Bioeffects of diagnostic ultrasound on auditory function in the neonatal lamb.
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Animals↗
Biomedical subjects
M A Plessinger
Publications and source records attributed to M A Plessinger.
Effect of alpha 1 receptor blockade upon maternal and fetal cardiovascular responses to cocaine.
Previous studies in pregnant ewes have demonstrated that intravenous (IV) cocaine produces increased maternal blood pressure and vasoconstriction of the uterine arteries, resulting in decreased uterine blood flow and decreased fetal oxygen levels. To determine whether these responses to cocaine were mediated by alpha 1-adrenergic receptor stimulation, cocaine was administered to four pregnant ewes before and after phenoxybenzamine hydrochloride, an alpha 1 receptor antagonist. Before phenoxybenzamine infusion, cocaine 2.0 mg/kg produced a 53% increase in maternal mean arterial pressure (MAP), a 50% reduction in total uterine blood flow, and a 191% increase in uterine vascular resistance. Cocaine also increased fetal MAP by 24%, increased the fetal heart rate (FHR) by 51%, and reduced fetal PO2 by 29%. Alpha 1 receptor blockade after phenoxybenzamine 5.0 mg/kg was confirmed by a lack of change in uterine blood flow to IV norepinephrine 30 micrograms before cocaine administration. After phenoxybenzamine, cocaine produced no increase in maternal or fetal MAP. However, total uterine blood flow decreased 44%, uterine vascular resistance increased 59%, FHR increased 36%, and fetal PO2 fell 18%. Because the fetal responses mimicked the maternal responses to cocaine both before and after phenoxybenzamine, phenoxybenzamine apparently crossed the placenta to block fetal alpha 1 receptors as well. Alpha 1-adrenergic receptor stimulation is the major mechanism for the maternal and fetal hypertensive responses to cocaine. Although cocaine produces uterine artery vasoconstriction primarily by alpha 1 adrenergic receptor stimulation, its vasoconstrictive effects may involve other vasoactive neurotransmitters, such as dopamine or serotonin.
Animals↗
Prenatal cocaine exposure to the fetus: a sheep model for cardiovascular evaluation.
Transplacental passage of cocaine in response to maternal administration of intravenous (IV) cocaine in doses of 1.0 and 2.0 mg/kg was studied in 6 pregnant ewes and fetuses and correlated with maximum changes in maternal and fetal blood pressures (BP), heart rates (HR) and fetal arterial blood gas values. Certain animals were given larger doses (3.0 and 5.0 mg/kg) of cocaine to examine cocaine-related cardiopulmonary and neurologic sequelae. Cocaine was extracted on C-18 sorbent columns and analyzed by gas chromatography. At 1.0 and 2.0 mg/kg, cocaine produced dose-dependent increases in maternal HR and BP which were maximum by 1 minute. The fetal response was characterized by maximum increases in BP and decreases in PO2 by 3 minutes and increases in HR by 15 minutes. Cocaine rapidly appeared in the fetal circulation, was approximately 15% of maternal concentrations by 5 minutes, and was undetectable in both circulations by 60 minutes. At cocaine doses of 3.0 and 5.0 mg/kg significant maternal cardiopulmonary and neurologic complications were encountered including bradyarrhythmias, respiratory distress, seizure and death. These data indicate that cocaine exerts direct drug actions upon maternal cardiovascular and neurologic function. In addition, cocaine affects fetal cardiovascular function directly via transplacental passage and indirectly by fetal hypoxemia from cocaine-induced uterine artery vasoconstriction. (NIDA 04415)
Animals↗
Fetal sensory sequencing: applications of evoked potentials in perinatal physiology.
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Animals↗
Ultrasound effects on fetal auditory brain stem responses.
The use of diagnostic ultrasound raises questions regarding its bioeffects upon fetal auditory function. This study was designed to determine whether ultrasound produces changes in the auditory brain stem response in fetal lambs. Near-term fetal lambs were chronically instrumented with electroencephalogram electrodes at the vertex and the right mastoid region. An earphone was secured in the fetal right external ear canal for auditory stimulation. An ATL mechanical sector scanner was used for all ultrasound studies at a spatial peak, temporal average intensity of 15.5 mW/cm2. Auditory brain stem responses were recorded at five and 15 minutes during pulsed-wave ultrasound exposure of the cranium and then 30 minutes after cessation of insonation. Sham experiments (without insonation) were then performed in a similar time sequence to rule out the effects of habituation. There was a consistent decrease in the mean amplitude and a consistent increase in the mean latency of all five wave deflections of the auditory brain stem response during insonation. These changes persisted for 30 minutes following cessation of insonation, after which auditory brain stem response amplitude and latency values returned toward control values. No changes in auditory brain stem response amplitude or latency were observed during sham experiments. We conclude that direct ultrasound exposure of the fetal cranium through the maternal abdominal wall may temporarily influence nerve conduction along central nervous system axonal pathways. This transient influence is reversible, with all values approaching baseline within 30 minutes.
