neonatal period was compared to that of 66 matched control infants without neonatal seizure activity. The incidence of antenatal complications and abnormal fetal heart rate patterns and the percentages of abnormal labor, operative delivery, and low Apgar scores were significantly greater in the study infants than in the control infants. Earlier onset of seizure activity was seen in term versus preterm infants and term infants with abnormal versus normal fetal heart rate patterns. Management decisions regarding intervention or nonintervention based on fetal heart rate patterns were deemed appropriate in 31 of 34 term infants, yet short- and long-term neurological sequelae were significant.

Interferon responses in maternal and fetal mice.

The kinetics of maternal-fetal interferon and a chemical interferon inducer were studied in Swiss-Webster white mice at 8, 15, and 19 days of gestation. Crude interferon was administered by maternal tail vein injection to one group. There was no transfer of interferon to the fetus despite high maternal levels. A chemical interferon inducer (10-carboxymethyl-9-acridanone) was given intramuscularly to a second group. Both maternal and fetal interferon responses rapidly reached significant levels, although the fetal response was less than that of the mother. Presence of the inducer was demonstrated in both maternal and fetal samples, indicating placental transport of the chemical to the fetus. The implications of these findings for the fetal immune response are discussed.

Effects of Extracorporeal Membrane Oxygenation (ECMO) on Fetal Lambs

The purpose of this study was to determine the applicability of using ECMO techniques to support fetal oxygenation while maintaining fetal circulation in utero. Extracorporeal membrane oxygenation (ECMO) was applied to four chronically instrumented fetal lambs with the placental circulation intact. Blood was obtained through a catheter (2.5 mm ID) inserted into the right atrium and was returned to the carotid artery after oxygenation (V-A ECMO). The rate of blood flow varied from 200 to 300 mL/min (80-100 mL/kg/min). Compressed air at 2 L/min was used to ventilate the membrane, achieving the mean pO2 of 36.1 ± 9.5 torr in the blood after the membrane. A positive linear correlation was observed between pre-membrane and post-membrane pO2. Despite maternal hypoxia experimentally produced by reducing FiO2 of the mother for 15-35 min, V-A ECMO successfully maintained fetal blood pH and gases within the normal control range. These data indicate that V-A ECMO can effectively oxygenate lamb fetuses

Distribution of oxygenated blood flow at three different routes of extracorporeal membrane oxygenation in exteriorized fetal lambs

Objective: The purpose of this study was to determine which extracorporeal membrane oxygenation (ECMO) route best approximates the normal physiologic pattern of oxygenated blood distribution in fetal lambs submerged in warm saline solution.

Two sinusoidal heart rate patterns in fetal lambs undergoing extracorporeal membrane oxygenation.

OBJECTIVESnThe study analyzed the phase relationship between fetal heart rate and arterial blood pressure fluctuation during sinusoidal heart rate patterns in fetal lambs.nnnSTUDY DESIGNnThirty-two fetal lambs were placed on extracorporeal membrane oxygenation after cesarean delivery at ages ranging between 113 and 133 days gestation. Sinusoidal heart rate patterns persisting for >10 minutes were analyzed. The relationships between the sinusoidal heart rate cycles and the arterial blood pressure cycles were quantitatively expressed in degrees by timing the zenith and the nadir of each and assigning a phase-angle index (with 0 [360] and 180 degrees being synchronized and reciprocal, respectively). Simultaneous blood samples were taken from the 4 different sites of the fetal circulation for blood gas and acid-base analysis when the sinusoidal heart rate pattern appeared. Regional cerebral blood flow was determined by means of the colored microsphere technique in 8 fetuses with sinusoidal patterns and 7 control fetuses.nnnRESULTSnSinusoidal heart rate patterns were observed in 13 (40.6%) of the 32 fetal lambs. Two types of fetal heart rate and arterial blood pressure relationship could be recognized during sinusoidal pattern, the reciprocal type (n = 7) and the synchronized type (n = 9). A reciprocal type of sinusoidal pattern preceded a synchronized type pattern in 3 lambs that showed sinusoidal patterns at different stages of the experiment. The reciprocal type was associated with a higher baseline heart rate and amplitude of the sinusoidal heart rate pattern than was the synchronized type. The synchronized type was associated with a lower pH and base excess than was the reciprocal type. The cerebral blood flow in the medulla oblongata was significantly lower during the synchronized type pattern than during the reciprocal type pattern.nnnCONCLUSIONnThere are 2 types of sinusoidal heart rate pattern. A synchronized type sinusoidal heart rate pattern may indicate more advanced fetal compromise than is associated with a reciprocal type pattern.