Animals↗
Effect of cocaine on uterine blood flow and fetal oxygenation.
Five pregnant ewes and their singleton fetuses were instrumented at 115 to 120 days' gestation (term, 145 days) for heart rate, blood pressure, uterine blood flow, and arterial blood gas sampling. In separate studies, cocaine was given to the ewe or fetus as a 0.5-, 1.0-, or 2.0-mg/kg intravenous bolus, and cardiovascular and arterial blood gas values were obtained for 60 minutes after the injection. The results showed that maternal administration of cocaine produced dose-dependent increases in maternal blood pressure and decreases in uterine blood flow. Uterine vascular resistance increased by 52%, 96%, and 168%, respectively. These responses were accompanied by marked fetal hypoxemia, hypertension, and tachycardia. Direct cocaine administration to the fetus produced smaller increases in fetal heart rate and blood pressure than those observed following maternal cocaine injection, and no significant changes in fetal arterial blood gas values. The conclusions are cocaine alters fetal oxygenation by reducing uterine blood flow and impairing oxygen transfer to the fetus; and fetal cardiovascular changes to maternal administration of cocaine may reflect fetal hypoxemia, increased fetal levels of cocaine or fetal catecholamines, or a combination of these events.
Animals↗
Fetal auditory brain stem response: effect of increasing stimulus rate during functional auditory development.
The fetal auditory brain stem response to increasing stimulus rates of 16, 32, 45, 64, 87, and 100 clicks/sec were determined in eight fetal lambs of 115 to 136 days' gestation (term = 145 days). To conduct these studies, a hysterotomy was performed on the pregnant ewe at 110 to 118 days' gestation to implant stainless steel electrodes in the fetal scalp and a hearing aid receiver in the fetal external ear canal. The fetus was returned to the uterus and the pregnancy was allowed to continue. Auditory brain stem responses from younger fetuses (115 to 125 days' gestation) were present at the slower click rates but were not observed consistently at the fast click rates until the fetuses were older (125 to 136 day's gestation). Latency values of the auditory brain stem response peaks decreased with increasing fetal age and increased with increasing stimulus rates. From a two-way analysis of variance, the influence of age and click rate alone and more important, the interaction of age and click rate were determined to have highly significant effects (p less than 0.001) on latency values of wave 1, wave V, and central conduction time. These auditory brain stem response results suggest that the cochlear component of the fetal auditory system undergoes rapid change in late gestation to process incoming stimuli at a faster rate.
Acoustic Stimulation↗
Fetal auditory brain stem response: external and intrauterine auditory stimulation.
Singleton fetuses from five pregnant ewes of 120-129 days gestation (term = 145 days) were tested for fetal auditory brain stem responses (ABR) generated by earphones placed on the maternal abdomen and compared with ABRs generated by an earphone secured in the fetal lamb's ear. To conduct these studies a cesarean section was performed on the pregnant ewe at 105-110 days gestation in order to implant stainless steel electrodes in the fetal scalp and a hearing aid receiver in the fetal external ear canal. The fetus was returned to the uterus, and the pregnancy was allowed to continue. Comparison of the externally elicited fetal ABR with the internally elicited fetal ABR indicates similar response patterns with delayed peak latencies observed in ABR responses from external stimulation. This new method of generating fetal ABRs by an external sound source documents the neurological response of the fetal auditory end organ and the fetal brain stem in the pregnant nonstressed animal model and may have applications in developmental studies of the fetal auditory system.
Acoustic Stimulation↗
The fetal visual evoked potential.
Five singleton fetal lambs were surgically instrumented at 110-121 days gestation (term gestation = 145 days) for measurement of visual evoked potentials (VEP) in utero. Light flashes were generated by a small incandescent bulb secured under the right fetal eyelids and the visual responses were recorded through stainless steel electrodes implanted in the fetal scalp. Four of the five fetal lambs were surgically instrumented between 110-113 days. VEPs recorded in these four animals from 111-114 days exhibited N1, P1, and N2, but lacked the P2 component. All VEP components (N1, P1, N2, P2) were measureable by 115-118 days in these fetuses. One fetus was surgically instrumented at 121 days and VEPs containing all components were measurable until 125 days gestation when the equipment dislodged in utero. Serial VEP recordings from all five fetal lambs from 111-128 days indicated no change in latency to N1 while significant latency changes occurred in P1, N2, and P2 suggesting maturational development of the visual system. Histological assessment of the eyes from three animals at delivery revealed only thickening and increased vascularity of the cornea in response to the light source resting on the fetal eye. In conclusion, these results suggest that the fetal visual evoked potential has application in the longitudinal study of normal visual development in utero and offers a technique for studying visual response changes to adverse perinatal events.
Animals↗
Effect of graded reductions in uteroplacental blood flow on the fetal lamb.
Graded reductions in uteroplacental blood flow (UBF), produced by an externally adjustable vascular occluder, were studied in unanesthetized pregnant sheep. This method was designed to simulate the physiological occurrence of reduced UBF to study its effects on fetal status. Sheep were divided into four groups in which average percent changes (+/- SE) in UBF, as measured by electromagnetic flow probes, were 7 +/- 2, -24 +/- 1, -49 +/- 1, and -63 +/- 2% for 1 h. Maternal and fetal cardiovascular (heart rate and blood pressure) and blood gas measurements of PO2 and PCO2, pH, and O2 content were determined before, during, and after recovery from UBF reduction. UBF reduction had no significant effect on maternal measurements. Changes in fetal PO2 and O2 content were directly related to the extent of vascular occlusion (P less than or equal to 0.05). Fetal pH markedly decreased after 1 h of 49% UBF reduction (P less than or equal to 0.05) and within 10 min after 63% UBF reduction (P less than or equal to 0.05). Fetal bradycardia (P less than or equal to 0.05) resulted from 63% reduction in UBF. Fetal heart rates at recovery were greater than base-line heart rate values (P less than or equal to 0.05) in the three groups whose UBF was restricted. The results of the present study suggest that the uterus of the pregnant ovine is perfused in sufficient excess to protect the fetus during short-term reductions of less than 50% UBF.
Animals↗
The fetal auditory brain stem response: serial measurements at two stimulus intensities.
Eleven fetal lambs were tested for auditory brain stem responses (ABRs) at 105 and 90 db sound pressure level from 110 to 116 days until 133 days gestation. ABRs were elicited in response to 1200 clicks, presented at 16 clicks/sec, from a hearing aid receiver secured in the fetal external ear canal and recorded from subdermal stainless steel electrodes at the vertex (active electrode) and anterior pinna (reference electrode). Six term newborn lambs were tested similarly for ABR comparison. No fetal ABRs appeared before 117 days gestation. Thereafter, the ABRs exhibited decreasing peak latencies with increasing stimulus intensity and fetal age. Newborn ABR latency measurements were compared with predicted newborn values generated from linear regression analysis of fetal data. Newborn latencies to waves I and II approximated predicted values. Newborn latencies to waves III, IV, and V were much shorter than predicted, suggesting rapid maturation of higher brain stem and midbrain neurogenerators during late fetal development.
Animals↗
Fetal auditory brainstem evoked response (ABR).
Auditory brainstem evoked responses (ABRs) were obtained in utero from five fetal lambs instrumented between 108 and 124 days gestation and tested from 2 to 24 days following surgery. The fetal ABR patterns were then compared with similar ABR measurements from term newborn lambs at 1 day of age. The characteristics of the preterm fetal ABR were dependent upon the period of gestation in which the testing was conducted. The fetal ABR is absent prior to 117 days gestation. The earliest recorded fetal ABR consisted of one or more reproducible deflections and was observable by day 117-125 of gestation. By 126 days gestation the ABR was comparable in waveform pattern to those obtained in one day old term newborn lambs but with delayed peak latencies. The most definitive characteristic of the fetal ABR was the interpeak latency between waves IV and V, which was greater than the interpeak latencies between other wave deflections. Serial recordings of fetal ABRs indicate that latencies to each wave decrease with advancing gestational age. These changes may be suggestive of a maturational process within the auditory system of the developing fetus.
Animals↗
Effects of zidovudine (AZT) and dideoxyinosine (ddI) on human trophoblast cells.
The anti-HIV agents AZT (zidovudine) and ddl (dideoxyinosine) are being used clinically during pregnancy. The toxicity of these agents to the fetus and placenta remains a concern because few human pregnancy exposure data are available, and pregnant rodent studies with AZT indicate increased embryonic resorptions and developmental arrest. The current study used a human choriocarcinoma cell line (JAr), which exhibits many characteristics of the early placenta, to assess the effects of a single 24 h exposure of 7.6 or 0.076 mM AZT, and the effects of a single 24 h exposure of 7.6 or 0.076 mM ddI upon cell proliferation and hormone production of human chorionic gonadotropin (hCG), estradiol (E2), and progesterone (P4). The higher concentration of AZT and ddI produced significant (P < 0.025) reductions in cell numbers and growth rate while producing significant increases in hormone production (hCG, E2, and P4). The lower concentration of AZT and ddI produced significant increases in E2 production, but no changes in cell numbers, hCG, or P4. Because placental cells require androgen precursor for E2 synthesis, exogenous androstenedione was added to confirm observations of increased estradiol synthesis after AZT or ddl exposure. These results demonstrate that single 24 h high dose exposures of AZT or ddI produce significant inhibition of cell proliferation and alterations in hormone production in this paradigm of human placental cells.
Androstenedione↗